Xiaojie Wang, Jamie Lo, Colin Studholme, Zheng Liu, Christopher Kroenke

In utero diffusion and anatomical MRI measurements were performed on a naturally occurring intrauterine growth restriction (IUGR) and 3 control pregnant rhesus monkeys. Water diffusion anisotropy (FA) within fetal cerebral cortex as well as white matter was used to characterize abnormal development in the IUGR fetal brain. Markedly higher cortical FA, indicating aberrent morphogenesis of cortical neurons, was observed in the IUGR fetal brain compared to controls. In addition, significantly reduced FA in a number of white matter tracts was also found in the IUGR fetal brain, reflecting perturbed white matter development.

Marin Nishio, Yuji Komaki, Fumiko Seki, Junichi Hata, Akiko Uematsu, Ryutaro Yano, Ryosuke Ishihara, Erika Sasaki, Hideyuki Okano, Akira Furukawa

MTR reflects the protein content such as myelin of brain. We examined the age-related MTR for common marmosets (1-18 months). Almost all regions of the brain have increased as T1 relaxation similar curve and the rate change of the MTR in each region was different. In voxel-wise analysis, MTR increase shows back-to-front maturation patterns in white matter. This pattern has observed in human studies. MTR can be a good marker to evaluate the normal brain development of common marmoset, and eventually a suitable parameter to assess brain developmental disorders for study, diagnosis, and treatments.

Aneurin Kennerley, Devashish Das, Fiona Boissonade, Milena De-Felice

This study uses multi-parametric MRI measures to further our understanding on the pathophysiology of migraine in a novel preclinical model of medication overuse headache. Rats undergo sustained triptan exposure inducing cutaneous allodynia. Following drug exposure, we perform ASL, NMR, connectivity and evoked response BOLD fMRI to investigate sustained neuronal adaptations/changes. We investigate how drug overuse leads to latent sensitization to migraine triggers 20 days after exposure.  We find significantly altered CBF levels in triptan treated animals. NMR reveals changes in GABA & Tau metabolite levels. fMRI shows changes in functional connectivity and activation of brain regions associated with pain pathways.        

Jacob Ellegood, Benjamin Darwin, Matthijs Van Eede, Mark Henkelman, Jason Lerch

Examination of lateral asymmetry differences in mouse models related to Autism.  Using 42 different mouselines as a representative sample of an autistic population, we show a loss of asymmetry in the mutant mice compared to wild-type that may be indicative of functional and/or behavioural variations.

Min Hui Cui, Sandra Suzuka, Mary Fabry, Seetharama Acharya, Henny Billett, Craig Branch

The effect of congenital anemic hypoxia on brain energy metabolism was studied on BERK-Hemi mouse exhibiting poor oxygen delivery secondary to reduced hemoglobin oxygen affinity. Regionally increased CBF in BERK-Hemi mouse was correlated with decreased mean diffusivity and tissue T1. Additionally, BERK-Hemi mouse exhibited elevated concentrations in N-acetylaspartate, glutamate, total choline and glucose in thalamus, but a lower concentration of glutamine.  Together, the results suggest BERK-Hemi mice develop a compensatory mechanism which leads to increased glycolysis to combat hypoxia and increased reactive oxygen stress. 

Benjamin Lemasson, Nora Collomb, Alexis Arnaud, Florence Forbes, Emmanuel Barbier

Brain tumor heterogeneity plays a major role during gliomas growth and for the tumors resistance to therapies. The goal of this study was to demonstrate the ability of clustering analysis applied to multiparametric MRI (mpMRI) data to summarize and quantify intralesional heterogeneity during tumor growth. A mpMRI dataset of rats bearing glioma was acquired during the tumor growth (5 maps, 8 animals and 6 time points). After co-registration of every MR data over time, a clustering analysis was performed using a Gaussian mixture distribution model. Although preliminary, our results show that clustering analysis of mpMRI has a great potential to monitor quantitatively intralesional heterogeneity during the growth of tumors. 

Alexandru Korotcov, Asamoah Bosomtwi, Andrew Hoy, Daniel Perl, Nathan Cramer, Xiufen Xu, Clarke Tankersley, Zygmunt Galdzicki, Bernard Dardzinski

MRI is a useful technology for longitudinal assessments, which are critical for understanding vascular changes in the brain. Exposure to high-altitude (HA), hypoxic conditions, e.g. by military personnel, can result in physiological changes and ultimately degradation of neurobehavioral performance. We utilized in vivo MR imaging in mice to examine changes in brain vasculature, myelination and structure and to provide longitudinal insights into pathological changes caused by long-term exposure to HA. We observed changes in T2 that reflect edema/inflammation, fractional anisotropy changes that suggest changes in white matter myelination, and rCBF and VDi imaging indicating adaptations to HA conditions. 

Claudia Green, Anuka Minassian, Andreas Beyrau, Stefanie Vogel, Michael Diedenhofen, Melanie Nelles, Dirk Wiedermann, Mathias Hoehn

In this study we combined rs-fMRI and diffusion MRI to assess the therapeutic capacity of cortically injected human neural stem cells in the mouse brain after stroke during 3 months. Seed-based analysis of diffusion anisotropy maps and functional connectivity were conducted interrelated with the main focus on the effect of stroke and treatment on the contralesional hemisphere. A delayed breakdown in functional network strength for the therapeutically treated group compared to a sham treated group is observed. However, diffusion anisotropy parameters stay stable with an increasing trend for the thalamus. 

Dandan Zheng, Baohong Wen, Baoqiong Zhao, Jingliang Cheng

Stroke is the third leading cause of death in industrialized countries and the most frequent cause of acquired adult. Butylphthalide has been shown to have protective effects against ischemic stroke. This study would like to observe the temporal evolution of parameters calculated by IVIM model in an experimental middle cerebral artery occlusion (MCAO) rat model, and how the butylphthalide effect the physiological changes.

Jennifer Lefeuvre, Wen-Yang Chiang, Nicholas Luciano, Cecil Yen, Mathieu Santin, Stéphane Lehéricy, Steve Jacobson, Afonso Silva, Daniel Reich, Pascal Sati

When induced to have experimental autoimmune encephalomyelitis (EAE), marmosets can suffer from motor and sensory deficits highly suggestive of lesions located in the spinal cord. In this study, we developed an in vivo spinal cord imaging protocol at 7T for marmosets, and were able to visualize gray and white matter as well as focal EAE lesions. Future work will focus on characterizing the spatiotemporal evolution of spinal cord EAE lesions over the disease course.

Zheng Liu, Martha Neuringer, John Erdman Jr., Matthew Kuchan, Laurie Renner, Emily Johnson , Christopher Kroenke

Infant rhesus macaques were studies to test the effects of breastfeeding versus formula-feeding on cerebral cortex maturation. Through analysis of structural and diffusion MR images, brain volume over the first 6 months of life was not significantly altered by formula-feeding versus breastfeeding, or by formula lutein supplementation. However, cellular maturation within cerebral cortical gray matter differed between formula-fed and breastfed animals. Lower gray matter FA of breastfed infants is interpreted to reflect greater neuronal arborization. This difference may be related to the different social experience as well as the nutrient composition of breast milk.

Yu-Chieh Kao, Chia-Feng Lu, Huai-Lu Chen, Ping-Huei Tsai, Fei-Ting Hsu, Hua-Shan Liu, Gilbert Aaron Lee, Paul Blakeley, Li-Chun Hsieh, Bao-Yu Hsieh, Cheng-Yu Chen

An experimental model of mild traumatic brain injury (mTBI) mimicking the pathological outcomes in mTBI patients found in motorcycle accident was developed. The longitudinal behavioral and imaging assessment showed the functional deficit but intact brain structure in our model, which could be further used to explore early fluid and image biomarkers for mTBI

Kurt Bockhorst, Juan Herrera, Shakuntala Kondraganti, Jarek Wosik, Ponnada Narayana

Some of the gadolinium based contrast agents are shown to produce enhancements on T1-weighted images long after their administration in certain brain structures in humans, raising questions about the safety of these agents. The enhancement is thought to be due to dechelation of the contrast agents.  Understanding the pathophysiological effects requires systematic pre-clinical studies.  As a first step towards this goal we conducted longitudinal in vivo studies in rodents administered Magnevist and Omniscan for ten days to quantify the temporal profile of enhancement using relaxometry and investigate if this enhancement has an effect on the tissue microstructure. Our results show that Ominiscan lowers both T1 and T2 starting from week 2 post contrast administration. However, such changes were not observed in Magnevist and saline treated animals.  The contrast agents do not appear to have significant effect on any of the DTI measures.

Lindsay Cahill, Jonathan Bishop, Lisa Gazdzinski, Adrienne Dorr, Bojana Stefanovic, John Sled

A longitudinal study employing continuous arterial spin labelling MRI with a hypercapnic challenge was used to examine changes in cerebral blood flow with physical exercise in healthy, adult mice. We found that exercise resulted in increases in the normocapnic and hypercapnic blood flow in the hippocampus and that these changes were positively correlated to the volume of the hippocampus following exercise. Interestingly, hypercapnic hippocampal blood flow prior to exercise was predictive of the distance subsequently run and exposure to this voluntary exercise regime was found to reduce these pre-existing blood flow differences. 

Alexandra Petiet, Mathieu Santin, Elodie Laffrat, Romain Valabrègue, Thomas Samoyeau, Stéphane Hunot, Stéphane Lehéricy

Parkinson’s disease (PD) is characterized by neurodegeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNc). The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin can induce Parkinson syndrome in primate models. We evaluated the nigrostriatal (NS) pathway degeneration in MPTP Squirrel monkeys using diffusion MRI. The results showed significantly increased fractional anisotropy in all NS regions of the MPTP group (SN, caudate and putamen regions). Axial diffusivity also significantly increased in the SN and caudate regions, while radial diffusivities did not show any differences, except a significantly decreased λ3 in the putamen. Those results should help develop preclinical evaluation of PD therapeutics.

Anna Mechling, Kirsten Kleim, Tanzil Arefin, Hsu-Lei Lee, Thomas Bienert, Jürgen Hennig, Dominik von Elverfeldt, Brigitte Kieffer, Laura-Adela Harsan

Mu opioid receptor (MOR) knock-out Oprm1^-/- mice exhibit deficits in social behavior and repetitive behavior, which are phenotypes related with autism spectrum disorders (ASD). Thus, MOR deficient mice were recently proposed as monogenic models of ASD. Moreover, a decrease in metabotropic glutamate receptor 4 (mGluR4) levels was found in these mice. A treatment with VU0155041, an allosteric modulator of mGluR4, reversed behavioral deficits in Oprm1^-/- mice. Here, we investigated the remodeling on brain connectivity level in Oprm1^-/- mice under VU0155041-treatment and found enhancement of positive correlation towards frontal brain areas involved in reward-processing due to the compound.

Cecil Yen, Wen-Yang Chiang, Afonso Silva

The common marmoset, a small New World primate, is a popular non-human primate for transgenic lines of brain disease models and 3D printed helmets to immobilize the head for awake MRI. However, cerebral blood flow (CBF), a crucial component to normal brain functions, has not been measured to date in awake marmosets. In this study, we demonstrate the feasibility of measuring whole brain CBF in the awake marmoset using a continuous arterial spin labeling MRI sequence and dedicated hardware, comprising of a spin-labeling coil and a novel 10-channel phased array in a 7T animal MRI system.

Cuijin Lao, Jiawei Chen, Li Wang, Gang Li, Dinggang Shen

Accurate segmentation of monkey brain MRI is of great importance in studying the brain development, pathogenesis and progression of neurological diseases. However, it is challenging for automatic segmentation due to noise, low contrast and partial volume effect. Existing tools fine-tuned to human brain MRI are ineffective for monkey brain MRI  due to their difference from human brain MRI. In this study, we propose a machine learning-based framework for the segmentation of monkey brain MRI into skull, cerebellum, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) of the cerebrum. The experiment results demonstrate that our proposed method outperforms than previous methods. 

Jasmien Orije, Geert De Groof, Elisabeth Jonckers, Sander Raymaekers, Marleen Verhoye, Veerle Darras, Annemie Van der Linden

The effect of thyroid hormones on seasonal neuroplasticity in adult songbirds was never investigated before. To study this we treated photorefractory starlings with methimazole, which resulted in a depletion of thyroid hormones plasma levels. Using repeated measures of in vivo DTI and song recordings, neuroplasticity and song behaviour were monitored over different photoperiods. We found indications that thyroid hormones can modulate the seasonal neuroplasticity both directly at the level of the song control system, as suggested by direct changes in song behaviour after methimazole-treatment, and indirectly via the hypothalamus-pituitary-gonad axis, as methimazole-treatment inhibited the testosterone increase upon photostimulation.

Sun Young Chae, Geun Ho Im, Moon-Sun Jang, Won-Beom Jung, Jung Hee Lee

Physical exercise is known to boost the spontaneous recovery, but the exact mechanism for exercise induced recovery after brain injury is not clearly known. In this study, we show enhanced neuroplasticity with physical exercise on the intact side as well as the damaged side for the HI injured rat brain by calculating the brain activation maps from BOLD-fMRI: Increased inter-hemispheric transfer and intra-hemispheric extension of activated areas were observed with physical exercise covering the widespread sensory-motor related areas in the contralesional hemisphere.

Adnan Bibic, Thea Sordia, Erik Henningsson, Linda Knutsson, Freddy Ståhlberg, Ronnie Wirestam

In this study, an improved quantification approach for measuring ASL transit-time parameters is proposed. The concept is based on multi-TI ASL measurements, where the dynamics of the inverted spins are described by the Fokker-Planck equation. The random forces in this equation are assumed to occur due to pseudo-diffusion in the capillaries and subsequent filtration through the blood brain barrier (BBB). The obtained time for the intravascular water to distribute from arteries through the capillary bed and into the parenchyma can, for example, be related to the capillary function as well as to the integrity of the BBB.

Nina Nagelmann, Frauke Freisfeld, Robin Schubert , Sarah Schramke, Verena Schuldenzucker , Lorena Rieke, Tamara Matheis, Harald Kugel, Ralf Reilmann, Cornelius Faber

Huntington’s Disease (HD) is a fatal neurodegenerative disorder, caused by a single genetic mutation, and characterized by deficits in motor coordination, behavior and cognition. A transgenic minipig model of HD has been established. Here, we employ single voxel MRS at 3 T to acquire metabolic profiles from the brain of this model over four years. We show that seven metabolite combinations can be quantified in adolescent and adult minipigs. Pathologic alterations in the phenotype were not observed at the age studied.

Xiaojie Wang, Colin Studholme, Natali Newman, Matthew Ford, Kathleen Grant, Christopher Kroenke

To assess the impact of first-trimester ethanol consumption on rhesus macaque fetal brain development, we employed anatomical and diffusion MRI to characterize macroscopic as well as cellular-level changes in ethanol exposed fetuses relative to controls at gestation days (G) 110 and G135. At both time points, perturbed brain maturation indicated by decreased brain volume, cortical surface area, and folding was seen in the ethanol exposed group. In addition, a trend for higher cortical water diffusion anisotropy seen in ethanol exposed group at G110 indicates abnormal dendritic differentiation. 

Xiaojie Wang, Zheng Liu, Colin Studholme, Christopher Kroenke

In utero T2-weighted (T2W) and diffusion MR images were acquired from control rhesus macaque fetuses at gestation days 85, 110, and 135. High-resolution T2W volumes and diffusion MR volumes were reconstructed using retrospective motion-correction techniques. Population-averaged T2W templates and fractional anisotropy (FA) templates were generated for each time point. Development of fetal tissue zones and gyrification of cerebral cortex were assessed using the T2W templates. In addition, morphogenesis of cortical neurons and maturation of white matter tracts were also characterized using the FA templates. 

Ryuta ITO, Atsuko YAMAMOTO, Shigehiro MORIKAWA, Kiyoshi MURATA

We assessed whether ultrasmall superparamagnetic iron oxide (USPIO) phagocytosed by microglia contribute to tumor enhancement in MR imaging of N-ethyl-N-nitrosourea (ENU)-induced endogenous rat brain gliomas by comparing MR images with the corresponding histological sections. USPIO-enhanced MR imaging may provide pure vascular bed images in the early phase within 6 hours after intravenous administration of USPIO agent because it was histologically proved that the administrated agent remained within intravascular space. In the late phase at 63-66 hours after the administration, USPIO-enhanced Gradient-Recalled-Echo T2-weighted images may depict the distribution of microglia that were magnetically labeled by USPIO agent.

Ravi Rungta, Bruno-Félix Osmanski, Davide Boido, Mickael Tanter, Serge Charpak

Optogenetics is increasingly used to map brain activation using techniques that rely upon functional hyperemia, for example opto-fMRI.  Here we demonstrate that light stimulation protocols similar to those commonly used in opto-fMRI increase blood flow in mice that do not express light sensitive proteins.  These results impose careful consideration on the use of photo-activation in studies involving blood flow regulation and suggest light could be used as a technical or therapeutic tool to locally increase blood flow in a controlled fashion.

Jeongchul Kim, Richard Bacus, Youngkyoo Jung, Christopher Whitlow

Translational research models using brain MRI to study non-human primates (NHPs) can provide insight into normal/abnormal human neurodevelopment. In particular, voxel-wise longitudinal imaging designs can characterize the trajectory of change in brain structure among individual subjects.  This study analyzes morphometric changes among a cohort of rhesus monkeys during late infancy, revealing total brain volume decreases driven by local volumetric contraction in frontal, parietal and temporal lobes. Characterizing NHP neurodevelopment may facilitate our understanding of complex normal and delayed human brain development, and provide a model to evaluate the influence of postnatal experiences on brain structure, cognitive ability and social behaviors.

Stephen Sawiak, Y Shiba, L Oikonomidis, C Windle, G Cockcroft, E Bullmore, A Roberts

Understanding the development of brain circuits through infancy to adulthood is crucial in determining the causes of mental health disorders, half of which are established before early adulthood. We use MRI to track the development of >200 discrete brain regions in a longitudinal primate brain study of 41 marmosets. Tensor-based morphometry indicated key regions of myelination from 3-6 months of age, and clustering of growth trajectories fitted with cubic splines allowed parcellation of regions based on growth patterns. We present maps of development showing differing patterns and rates of growth not only across lobes but between primary and associative areas.

Akiko Uematsu, Junichi Hata, Yuji Komaki, Fumiko Seki, Chihoko Yamada, Erika Sasaki, Hideyuki Okano

We investigated typical hippocampal development of a non-human primate model, common marmoset, using longitudinal DTI metrics data. Our findings showed dynamical non-linear developmental changes of hippocampal volume, MD and RD especially in its anterior part and suggested its neural turning point would be at puberty. These findings would give insights of disorder and disease of onset specific to developmental period.

Holly Holmes, Orlando Aristizabal, Oghale Obaro-Best, Estefania Gallego, Hari Rallapalli, Daniel Turnbull

Manganese-enhanced MRI (MEMRI) is a powerful technique for imaging rodent neuroanatomy. We investigated differences in the uptake of paramagnetic manganese ions (Mn²⁺) in the mouse brain at two postnatal days: P7 and P21. We observed higher uptake of Mn²⁺ in all neuroanatomical regions-of-interest (ROIs) at P7; this increased uptake was reflected in the shorter T1 times at P7 relative to P21. We also observed faster clearance of Mn²⁺ within the ventricles at P21. Our findings highlight the spatiotemporal differences in Mn²⁺ uptake and may be useful when planning MEMRI studies in the developing mouse brain.

Fumiko Seki, Yuji Komaki, Junichi Hata, Akiko Uematsu, Erika Sasaki, Keigo Hikishima, Hideyuki Okano

The postnatal brain development at the macroscale in common marmoset has been studied based on the volume measurement, as is not well-studied despite its importance. Maximizing the feature that it takes only 2 years to reach adulthood, the longitudinal MRI was conducted for 23 subjects. The volume of gray matter was inverted U curve trajectories, while increase of white matter became stable around 12 months old. Developmental patterns of regions in cerebral cortex were similar to gray matter but different in developmental timing. The study can demonstrate overall growth patterns were similar to patterns previously reported in humans and other monkeys.

Douglas Peters, Carson Purnell, Michael Tobia, Qing Yang, James Connor, Mark Meadowcroft

We show that there are observable VBM changes in white matter and grey matter fractions of an aging mouse and these changes are attenuated with a lipophilic high iron diet.  This data support the hypothesis that regressive white matter degeneration may be prevented with increased access to CNS iron.  Animals that do not have brain iron overloading show longitudinal white matter changes not observed in the iron loaded animals.  Furthermore, our data supports the white matter retrogenesis model observed in the aging human brain.

Marina Khodanovich, Irina Sorokina, Valentina Glazacheva, Andrey Akulov, Alexandr Romashchenko, Tatyana Tolstikova, Lilia Mustafina, Vasily Yarnykh

A recently developed quantitative MRI method, fast macromolecular proton fraction mapping (MPF) has shown a promise as a biomarker of myelin in human and animal studies with a particular advantage of sensitivity to grey matter (GM) demyelination. This study aimed to histologically validate the capability of MPF mapping using the cuprizone demyelination model. MPF strongly correlated with quantitative histology in all animals (r=0.95, p<0.001) as well as in treatment and control groups taken separately (r=0.97, p=0.001 and r=0.95, p=0.003, respectively). Close agreement between MPF and histology suggests that fast MPF mapping enables robust and accurate quantitative non-invasive assessment of demyelination.

Jörg Mauler, Karl-Josef Langen, Andrew Maudsley, Omid Nikoubashman, Christian Filss, Gabriele Stoffels, N. Shah

The specificity of MR based diagnosis of gliomas may be improved by O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake measured with PET and metabolite changes obtained from simultaneously acquired volumetric MR spectroscopic imaging. In order to cope with low SNR of the metabolites, the MR spectra of 25 patients were subject-specifically averaged within the tumour borders transferred from FET PET and compared to non-affected white matter of the contra lateral side. Strongest signal drops were found for GLU (0.58±0.43, WHO II) and NAA (0.33±0.13, WHO II-IV), strongest increase for CHO/NAA (3.9±2.4). The metabolite changes showed no dependency on tumour grade.

Fumiyuki Yamasaki, Yasuyuki Kinoshita, Satoshi Usui, Takeshi Takayasu, Ryo Nosaka, Manish Kolakshyapati, Taiichi Saito, Kazuhiko Sugiyama, Kaoru Kurisu

MRS and DWI of germinoma

Eric Kostelich, Erica Rutter, Tracy Stepien, Barrett Anderies, Jonathan Plasencia, Eric Woolf, Adrienne Scheck, Gregory Turner, Qingwei Liu, David Frakes, Vikram Kodibagkar, Yang Kuang, Mark Preul

This study assesses the feasibility of estimating and quantifying the uncertainty in growth parameters for a mathematical model of glioma growth from MR imaging.  Five immunocompetent albino mice were inoculated intracranially with syngeneic GL261 tumor cells and followed by serial imaging for 25 days.  We simulated the growth of the tumor from the known initial conditions using a popular two-parameter reaction-diffusion model and compared the results with the imaging.  Our simulations show that the growth and diffusion rates in the model cannot be identified from imaging data alone.  Uncertainty quantification in model predictions of the tumor is problematic.

Chen Niu, Xiao Ling, Pan Lin, Kun Zhang, Xin Liu, Hao Song, Liping Guo, Wenfei Li, Maode Wang, Ming Zhang

The aim of this study is to evaluate whether the lesion in frontal lobe would cause the change of brain positive and negative network interaction, thereby affecting cognitive function. We employed a MSIT to compare the task-positive and DMN changes of brain tumor patients and the healthy controls. Our results indicated the interaction relationship between the task-positive and DMN in patients with brain tumor in the frontal lobe was significantly decreased. We suggest that reduced anti-correlation between DMN and task-positive networks in patients with brain tumor may be caused by dysfunctional DMN, thus affecting the cognitive function of patient.

Xiao Ling, Chen Niu, Pan Lin, Kun Zhang, Xin Liu, Wenfei Li, Liping Guo, Ming Zhang*

The aim of the study was to observe the activation of DMN in patients with different types and location brain tumors, and as so to investigate whether the type and location of tumor would affect DMN spatial distribution. In our study, we compared the spatial distribution of DMN both glioma and meningioma. Finally, our findings show that DMN integrity is impaired as a result of tumor, and the DMN spatial distribution could be affected by the location of the brain tumor. 

Zhongxu An, Vivek Tiwari, Sandeep Ganji, Marco Pinho, Bruce Mickey, Edward Pan, Elizabeth Maher, Changho Choi

We present a 3D high resolution 2HG and other metoblites imaging in gliomas with metoblic correlation mapping technique to differentiate areas with different metabolic activities.

Shan Wang, Jiangfen Wu

Texture analysis of DWI based on different ROI can provide various significant parameters to evaluate tumor heterogeneity, which were correlated with tumor grade. Particularly, the inhomogeneity value derived from whole tumor ROI provided high diagnostic value in differentiating HGGs from LGGs and predicting the status of tumor proliferation.

Yan Li, Stojan Maleschlijski, Sarah Nelson

The study evaluated the reproducibility of metabolite profiles within the normal appearing white matter that were acquired using automatic prescription of short echo time magnetic resonance spectroscopic imaging for ten patients with high grade glioma. 

Yingqiu Liuyang, Jin Shang, Yanwei Miao, Bing Wu, Yan Guo

In this study, the differential diagnostic value of histogram analysis of ADC signal value based on entire region of grade II and III tumor is investigated, and further aimed at revealing the microscopic changes of glioma in the evolution of low grade to high grade.Conclusion that,histogram analysis of ADC signal value based on entire tumor could provide more information in differentiation of grade II and III glioma. Several parameter showed superior diagnostic value. 

Jian Wang, Ling Wu, Juan Ma, Chunhui Jiang, Sailike Duishanbai, Geng Dangmurenjiapu, Chen Liu

Synopsis:This study aims to probe the role of the quantitative analysis of MR diffusion-weighted imaging in differentiating Cerebral Alveolar Echinococcosis (CAE) with Brain metastases (BM).There was significant difference of the mean ADC values and eADC values (P<0.05) of the solid region between CAE and BM. There was no significant difference of the mean ADC values (P>0.05) between CAE and BM,but there was significant difference that of the eADC values (P<0.05). MR-DWI was valuable for making diagnosis and differential diagnosis of patients with CAE and BM. EADC values is better than the ADC values. 

Frank Riemer, Mary McLean, Fulvio Zaccagna, James Grist, Rolf Schulte, Joshua Kaggie, Colin Watts, Stephen Price, Martin Graves, Ferdia Gallagher

Incomplete fluid suppression on fluid-attenuated inversion-recovery ²³Na-MRI (IR-²³Na-MRI) was observed in three patients undergoing IR-²³Na-MRI after gadolinium contrast injection, as part of a brain tumour imaging study. To evaluate this, ²³Na-MRI T₁ maps were acquired before and after injection of a gadolinium-based contrast agent on a grade IV glioma (GBM) patient, which showed a statistically significant change of ²³Na-MRI T₁ within the peritumoral oedema (p=0.0095). Gadolinium contrast-enhanced ²³Na-MRI could potentially add further applications for sodium imaging and probe tumour tissue structure in new ways to investigate proliferation and treatment response.

Hitomi Nagano, Koji Sakai, Jun Tazoe, Masashi Yasuike, Hajime Yokota, Kentaro Akazawa, Naoya Hashimoto, Kei Yamada

Q-space imaging (QSI) is an extended version of diffusion weighted image technique which can be utilized for observing microstructure of brain in micrometer order. In order to assess whether QSI can differentiate between the two most common extra-axial brain tumors of the posterior fossa, we performed histogram analyses as well as ROC analyses on the q-space data of meningioma and cranial nerve schwannoma (CNSch). We also assessed the apparent diffusion coefficient (ADC) for comparison. As a result, we have shown that mean displacement derived from QSI as well as ADC are able to differentiate meningioma from CNSch.

Shanshan Jiang, Charles Eberhart, Maria Adelita Villalobos, Xianlong Wang, Yu Wang, Hao Yu, Tianyu Zou, Yongxing Du, Hye-Young Heo, Yi Zhang, Peter Zijl, Jinyuan Zhou, Zhibo Wen

We explored the radiographic features of isocitrate dehydrogenase (IDH) wildtype and mutated tumors in glioma patients preoperatively using APTW imaging at 3 Tesla. 26 patients with newly suspected low-grade gliomas were recruited, surgical specimens were obtained for pathological analysis, and corresponding APTW signal intensities were recorded. Results showed that the IDH1 wild-type tumors had significantly higher APTW signal intensity than the IDH1 mutant tumors. The area under the ROC curve (AUC) for APTW to differentiate IDH1 wild-type from IDH1 mutant was 0.750. APT imaging has the potential for discriminating IDH genotypes in WHO grade-II gliomas.

Dennis Hedderich, Anne Kluge, Thomas Pyka, Claus Zimmer, Jan Kirschke, Benedikt Wiestler, Christine Preibisch

Aim of this study was to investigate the influence of leakage correction methods on dynamic susceptibility contrast (DSC)-based measures of cerebral blood volume (CBV), using patient data acquired with and without pre-bolus. Two post-processing techniques were compared with respect to normalized CBV (nCBV) in contrast enhancing tumor tissue. Generally, CBV increased or decreased after leakage correction for data acquired without or with prebolus, respectively. The best agreement between corrected nCBV values, obtained in the same patients without and with prebolus, respectively, was obtained for a reference curve-based correction approach.

Farida Grinberg, Ganna Blazhenets, Francesco D’Amore, Ezequiel Farrher, Christian Filß, Karl-Josef Langen, N. Jon Shah

PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) provides important diagnostic information in brain tumours. In this work, we report a novel combined application of PET imaging and MRI with advanced non-Gaussian diffusion MRI methods including diffusion kurtosis imaging and gamma-distribution function imaging. This is the first multimodal study combining metabolic information from FET-PET and microstructural information gained from non-Gaussian diffusion models. The main goal was to investigate the advantages of such a combined application in tumour assessment and to compare the sensitivity of various non-Gaussian diffusion metrics to the underlying microstructural tissue properties. 

Melanie Morrison, Andrew Leynes, Angela Jakary, Prasanna Parvathaneni, Peder Larson, Janine Lupo

In the treatment of gliomas, radiation therapy (RT) is associated with long-term effects including vascular injury in the form of cerebral microbleeds (CMBs), and changes in the white matter and thickness of cortex. Ultra high-field MRI techniques were used to characterize RT-induced changes across serial scans in support of ongoing investigations of the role of anti-angiogenic therapies in minimizing treatment effects. Steady increases in the number of CMBs was observed decades post-RT. CMB foci were characterized by increased isotropic diffusion when compared to surrounding white matter, which showed signs of degradation in as few as two months between serial scans. 

Akira Kunimatsu, Kouhei Kamiya, Yasushi Watanabe, Yuichi Suzuki, Natsuko Kunimatsu, Harushi Mori, Osamu Abe

We evaluated the feasibility of machine learning-based differentiation between glioblastoma and primary central nervous system lymphoma by using texture features of post-contrast MR images. Cross validation showed that more than 80% of teacher data were correctly assigned. Trial data comprised of atypical image variants were correctly assigned in up to 78.6% by the best classifiers.

Jason Johnson, Mu-Lan Jen, David Shin, Ping Hou, Caroline Chung, Donald Schomer, Ho-Ling Liu

CBF quantification using ASL is an important MR technique for the evaluation of suspicious enhancing lesions for patients’ status post chemotherapy treatment. The quantification requires an estimate of equilibrium magnetization of blood which is often obtained using a set of proton density (PD) reference images; however, this approach can lead to errors in CBF based on tissue variation in PD which could then lead to inaccurate assessment of pseudo-progression (PsP) versus true progression (TP). Our work showed that PD variation led to a reduced diagnostic performance of CBF particularly in the region of enhancing lesions with pathologic proven TP.

Ai-Ling Hsu, Ping Hou, Sujit Prabhu, Rivka Colen, Ashok Kumar, Jason Johnson, Donald Schomer, Jyh-Horng Chen, Ho-Ling Liu

Resting-state fMRI has been shown its potential for pre-surgical mapping. The potential confounds are commonly removed by regressing out the averaged fluctuation over masks of white matter and cerebrospinal fluid. However, for the patients with brain lesions, these masks may be contaminated by lesions. In current study, we generated masks by segmentation and template approaches. Although these masks were contaminated by lesion in most of our patients, no significant difference in FC was found due to this effect, which might be related to small samples. Comparing to segmentation approach, more variable results were observed when masks obtained by template approach. 

Miaomiao Wang, Rihua Jiao, Yanan Li, Congcong Liu, Jianxin Guo, Chao Jin, Jian Yang

In this study, a new approach for assessing distribution of bloodstream  inflow and outflow type based on the three-time point (3TP) method was used to semi-quantitative analysis of the microcirculation characteristics in whole pituitary adenoma by dynamic contrast-enhanced MRI (DCE-MRI). The volume percentage of persistently enhancing type of time-intensity curve (TIC) in adenoma was higher than normal region. Meanwhile, adenomas with hyperprolactinemia were shown a significant decrease of volume percentage in speed up the downhill type when compared with the adenoma without hyperprolactinemia. This method could identify the different distribution of vascularity between normal pituitary and subtype of adenoma.

Chunhui Jiang, Jian Wang, Juan Ma, Abudureheman Yibanu, Chen Liu

Objective  To evaluate the role of the ADC value in patients with high-grade glioma (WHO III-IV) using high B-value diffusion weighted imaging (DWI), as a potential noninvasive quantitative index in defining the boundary of glioma. Methods  25 cases of surgical pathologically confirmed glioma underwent the DWI scan with b=1000 and 3000s/mm² respectively in a 3T MR scanner. The ADC values of the glioma substantial zone, cerebral parenchyma within 0-10/10-20mm radium and the cerebral parenchyma of the opposite sphere are statistically analyzed by SPSS17.0. Results When b=1000 and 3000 s/mm², the difference in the ADC values of the tumor and the 0-10mm region had no statistical significance(P>0.05). When b-value = 1000 s/mm², there is statistically valid difference among ADC values of 10-20mm area, lesions and comparing group (P<0.05); When b-value =3000 s/mm², there is no statistically valid difference among ADC values of 10-20mm area and lesions(P>0.05). The ADC value of 10-20mm area is validly lower than the lesions. Conclusion  The ADC value in high B value DWI scan indicating that the ADC value is more sensitive in quantitatively analyzing the infiltration zone of glioma relative to the low B value DWI scan.

Hong Guo

Applying vessel size imaging(VSI) and dynamic susceptibility contrast MR (DSC-MR) to explore difference of the microvessel between grade ? and ? oligodendroglioma. We discovered both VSI and DSC-MR could identify different grades of oligodendroglioma, but the power of VSI was better than DSC-MR.

Morteza Esmaeili, Anne Line Stensjøen, Erik Berntsen, Ole Solheim, Ingerid Reinertsen

In this study we assess the growth pattern of one of the most aggressive brain tumor in adults. Surgery is a standard of care for these patients, and understanding the prominent growth direction of tumor lesions can eventually benefit surgical planning. Contrast-enhanced MR data at two time-points of diagnosis and pre-operation were analyzed to derive mean 3D vector field demonstrating the growth directions. A DTI white matter (WM) atlas was used to investigate the degree of agreement and alignment of the generated vector field towards white matter fibers.

Sumei Wang, SANJEEV CHAWLA, Mohamed Metkees, Seyed Nabavizadeh, Gaurav Verma, Arastoo Vossough, Suyash Mohan, Harish Poptani

To determine whether combined use of diffusion and perfusion MRI can help in differentiating brain infections from glioblastomas (GBMs), 13 patients with infections and 20 patients with GBMs underwent DTI and DSC-PWI. Significantly lower median values of mean diffusivity (MD) and higher fractional anisotropy (FA) were observed in central core of infective lesions than in GBMs. Additionally, significantly decreased median and maximum values of relative cerebral blood volume (rCBV) from enhancing region were observed in patients with infections compared with those of GBMs.  The best classification model consisted of MD from central core and rCBV_max from enhancing region. 

Zhe Liu, Xiang Li, Ting Liang, Tong Bian, Miao Wang, Li Sun, Gang Niu, Jian Yang

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been provided for noninvasive assessment of different grade of gliomas. But the diagnostic performance of this new approach was variant among the recent reports. This study included 10 DCE-MRI studies regarding to differentiating high grade gliomas (HGGs) from low grade gliomas (LGGs). The meta-analysis results demonstrated that parameters of DCE-MRI have high diagnostic performanc (Ktrans and Ve) in distinguishing HGGs from LGGs. DCE-MRI can be used as an important tool for the assessment of neovascular permeability and for the pre-operative grading of glioma.

Yae Won Park, Sung Soo Ahn, Seung-Koo Lee

Preoperative prediction of genotypic classification with MRI is useful because IDH mutation and 1p/19q codeletion status are important prognostic and predictive factors in lower-grade gliomas (WHO grade II and III). In this study we found that various preoperative imaging features including lobar/nonlobar or central location, enhancement characteristics, tumor margin, diffusion characteristics, ependymal/cortical involvement were different between IDH-wildtype and IDH-mutant group. Therefore preoperative MRI may be helpful to predict IDH mutation status in lower-grade gliomas.

Xin Chen, Zaiyi Liu, Xinqing Jiang, Xinhua Wei, Zhongping Zhang

Glioblastoma multiforme (GBM) is the most frequent and deadly type of primary malignant tumor in the central nervous system with a median survival range of only 9-15 months. We developed and validated a MRI-based radiomics classifier to predict overall survival(OS) in patients with newly diagnosed GBM. The results showed that a 7-radiomics classifier allows prediction of survival and stratification of patients with newly diagnosed GBM into a low- or high-risk group for OS.

Charlotte Debus, Maximilian Knoll, Sebastian Adeberg, Stefan Rieken, Jürgen Debus, Amir Abdollahi

Tumor delineation in radiotherapy planning of high grade glioma is challenging due to infiltrative growth patterns and physiological tumor heterogeneity. We used random forest machine learning to classify tissue types and predict tumor progression based on parameters derived from multi-modal functional and metabolic imaging. In an integrative approach, eight patients with recurrent high grade glioma were investigated retrospectively, and the resulting predicted tumor volumes were compared to standard T₁ weighted contrast-enhanced MRI based segmentations. Predictions of tumor tissue could identify original tumor volumes well and yielded promising results with respect to tumor progression in terms of sensitivity and specificity.

Hong Zhang, Yi Zhang, Xiaolu Tang, Huiying Kang, Di Hu, Jinyuan Zhou, Yun Peng

Amide proton transfer (APT)-MRI is a chemical exchange saturation transfer (CEST) based approach in which the amide protons of endogenous proteins and peptides are irradiated to accomplish detection using the water signal. In this study, the APT approach was incorporated with standard brain MRI sequences and applied to children with cerebellar tumors at 3T. The initial results show that APT imaging can enhance the noninvasive identification of tissue heterogeneity and may be a biomarker of tumor grade in pediatric cerebellar tumors.

Ka-Loh Li, Ibrahim Djoukhadar, Sha Zhao, Natale Quartuccio, Amy Watkins, Xiaoping Zhu, Alan Jackson

The relationship between three functional parameters related to cell density, ADC, R1_N, and v_e, were examined in 12 patients with vestibular schwannomas pre- and post- anti-angiogenic therapy.  3D maps of R1_N obtained with variable flip angle images, and v_e derived from DCE-MRI were compared to 3D maps of ADC. The tumor mean values of ADC, R1_N and v_e showed correlation to each other before bevacizumab treatment. This correlation was lost after three-months of treatment. Both R1_N and ADC displayed power in prediction of treatment.  R1_N showed more sensitive to anti-angiogenic therapy induced changes in VS than ADC or ve.

Ovidiu Andronesi, Morteza Esmaeili, Ronald Borra, Kyrre Emblem, Elizabeth Gerstner, Marco Pinho, Scott Plotkin, Andrew Chi, April Eichler, Jorg Dietrich, Percy Ivy, Patrick Wen, Dan Duda, Rakesh Jain, Bruce Rosen, Gregory Sorensen, Tracy Batchelor

Precise assessment of treatment response in glioblastoma during combined antiangiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes probed by MRSI are more specific for tumor physiology and less confounded by changes in blood-brain barrier permeability.

Jing Zhao, Yiying Zhao, Yinsheng Chen, Zhongping Chen, Yin Wu

Amide proton transfer (APT) MR imaging has proved to be capable of detecting/grading brain tumors as well as assessing treatment response. Routinely used magnetization transfer (MT) asymmetry is contaminated with MT, nuclear overhauser effect (NOE) and T₁ relaxation time of water. In this study, the dominant contributors of direct water saturation and MT to Z-spectrum were estimated from a sum of two Lorentzian functions, and APT was corrected with T₁ scale and inverse Z-spectrum analysis. Results showed that the corrected APT can reliably depict glioma heterogeneity post-treatment, in accordance with H & E histological observations.

Marco Pagani, Joanna Pucilowska, Camilla Robol, Joseph Vithayathil, Caitlin Kelly, Colleen Karlo, Riccardo Brambilla, Gary Landreth, Alessandro Gozzi

16p11.2 microdeletion is the most common copy number variation in autism. Recent studies revealed that mice harboring this microdeletion exhibit a paradoxical elevation of ERK activity, macroscale gray matter abnormalities and autistic-like behavioral deficits. By using high-resolution morpho-anatomical MRI, we show that prenatal treatment with an ERK pathway inhibitor rescues hippocampal and septal anatomical deficits in 16p11.2del mutants. The effect was associated with amelioration of anxiety behaviors. These results provide the first example of the rescue of developmental gray matter abnormalities in this mouse model, and support the translational use of structural MRI to assess putative therapeutic effects in autism.

Horea-Ioan Ioanas, Bechara Saab, Markus Rudin

The serotonergic system is a high-centrality node in the brain network implicated in affective disorders and their treatment. We use optogenetics, fMRI, and pharmacology to image serotonergic effects of antidepressant treatment in mice at the whole-brain level. We stimulate the ascending serotonergic system and perform functional imaging at multiple time points over the course of antidepressant (fluoxetine) treatment. We establish the feasibility of this paradigm, and report two trends in serotonergic kinetics: (a) increased serotonergic system signal transmission upon acute, but not chronic fluoxetine administration, (b) decreased serotonergic system excitability during the first phase of chronic fluoxetine administration.

Kurtis Stewart, Owen O'Daly, Gareth Barker, Katrina McMullen, Veena Kumari, Steven Williams, Gemma Modinos

We applied graph theoretical network analysis on multi-echo resting-state fMRI data to examine whether healthy people with subclinical psychotic-like experiences (schizotypy) show abnormal functional brain topology compared to similar subjects without such experiences. While we did not observe significant between-group differences in any connectivity measure (Local and global efficiency, Modularity, and Small-worldness), within the schizotypy group we found that modularity and small-worldness were directly related to the severity of subclinical psychotic-like experiences. This demonstrates the feasibility of applying graph theory on multi-echo rs-fMRI in individuals with vulnerability for psychotic disorders and encourages the application of these methods in psychosis research.

Ying Liu, Huishu Yuan, Xiangzhu Zeng, Zheng Wang, Lizhi Xie

The aim of this study is to explore the potential differences of the quantitative CBF values among patients with depression, patients with hypertension and patients with comorbid hypertension in depression by using whole brain 3D PCASL and to investigate the correlation between CBF values and degrees of depression. The results indicate that CBF values decrease in frontal and parietal lobes in patients with comorbid hypertension in depression, whereas not in patients with depression or patients with hypertension, hypertension may play a synergistic action in the progress of depression.

Adam Liska, Ryszard Gomolka, Mara Sabbioni, Alberto Galbusera, Stefano Panzeri, Maria Luisa Scattoni, Alessandro Gozzi

Functional connectivity aberrancies as measured with resting-state fMRI (rsfMRI) have been consistently observed in the brains of autism spectrum disorders (ASD) patients. However, genetic and neurobiological underpinnings of these findings remain unclear. Here we used rsfMRI to show that homozygous mice lacking the strongly ASD-associated gene CNTNAP2 exhibit default-mode network connectivity alterations associated with reduced social investigation, a core “autism trait” in mice. These findings reveal a causal link between an ASD-associated mutation and functional connectivity aberrancies and suggest that homozygous loss-of-function mutations in CNTNAP2 may predispose to ASD through a selective dysregulation of functional coupling between integrative cortical areas.

Yan Li, Naying He, Hongmin Xu, Chencheng Zhang, Weibo Chen, Yansong Zhao, Yi Zhang, Jinyuan Zhou, Haiyan Jin, Fuhua Yan

The aim of this study is to evaluate the feasibility of amide proton transfer-weighted (APTW) MR imaging to detect cerebral abnormalities in patients with obsessive-compulsive disorder (OCD) and to explore its clinical utility. Five OCD patients and 9 normal healthy controls (NC) underwent APTW MR imaging. The magnetic resonance ratio asymmetry (MTR_asym) values at 3.5ppm of anterior cingulate cortex (ACC) and thalamus were measured on axial APTW images. We found a trend of increased MTR_asym(3.5ppm) or APTW within ACC in OCD patients compared with controls. No significant difference was found between groups in the MTR_asym(3.5ppm) within bilateral thalamus. Our results suggest that APTW imaging maybe a promising approach to investigate pathological changes underlying OCD and may provide insights into clinical diagnosis of OCD.

Marco Pagani, Alberto Galbusera, Alessandro Gozzi

Mice lacking CNTNAP2 exhibit robust autism-like behavioral traits, including stereotyped behaviors and excessive self-grooming. By using high resolution morpho-anatomical imaging in CNTNAP2 mutant mice, we identified marked volumetric alterations subcortical substrates implicated in ASD motor stereotypy, with a prominent involvement of the dorsal striatum. Importantly, we also show that in mutant mice, striatal but not cortical regions, exhibit dramatically expanded gray matter network extension, encompassing aberrant trophic interaction between limbic, subcortical and prefrontal regions. The observed striatal volumetric and gray matter network abnormalities serve as a plausible morpho-anatomical substrate for some of the stereotypy exhibited by CNTNAP2 mutant mice.

Marco Pagani, Camilla Robol, Richard Gomolka, Adam Liska, Alberto Galbusera, Anna Aksiuto, Alessandro Gozzi

Mutations in autism-associated gene Shank3 have been associated to alterations in striatal function and core autistic behaviors. However, the neocortical substrates affected by Shank3 mutations remain undetermined. By using structural and functional MRI in Shank3B mutant mice, we identified key alterations in prefrontal and associative regions of the mouse default mode network (DMN). Specifically, we show that prefrontal and antero-posterior areas of the DMN present decreased gray matter volume, an effect associated with reduced local and long-range prefrontal functional connectivity. Our findings suggest that Shank3 mutations may predispose to autism via a selective trophic and functional downregulation of prefrontal areas.

Wenjing Zhang, Wade Weber, Huaiqiang Sun, Min Wu, Qiyong Gong, Melissa DelBello, Su Lui

With an objective neuroimaging data-driven method using agglomerative hierarchical clustering analysis, two patterns of cortical matter changes among 58 first episode bipolar manic adolescents has been identified. And the clinical feature especially the intelligence quotient was corresponding to the subtyping among these patients. While the effect of medication and illness duration have been minimized, our findings provided new evidence indicating the existence of two neurobiologically distinct subgroups of patients with first episode bipolar mania, which may reflect qualitatively distinct genetic influences or neurodevelopmental alterations.

Carola Canella, Adam Liska, Valentina Piretti, Alberto Galbusera, Adam Schwarz, Alessandro Gozzi

NMDA receptor antagonists like ketamine or phencyclidine (PCP) induce robust schizophrenia-like symptoms in rodents via glutamatergic disinhibition of cortico-limbo-thalamic substrates. We show that acute administration of PCP in the mouse elicits aberrant fronto-hippocampal and thalamo-cortical functional connectivity, an effect that can be prevented by pharmacological activation of M1/M4 muscarinic receptors. These changes highlight a previously unreported permissive contribution of muscarinic receptors on the aberrant connectional signatures produced by NMDAr antagonism which bear relevance for human connectivity mapping in hyperglutamatergic states and schizophrenia. 

Hsin-Yu Chen, Chia-Min Chen, Teng-Yi Huang, Tzu-Chao Chuang

In this study, we attempt to use machine-learning algorithms for ADHD classification with cerebral cortical thickness. We compared three cortical parcellation schemes and three different sets of features. The results supported the usage of Aparc and A2009s of FreeSurfer and suggested that recursive feature elimination effectively increased the predication accuracies. In addition, gender is an influential feature for the classification.

Muriel Bruchhage, Ilse van Ooijen–van de Vondervoort, Erwin Blezer, Katarzyna Kapusta, Houshang Amiri, David Lythgoe, Marcel Zwiers, Rick Dijkhuizen, Jeffrey Glennon, Sarah Durston, Daniel Brandeis, Jan Buitelaar, Steven Williams, Flavio Dell'Acqua

Obsessive-compulsive disorder (OCD) and diabetes mellitus type 2 (DM2) show compulsive behaviour1 and share genetic vulnerability2. Using Diffusion Tensor Imaging as a translational approach, we investigated differences in corpus callosum (CC) body white matter microstructure in a paediatric human OCD cohort and juvenile animal models for OCD and DM2. In all three groups, fractional anisotropy increased in the CC body compared to controls, which correlated with increasing compulsive behaviour. This was coupled with a decrease in CC mean diffusivity in the animal models. Our results underline the importance of compulsive behaviour as a possible trans-diagnostic trait across OCD and DM2.

Jing-Ying Huang, Chih-Min Liu, Tzung-Jeng Hwang, Yu-Jen Chen, Yung-Chin Hsu, Hai-Gwo Hwu, Wen-Yih Tseng

To investigate the relations between white matter tracts and treatment outcome, we performed diffusion spectrum imaging (DSI) and whole brain tract-based automatic analysis (TBAA) comparisons of the tract integrity over the whole brain. As compared with health controls, non-remitted patients showed reduced integrity in 7 fiber tract bundles, whereas remitted patients only showed 4 fiber tract bundles. When comparing with remitted patients, non-remitted patients showed reduced integrity in the same 7 fiber tract bundles as those found in comparison with healthy controls. Our results support that remitted and non-remitted patients had distinctly different severity of tract alterations.

Zhujing Shen, Peiyu Huang, Chao Wang, Wei Qian, Minming Zhang

To investigate the role of amygdala in nicotine dependence, we examined its structural and functional changes in smokers. Volume, amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) was used to detect differences. Results showed that although there was no significant volume change, right amygdala activity increased in smokers compared with nonsmokers. Furthermore, FC between the left amygdale and left orbit frontal cortex (OFC) increased while the right amygdale and bilateral OFC decreased in smokers. These results suggest that abnormal amygdala function may underlie the occurrence of nicotine dependence.

Linghui Meng, Kaiming Li, Jing Jiang

    To reveal how traumatic events affect the integrity of brain microstructure in trauma-exposed non-PTSD people, we performed a longitudinal tract-based spatial statistics (TBSS) analysis in earthquake survivors using diffusion tensor imaging (DTI) data collected 25 days (TimePoint 1) and 2 years (TimePoint 2) after the Wenchuan earthquake. Our results showed that fractional anisotropy (FA) in several brain regions at TimePoint 2 were significantly increased compared with those at TimePoint 1. The increased FA in these regions may serve as the underlying neural substrates as brain recovered from the trauma.

Huawei Zhang, Xiaoqi Huang, Zhiyun Jia

Suicide is a serious public health problem, but little is known of microstructural abnormalities of white matter regarding suicidal ideation (SI). Sixteen depressive patients with SI, 16 depressive patients without SI and 32 age- and gender-matched healthy controls received MRI scans on a 3T magnet. Whole-brain voxel-based analysis was used to compare fractional anisotropy (FA) across the three groups with threshold at p<0.005(uncorrected) at voxel level and 50 for cluster size with SPM8. The three groups had significant differences of FA in the left centrum semiovale (peak Z=4.64 at -30, -38, 34), right centrum semiovale (peak Z=3.54 at 32, -34, 32) and right splenium of corpus callosum (peak Z=4.64 at 4, -34, 12). The alterations of white matter tract indicate that white matter integrity, especially a “frontal-related WM disconnection” may underlie the pathophysiology of suicidal ideation in depression.

Jing-Ying Huang, Chih-Min Liu, Tzung-Jeng Hwang, Yu-Jen Chen, Yung-Chin Hsu, Hai-Gwo Hwu, Wen-Yih Tseng

 To investigate whether remitted and non-remitted patients with schizophrenia had distinctly different gray matter volumes, we used voxel-based morphometry (VBM) to analyze group difference by controlling all possible clinical variables. As compared with remitted patients, the non-remitted patients showed 10 brain areas with significantly decreased gray matter volume. Our results imply that remitted and non-remitted patients might have distinct patterns of gray matter reduction, and the characteristics of gray matter change might represent the structural correlate of treatment response in patients with schizophrenia.

Dong-Hoon Lee, Do-Wan Lee, Ji-Yeon Park, Hae-Jin Park, Kyu-Ho Song, Yong Hyun Chung, Dong-Cheol Woo, Bo-Young Choe

Alcohol is the most commonly abused intoxicating substance among young and middle-aged adults, and ranks highly as a cause of disability and mortality. A pattern of heavy consumption, called binge drinking, leads to various psychiatric disorders. We used in vivo proton magnetic resonance spectroscopy (¹H MRS) to quantitatively assess neurochemical responses in hippocampus in a rat model of repeated-binge alcohol (RBA) intoxication. We determined that choline-containing compound, gamma-aminobutyric acid, and total N-acetyl-aspartate (tNAA: N-acetyl-aspartate + N-acetyl-aspartyl-glutamate) signals were highly sensitive to binge alcohol intoxication, which provides insights into neurochemical alterations associated with alcohol abuse.

Chuan Huang, Karl Spuhler, Mala Ananth, Elizabeth Bartlett, Jie Ding, Xiang He, Christine DeLorenzo, Ramin Parsey

Bipolar disorder is one of the most prevalent psychiatric diseases in developed countries, and virtually all major psychiatric associations recommend lithium as the first line therapy for bipolar patients in the depressive phase of the illness, despite relatively low response rate for the drug and relatively high likelihood of side effects. However, no predictive criteria which indicate an individual patient’s responsiveness to lithium are employed clinically. In this work, we present preliminary findings demonstrating an association between baseline, multimodal neuroimaging measurements and lithium treatment outcome. 

qiaoling zeng, xiaojun guan, min xuan, quanquan gu, xiaojun xu, minming zhang

Studied longitudinally 21 PD patients using Eigenvector centrality mapping,discovered significantly decreased  EC values in right postcentral gyrus, and increased EC values in right cerebellum, right supplementary motor area (right SMA) as compared to B group. right postcentral gyrus in F group is negativelycorrelatedwithhoehn and yahr staging( HY) stage (r =-0.48, p < 0.05). Variation of EC values (F group-B group) in right cerebellum is positively correlated with changeofUPDRS-III scores. The current study demonstrated that deterioration and compensation exists through different circuit along with PD progression.

Icaro Oliveira, Tiago Guimaraes, Roberto Souza, Antonio Santos, Jaime Hallak, Renata Leoni

Schizophrenia is a mental disorder with structural and functional alterations that are not completely comprehended. We used a pseudo-continuous ASL protocol to investigate changes in resting CBF in schizophrenic patients. In addition, quantitative T1 and Gray Matter Volume (GMV) were assessed. Decreased CBF, GMV, and T1 values were observed in schizophrenic patients compared with healthy controls in several brain regions consistent with patients’ symptoms, such as deficits in planning solving and organizing thoughts. Therefore, motor, sensorial and cognitive impairments observed in schizophrenia may be related to CBF deficits and structural alterations in localized brain regions.

Rajesh Kana, Haley Bednarz, D Rangaprakash, Gopikrishna Deshpande

Autism spectrum disorders (ASD) are neurodevelopmental disorders that have been associated with disruptions in brain connectivity. Using resting-state fMRI, we assessed the variability of whole-brain connectivity in individuals with ASD. Using a variable, sliding-window technique to calculate the variance of dynamic functional connectivity (vDFC), we show increased vDFC in ASD as compared to typically developing controls among prefrontal regions and within the salience network. Measures of vDFC were significantly correlated with measures of social functioning among all subjects. This work is significant as it suggests increased neural noise and disorganization in ASD.

Lu Lu, Lianqing Zhang, Xuan Bu, Hailong Li, Xiaoxiao Hu, Ying Chen, Xinyu Hu, Lanting Guo, Qiyong Gong , Xiaoqi Huang

The current study combine the analysis of the cortical measures and subcortical structures’ volume to evaluate the cerebral structure alterations in a relative large drug-naive ADHD sample. In addition, we also invest the anatomical–age correlation between two groups. Our findings (i) highlighted the crucial role of the frontostriatal circuits in the pathophysiology of ADHD, (ii) indicated the abnormality in neural development trajectory in ADHD.

Chuan Huang, Karl Spuhler, Christine DeLorenzo, Ramin Parsey

Major Depressive Disorder is a debilitating illness that impacts 1 in 6 people in the United States during their lifetime. Particularly when monoamine levels are low, depression is associated with reduced volume in the front-limbic-striatum emotional processing network. Catechol-O-Methyltransferase (COMT) is responsible for most dopamine degradation in the frontal cortex. Guided by past literature, we examined the effect of COMT genotype on white matter integrity in the amygdala, hippocampus and parahippocampus in depressed patients along with healthy controls. Our results suggest the existence of sex-genotype interaction which is clinically relevant for women suffering from depression.

Qiang Luo, Ziqi Chen, Xinyu Hu, Xiaoqi Huang, Qiyong Gong

We used the SDM software to detect the similarities and differences of gray matter (GM) volume between MDD and BD, and found the significant decreases of GM in the bilateral insula and left inferior frontal gyrus (LIFG) characterized both MDD and BD-I, which  may be related with the clinical symptoms including using few words and exhibiting poor choices of conversation topics during depressive state in both two affective disorders. AND the MDD patients had significantly lower GM volumes in the right superior temporal gyrus and right amygdala in comparison with BD-I patients, which indicated that reduced GM volume in the right angular gyrus specifically characterizes BD-I which may contribute to the manic symptom.

Stijn Michielse, Jim Os, Machteld Marcelis

N/A

Jeffrey Berman, J Edgar, Lisa Blaskey, Emily Kuschner, Timothy Roberts

Alterations to the auditory system’s structure and function may underlie the auditory processing and language disorders prevalent in autism spectrum disorder (ASD).  This multimodal study compared DTI of the brainstem auditory pathway to magnetoencephalography (MEG) measures of auditory conduction velocity (M100 latency).  The M100 latency measures the time between auditory stimulus and auditory cortex response. DTI and MEG were acquired from 29 children with ASD and 31 controls. Increased brainstem auditory pathway FA was predictive of faster signal conduction in controls (shorter M100 latency) (p<0.01), but not ASD. These results indicate ASD impacts the structure-function relationships throughout the auditory system.  

Tao Li, ming zhao

By using the VBM method,We found Neuronal damage may occurred in the early stage of the PTSD patients and dysfunction in orbitofrontal cortex, insula cortex which involving in the limbic system, and the precuneus involving in the DMN might play a critical role in pathophysiology of PTSD. By using the SPS rat model to mimic the PTSD disease, we also found iron accumulation in the prefrontal cortex, striatum, hippocampus in the SPS rat model. This study indicated that iron may be involved in the pathology of PTSD, and could be nominated as a novel molecule involved in the pathology of PTSD and provide a potential target for therapeutic intervention of PTSD.

Kaundinya Gopinath, Binod Thapa-Chetry, Lou Ouyang, Lisa Krishnamurthy, Venkatagiri Krishnamurthy, Aman Goyal, Parina Gandhi, Yan Fang, Unal Sakoglu, Robert Haley

Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW illness (GWI), which is characterized by multiple deficits in cognitive, emotion, somatosensory and pain domains. In this study we examined 22 GWI patients and 30 age-matched controls with resting state fMRI (rsFMRI) in order to map impairments in brain function networks in GWI with graph theory based advanced network analysis methods. Results show widespread impairments in functional connectivity of cognition, affective, somatosensory and pain processing brain function networks in GWI consistent with multi-symptom nature of the illness.

Baohong Wen, Dandan Zheng, Ge Yang, Tianyong Xu, Jingliang Cheng

Myopia is a major cause of blindness worldwide. 134 patients with high myopia and 120 emmetropic volunteers were examined. All of the participants were scanned by high resolution 3D T2-weighted CUBE MRI sequence. This study is to evaluate the preoperative localization and postoperative assessment value of high-resolution 3D MRI for high myopia. It is shown that the axial length, horizontal length, vertical length and volume of the high myopia were significantly longer than those of the emmetropia. And high resolution 3D MRI could clearly demonstrate the position of staphylomas, superior rectus, inferior rectus, medial rectus, lateral rectus and optic nerve.

Baohong Wen, Ge Yang, Dandan Zheng, Tianyong Xu, Jingliang Cheng

Eyes of 66 high myopia patients who were to undergo posterior scleral reinforcement surgery (PSR) were examined by high-resolution three dimension cube magnetic resonance imaging. It is demonstrated that 3D MRI technique is helpful to PSR preoperative localization by comparing the precision rate of buckling strips position in groups with and without 3D MRI-guided. The present study demonstrates that it is possible to not only check the eyeball shape of the pathologic myopia patients accurately, but also assistant the PSR surgery by using 3D MRI technique.  

Peter de Blank, Michael Fisher, Marisa Prelack, Amy Waldman, Jeffrey Berman

DTI measures in the optic radiations are a promising biomarker of vision in children with optic pathway gliomas, but normal values for fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) in young children have not been defined.  In 40 children with neurofibromatosis type I (NF1) and 55 healthy control children between 0-14 years of age, we measured FA, RD and MD in the optic radiations. This study represents the first investigation of normal DTI measures in the optic radiations in young children and demonstrates an altered developmental trajectory in the optic radiations of children with NF1.  

Xiao-Quan Xu, Fei-Yun Wu

We applied multi-parametric magnetic resonance (MR) imaging techniques, including conventional MR, diffusion weighted imaging (DWI) and dynamic contrast enhance MR imaging (DCE-MRI) in the evaluation of orbital lymphoproliferative disorders (OLPDs).These three imaging techniques evaluated the morphologic, diffusion and perfusion characteristic,respectively. We aim to determine the optimal combination of parameters derived from 3T multi-parametric MR imaging for differentiating malignant from benign OLPDs.

Saikat Sengupta, Alex Smith, Samantha By, Ha-Kyu Jeong, Seth Smith

Optic Nerve DTI is of high interest in pathologies of the anterior visual pathway but high quality high-resolution diffusion MRI in the optic nerve is challenging because of involuntary eye motion. Vulnerability to motion induced phase errors is increased when multishot EPI (mshEPI) is used for achieving high imaging resolutions. In this abstract we present a triggered diffusion MRI approach with eye fixation that can significantly improve quality of optic nerve DTI, especially with mshEPI.

A Ankeeta, Senthil Kumaran, Rohit Saxena

Visual cortex is preserved and is performing during non-visual stimuli showing development of specific compensatory mechanisms associated with visual area in blind subjects. Blind people process auditory language stimuli faster than sighted people. Some language functions suggest cortical reorganization in the blind subjects.

A Ankeeta, Senthil Kumaran, Rohit Saxena

Tractography Based Spatial statistics was carried out on the DTI and T1 data acquired in 20 late blind, 20 early blind and 15 healthy controls at 3 T. Early blind showed more white matter impairments as compared to the late blind suggesting plasticity in the early blind than in the late blind. The cross modal plastic changes in the late blind were not as significant as those in the early blind subjects, supporting the conception of prospective plasticity of brain may decrease with onset of age of blindness.

Yanqiu Zhang, Dapeng Shi, Xirang Guo, Meiyun Wang, Xiaona Xu, Cuihua Zhao, Dandan Zheng

Possible effects on the structures of visual cortex using high-resolution anatomical MRI have not been established so far.  The aim of this study was to investigate volumetric alterations in visual cortex of RP patients using voxel based morphometry (VBM).  Our results demonstrated that RP is associated with degeneration of structures in the visual cortex, and prevention of visual cortical degeneration may need to become a new therapeutic goal for RP patients, which may have significant meaning for clinical to guide RP patients' treatment in a more reasonable way in future.

Chiara Maffei, Isabella Giachetti, Stefania Mattioni, Ceren Battal, Mohamed Rezk, Olivier Collignon, Jorge Jovicich

The human brain is capable of massive reorganization in case of sensory deprivation. Blind studies show white and gray matter changes depending on blindness onset. However, the anatomical reorganization of the optical tract in blind is largely unknown. We investigated the changes in the optic radiation tract using diffusion-based tractography techniques in early and late blind subjects compared to age- and gender-matched healthy sighted controls. We found activity-dependent alterations of the optical radiation, demonstrating the importance of visual experience for the integrity of the tract. The characterization of such reorganization processes may have clinical value when assessing sight restoration possibilities. 

Manzar Ashtari, Elena Nikonova, Kathleen Marshall, Gloria Young, Puya Aravand, Wei Pan, Gui-shuang Ying, Aimee Willett, Mani Mahmoudian, Albert Maguire, Jean Bennett

Leber’s congenital amaurosis (LCA) is a rare blinding disease with no cure. Recently, patients with LCA underwent retinal gene therapy and regained their vision to a great extent.  We followed this group of LCA patients before and up to three years on an annual basis after gene therapy using fMRI to assess the feasibility and durability of retinal gene therapy over time and the role fMRI could play as an outcome measure for other future retinal interventions.

Yongsheng Chen, Yang Song, Jiani Hu, Yongquan Ye, Yu Wang, Ying Wang, Bruce A. Berkowitz, Yan kang, Guang Yang, E. Mark Haacke

Imaging in vivo human retina remains a considerable challenge due to the thinness of the retina and eye motion.  Here we provide proof-of-concept data supporting the use of an asymmetric gradient echo scan with TE to 5 ms and an effective resolution of 37 μm in the readout direction after partial Fourier reconstruction. To reduce motion, we employed a cued-blinking strategy and collected the data multiple times and averaged data that after co-registration. Preliminary results showed retina/choroid layer clearly with sufficient SNR to obtain a transretinal T1 map from vitreous body to sclera.

Yolandi van der Merwe, John Gnalian, Ning-Jiun Jan, Ian Sigal, Kevin Chan

The structural organization and compositions of the corneoscleral shell determine the biomechanical behavior of the eye, and are important in aging and diseases such as glaucoma and myopia. However, characterizing the structure and composition of the eye and their changes with age or intraocular pressure remains a challenge. In this study, we showed that T2 mapping, magnetization transfer MRI and diffusion tensor MRI can be used to detect and differentiate age- and intraocular pressure-related changes in the porcine eyes. Multi-modal MRI may be useful for evaluating the biomechanical and (patho-)physiological mechanisms in the corneoscleral shell non-invasively and quantitatively.

Xiaoxiao Ma, Jinhao Lyu, Bing Wu, Jun Yang, Deihui Huang, Lin Ma, Xin Lou

The aim of our study was to characterize blood-brain barrier (BBB) permeability in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) using dynamic contrast-enhanced MRI (DCE-MRI). Twenty-two NMOSD patients and twenty-three MS patients were enrolled. Significantly higher BBB permeability were found in lesions and normal appearing grey matter in MS group when compared with NMOSD but no differences were observed in corpus callosum. Hence BBB permeability, measured by DCE-MRI may be used for differential diagnosis between NMOSD and MS and may provide novel insights into the underlying pathological differences.

Xiaoxiao Ma, Mengjie Fang, Jun Yang, Jinhao Lyu, Xin Li, Deihui Huang, Di Dong, Lin Ma, Xin Lou

The aim of our study was to ultilize combined radiomcis features extracted from T2-weighted MRI images as quantitative imaging biomarkers to differentiate neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Twenty-nine NMOSD patients and forty-five MS patients were enrolled. Our study showed 61 radiomics features and 8-feature-based radiomics signature were significantly different between NMOSD and MS. Therefore, radiomics may be an newly useful method which provides a promising non-invasive way of differentiating  NMOSD and MS.

Aimee Willett, Mani Mahmoudian , Gloria Young, Albert Maguire, Jean Bennett, Manzar Ashtari

Visual deprivation causes auditory-driven activity of occipital areas due to a process named auditory-visual cross modal plasticity. The present study explores the impact of visual restoration on this cross modal phenomenon and employs functional magnetic resonance imaging (fMRI) to describe changes in auditory task stimulation of the visual cortex after visual ability improvement in a population of eight Leber’s Congenital Amaurosis (LCA) patients. Results show the persistence of auditory-visual cross modal connectivity up to three years after gene therapy administration and reveal strong positive trends between visual ability after treatment and cross modal maintenance. 

Tsen-Hsuan (Abby) Lin, Willaim Spees, Michael Wallendorf, Yen-Yu Ian Shih, Anne Cross, Sheng-Kwei Song

Previously, we have successfully employed diffusion fMRI (dfMRI) to assess impaired axonal function in experimental autoimmune encephalomyelitis (EAE) mice undergoing visual stimulation. However, the prior dfMRI experiments cannot resolve contributions from retinal dysfunction to the decreased dfMRI changes observed in EAE mice. To address this shortcoming, we implanted an MR-compatible tungsten electrode at lateral geniculate nucleus (LGN) to perform antidromic stimulation of optic nerves. We demonstrated perpendicular apparent diffusion coefficient decreased with antidromic electrical stimulation at LGN bypassing visual input through retina.

Payam Nahavandi, Arun Niranjan, Yolanda Ohene, Ian Harrison, Ozama Ismail, Tracey Murray, Ross Johnson, Michael O'neill, Emily Collins, Jack Wells, Mark Lythgoe

There is a need for non-invasive biomarkers that enable accurate tracking of early, pre-symptomatic phases of Alzheimer’s disease (AD). Previous fMRI studies have differentiated AD patients from healthy controls. However, it is unknown whether the accumulation of tau or amyloid pathology is driving the fMRI irregularity. This is the first study to investigate whether tau pathology alone can modulate task-based BOLD fMRI. We observed stronger BOLD responses to visual stimulation in lateral geniculate nucleus and superior colliculus in the tau cohort, mirroring observations in mild AD and MCI patients. 

Zhipeng Yang, Jiliu Zhou, John Gore, Zhaohua Ding, Xi Wu

While fiber tractography using diffusion weighted MRI is a primary method that has achieved great success during the past decade, it however suffers from a number of inherent limitations. On the basis of the concept of a spatio-temporal correlation tensor we have introduced previously as a descriptor of the functional architecture in white matter, we propose in this study a novel algorithm for tractography by combing diffusion and functional MRI. Our experimental results show clear improvement of tractography accuracy for fiber tracts in the visual circuit, which demonstrates a great potential for reconstructing functional structure in brain whiter matter.

Han Yongliang, Li Yongmei, LUO Qi, ZENG Chun, WANG Jingjie, DU Silin, ZHANG Xiaohui, GUO Youyou

Neuromyelitis optica (NMO) is an inflammatory, demyelinating syndrome of the central nervous system characterized by severe attacks of optic neuritis and myelitis, but investigators in several studies observed abnormalities in deep gray matter. Functional MRI (fMRI) has the potential to further understanding of the neuropathologic mechanisms of NMO. In the present study, our aim was to investigate patients with NMO-related alterations of brain functional connectivity(FC) in resting state in default mode network (DMN) and frontoparietal network(FPN) using independent component analysis(ICA) and their correlations with clinical features.

Adnan Alahmadi, Rebecca Samson, Matteo Pardini, Egidio D'Angelo, Karl Friston, Ahmed Toosy, Claudia Gandini Wheeler-Kingshott

This study investigates the response to different grip force levels in the cerebellum and its dentate nucleus in MS. We found that cerebellar responses were functionally parcellated; with linear effects in the anterior cerebellum and complex nonlinear responses in the posterior cerebellum. This behaviour is consistent with healthy subjects (nonlinear responses in bilateral lobules V-VI and ipsilateral VIII), although MS subjects additionally show a strong linear response in lobule I-IV and nonlinear responses primarily localised in lobules V-VI. In the dentate nucleus, the motor portion in MS was silent as compared to the healthy subjects.

Sofia Dall'Orso, Johannes Steinweg, Alessandro Allievi , David Edwards, Etienne Burdet, Tomoki Arichi

The mature somatosensory cortex is known to be somatotopically organized, but it is not known when this functional organization emerges in human life. We aimed to map functional responses across  the somatosensory cortex of preterm infants using fMRI and automated robotic tools. A preterm “homunculus” topology was identified with a spatially distinct distribution of functional responses following somatosensory stimulation delivered to the mouth, wrists and ankles. The results suggest that as seen in animal studies, the human preterm period is likely to be critical for the development of the somatosensory system.

Gareth Ball, Richard Beare, Marc Seal

We  model the structural network architecture of the brain as a set of superposed subnetworks, or network components. We use non-negative matrix factorisation, an unsupervised and data-driven approach, to reliably identify separable subnetworks and track their development over the human lifespan. In the NKI-Rockland lifespan sample (n=196), we find evidence for an increased reliance on local communication between neighbouring regions, rather than through heavily-connected network hubs in older age. This method shows good potential for further exploration of the human structural connectome.

Gang Li, Li Wang, Weili Lin, John Gilmore, Dinggang Shen

An intrinsic relationship between surface area, cortical thickness and folding was found in adult mammalian brains across species, which was thought to relate to the mechanism of cortical folding. However, this relationship remains unclear in the dynamic developing human infant brains. To fill this gap, we jointly analyze surface area, cortical thickness and folding at birth, 1, and 2 years of age, using 219 longitudinal MRI scans from 73 infants. We reveal that the relationship between these cortical properties is gender-independent, but age-specific, with a substantial change in the first year and a subtle change in the second year.

Dingna Duan, Islem Rekik, Shunren Xia, Weili Lin, John H Gilmore, Dinggang Shen, Gang Li

Examining cortical folding development at various scales may help better understand brain cognition and motor functions. We propose a curvature-based multi-scale method using spherical wavelets to study the longitudinal changes of cortical folding during infancy. We applied our method on 219 longitudinal MR images from 73 healthy infants at 0, 1, and 2 years of age. We reveal scale-specific and region-specific developmental patterns of infant cortical folding. Specifically, at coarser levels, many primary folds flatten out; while at finer levels, the majority of the minor folds become more convoluted, providing new insights into early brain development.

Rali Dimitrova, Jonathan O'Muircheartaigh, Judit Ciarrusta, Dafnis Batalle, Emer Hughes, Johannes Steinweg, Emily Perry, Johanna Kangas, Ines Pote, Serena Counsell, Jo Hajnal, Declan Murphy, David Edwards, Grainne McAlonan

Thalamocortical development in early life is crucial for normal brain functioning and abnormalities to these networks are thought to underpin atypical neurodevelopment. However, to date examination of this system in the infant has been hampered by the lack of age-appropriate population atlases. In this study we circumvent this problem by applying independent component analysis to parcellate the thalamocortical projections and their underlying thalamic seed in 6-months-old infants using diffusion MRI.

Zhengwang Wu, Gang Li, Yu Meng, Li Wang, Weili Lin, Dinggang Shen

For the first time, a longitudinally consistent infant cortical surface atlas with densely-sampled 11 time points (at 1, 3, 6, 9, 12, 18, 24, 36, 48, 60, and 72 months of age) is built for better exploring the dynamic and critical early brain development, based on 339 serial MRI scans from 50 healthy infants. The longitudinal consistency and unbiasedness are ensured by an advanced two-stage group-wise surface registration during the atlas construction. To equip parcellations for our atlases, both the FreeSurfer parcellation (for coarse parcellation) and HCP MMP parcellation (for fine-grained parcellation) are mapped onto our infant atlases.

Farshid Sepehrband, Clio Gonzalez-Zacarias, Lu Zhao, Arthur Toga, Kristi Clark

Many studies have explored the relationship between neuroanatomical measures (such as cortical thickness or surface area) and cognition or health. Conventionally, generalized linear models are used to identify between-group differences within single measurements (e.g., regional cortical thickness), which ignores the possible interaction between neuroanatomical features. Incorporating a large number of regressors is not recommended in regression analyses, mainly due to the curse of dimensionality [1]. Multi-parametric classification approaches can be used to ameliorate the latter issue and to capture brain complexity [2]. The down side is that these approaches have less interpretability compared to regression techniques –because these techniques primarily focus on prediction accuracy rather than building an interpretable model. Here we present an approach that enables multi-parametric regression analysis by employing big data routine.

Huiying Kang, Qinmu Peng, Minhui Ouyang, Xiaolu Tang, Di Hu, Hong Zhang, Yun Peng, Hao Huang

Brain development in the first few years of life is dramatic. The microstructural changes of infant grey matter measured by mean kurtosis, a non-Gaussian diffusion metric more sensitive to cortical microstructure than traditional diffusion metric, is not known. This study recruited 16 typical developing 3-32-months-old infants to investigate microstructural changes of the cerebral cortex by using Diffusion Kurtosis Imaging (DKI). Our results showed positive correlation between the mean kurtosis (MK) value and age. Differentiated age-dependent MK increases among different cortical regions suggest spatiotemporally heterogeneous pattern in cortical development.

Benyamin Deldar, Emer Hughes, Nora Tusor, Serena Counsell, A. David Edwards, J-Donald Tournier

Myelination is an important aspect of brain development, but current myelin mapping techniques require extensive acquisition times and are therefore difficult to use routinely in neonates. In this study, we present results from a large cohort of neonates born preterm spanning a wide age range (26 to 125 weeks’ post-menstrual age) obtained using a recently proposed method that relies on existing routine data. Our results show good agreement with the expected spatial and temporal pattern of myelin formation over the age range studied, and may form the basis for future studies assessing myelin in the developing brain.

Jaeil Kim, Geng Chen, Pew-Thian Yap, Weili Lin, Dinggang Shen

In this abstract, we introduce a longitudinal diffusion-weighted infant brain atlas. For construction of this longitudinal atlas, we collected the diffusion-weighted images of 36 subjects, scanned at 5 time points (at neonate, 3, 6, 9 and 12 months of age). Our method builds the atlas from the diffusion-weighted images without the need for any diffusion models. Also, our method, based on patch-based sparse representation, preserves more structural details with spatial-temporal consistency in the longitudinal atlas. Thus, when applied to quantitative analysis of infant brain images, more accuracy can be achieved.

Giang-Chau Ngo, Clarisa Carruthers, Catherine Vu, Alex Cerjanic, Monica Muthaiya, Marie Drottar, Jonathan Litt, Ivan Frantz, Ryan Larsen, Borjan Gagoski, P. Ellen Grant, Bradley Sutton

Diffusion Tensor Imaging and Tract-Based Spatial Statistic on FA, RD and AD were applied to investigate white matter development in formula fed infants and breast fed infants. Thirty-six infants (thirty breast fed and six formula fed) were scanned at 1 month and twenty-two (twelve breast fed and ten formula fed) at 3 months. Increased FA and decreased RD values were observed in breast fed infants at 1 month with differences becoming insignificant at 3 months. 

Yao Wu, Diane Lanham, Samantha Bauer, Gilbert Vezina, Catherine Limperopoulos

The hippocampus plays an important role in stress regulation. This study aims to investigate the relationship between prenatal maternal stress and fetal hippocampal volumetric growth using magnetic resonance imaging (MRI). Results suggest that maternal depression and anxiety are associated with smaller left hippocampal volumes in female fetuses in the third trimester of pregnancy.

Vincent Lee, Alexander El-Ali, Alexandria Zahner, Kavita Vani, Vidya Rajagopalan, Michelle Gruss, Jennifer Adibi, Vincent Schmithorst, Ashok Panigrahy

We examined whether features of placental BOLD MRI in underlying setting of fetal congenital heart disease (CHD) differ from those of healthy controls, and the imaging data correlated with first trimester maternal serum markers (PAPP-A, β-hCG) known to influence vasculogenesis/angiogenesis.  We explored correlation between fetal brain resting stat networks and imaging and hormonal biomarkers of the placenta.  We used temporal, spatial, and spatio-temporal to analyze the squared-root-mean variance and distribution differences in BOLD signal between CHD and controls.  Difference in spatial and temporal BOLD signal variance is present in CHD pregnancies compared to healthy controls were observed.

Chao Jin, Yanyan Li, Xianjun Li, Miaomiao Wang, Congcong Liu, Jie Gao, Qinli Sun, Xiaocheng Wei, Jian Yang

Due to exposure to extrauterine environment, neonatal brain development is in totally different ways after birth, compared with the ‘protected’ gestation. However, little is known about the postnatal trajectory of neonatal brain development, especially for the differences between preterm and term neonates. This study aims to investigate the postnatal maturation of brain white matter (WM) during the neonatal stage and further provide comparison between preterm and term neonates. Our results suggest that during the neonatal stage, preterm neonates show weaker development capacity than term in optical and somatosensory functions, while present catching up maturation in motor function.

Sarina Karmacharya, Borjan Gagoski, Lipeng Ning, Martha Shenton, Ellen Grant, Yogesh Rathi

The study examined white matter (WM) abnormalities in neonates with Congenital Heart Disease (CHD) (19 CHD and 16 typically developing (TD) neonates). Gaussian mixture model showed that neonates with CHD have lower cellular volume and density in UF, SFOF, left IFOF, and CC.  Fractional Anisotropy was lower in neonates with CHD in bilateral UF, CC, and left SLF. NODDI results indicated lower intracellular volume in the bilateral SFOF, and higher fiber orientation dispersion in the left CC and SLF in CHD.  Our results demonstrate that significant WM abnormalities related to language areas are seen in neonates with CHD.  

Vincent Lee, Mark Greenhalgh, William Reynolds, Timothy Verstynen, Fang-Cheng Yeh, Cecilia Lo, Vincent Schmithorst, Ashok Panigrahy

We tested whether Multi-shell Multi-band Diffusion Imaging (MSMBDI) would be superior to standard DTI at delineating microstructural cortical association fiber abnormalities and predicting executive function preadolescents with complex congenital heart disease (CHD).  Using both a hypothesis-driven approach (manual tractography) and a data-driven approach (q-space diffeomorphic reconstruction) we examined white matter tracts in correlation with NIH Toolbox and complementary battery of neuropsychological test.  We show that MSMBDI – when compared to standard DTI – showed greater sensitivity towards white matter structure differences, superior at detecting microstructural differences in cortical association tracts in CHD compared to controls, and more predictive of executive deficits.

Dadi Zhao, Dantong Miao, Rui Shen, Feng Wang, Bing Zhu, Yu Sun, Bing Zhang

Neuroimaging for foetus brain is a challenging problem in which there are several issues to be solved. We proposed a general solution and finally reconstruct the lateral ventricle volume that is of great significance for clinical study. Firstly, slices were realigned to correct for the motion between acquisition of individual slices including transposition and rotation. Secondly, slices with motion artefacts were excluded and inconsistencies in intensity patterns resulting from the motion were estimated and corrected for. Thirdly, the structure of lateral ventricle was segmented via adaptive segmentation. Finally, the volume was reconstructed from irregularly sampled data.

Xin Mu, Hosung Kim, Duan Xu, Orit Glenn

Ventriculomegaly (VM) is the most common referred abnormality for fetal MRI and may be isolated or associated with additional abnormalities. We performed MR exams in 46 fetus diagnosed with isolated VM on ultrasound (US) and assessed neurodevelopmental outcome at 12 and 30 months with Bayley-III. Ventricle size (VS) measured by US and MRI and Bayley-III scores were analyzed using linear models. VS measured at older gestational age and longitudinal VS changes on MRI predicted outcome better than at younger age and on US. The presence of additional brain findings on fetal MRI significantly correlated with outcome and improved outcome predictability. 

Yogesh Rathi, Julia Cohen-Gilbert, Michael Rohan, Elizabeth Olson, Benjamin Reid, Sarina Karmacharya, Martha Shenton, Sion Harris, Marisa Silveri

Diffusion MRI (dMRI) is sensitive to microstructural arrangement of cells and axons in the brain. In this abstract, we analyzed dMRI data from 30 healthy children (14 girls, 13.9 ± 0.8 yrs, 16 boys, 13.4 ± 0.9 yrs). Advanced multi-tensor tractography was used to trace the SLF-II and heterogeneity in fractional anisotropy (HFA)4 (the standard deviation in FA) was computed in all subjects. Subjects were separated into two groups (males, females) and correlation between HFA and total Barratt Impulsivity Scores (BIS) was computed for each group. A statistically significant correlation was found between HFA in left SLF-II and BIS in girls but not in boys. The SLF-II has been known to be involved in spatial attention and executive control and higher heterogeneity in white matter integrity in SLF-II seems to be involved in impulsive/attentional network in young girls but not boys.

Jeong-Won Jeong

The aim of this study is to apply DTI-based connectome analysis to investigate the neural substrate and mechanism of picture exchange communication system (PECS) in young children with ASD. Seventeen non-verbal children with ASD who underwent PECS and 3T DTI (age: 3.05±0.82 years, 10 boys) were retrospectively selected for whole brain connectome analysis . Compared with 5 children who failed PECS (non-verbal after PECS), 12 children who succeeded PECS (verbal after PECS) showed significantly increased betweeness, local efficiency and nodal strength in anterior inferior occipital gyrus (p <0.01). Such increases may be an effective imaging marker to detect ASD children who will become verbal after PECS.  
 

Jing Zhang, Yunfei Zha, Guangyao Wu, GE healthcare China

IVIM diffusion is applied to detect the changes in the brain of  perinatally HIV-infected adolescents in our work. 18 children with HIV positive and 17 HIV negative children underwent MRI scan on a 3.0T whole body scanner including multi-b diffusion imaging. The IVIM parameters (D, D*and f ) were obtained by fitting using MITK software. Correlation of IVIM parameters and CD4+T cell counts, CD4/CD8 ratio were analyzed. D* value of caudate nucleus and frontal white matter decreased significantly in HIV positive children and the changes of D* were positively correlated with CD4+T cell counts and CD4/CD8 ratio. However,D and f were not statistically significant. IVIM improves on the detection brain damage in HIV infected asymptomatic adolescents as compared to conventional DWI.

Rob Dineen, Stefan Pszczolkowski, Felix Raschke, Hannah McGlashan, Manish Prasad, Gabriel Chow, William Whitehouse, Dorothee Auer

Cerebellar atrophy occurs in the inherited neurodegenerative syndrome Ataxia Telangiectasia (A-T) but the trajectory of cerebellar atrophy across childhood and its relationship to clinical status is unknown.  We report cerebellar and fourth ventricular volumes (normalized to intracranial volume) from 24 children with A-T and 24 matched controls.  Cerebellar volume declined linearly with increasing age in the A-T group with a divergent trajectory of age-related cerebellar volume change compared to normally-developing children.  Fourth ventricular volume increased with age in children with A-T and correlated with clinical status, and may provide an imaging marker of neurological status in childhood A-T.

Steffi Dreha-Kulaczewski, Hagen Kitzler, Hannes Wahl, Peter Dechent, Jutta Gärtner, Sean Deoni, Robert Steinfeld

Emerging clinical research in hypomyelinating leukodystrophies (HLD) necessitates definition of surrogate markers as endpoints in possible clinical trials. Standardized assessment of myelination using myelin sensitive MRI is therefore highly desirable. Proposed protocols comprise DTI, MT-imaging and myelin water imaging employing the mcDESPOT sequence. We report first experiences applying mcDEPSOT in patients with cerebral folate deficiency. Myelin water fraction (MWF) allowed assessment of subtle gradual and regional changes with sufficient spatial resolution. The extent of the myelin deficit in diffuse hypomyelination can more reliably be evaluated using the MWF parameter. McDESPOT seems a feasible, system independent method to study pediatric HLD.

Hua CHENG, YingZi GAO, Yang FAN, WenJing ZHANG, Yun PENG

Resting state-fMRI has been widely used as an effective method to evaluate the of brain functional changes in physiological and pathological process. Altered regional brain activities, especially in verbal and cognitive areas were found in children with nonsyndromic CL/P using resting-state fMRI. It helps to understand the abnormality of functional architecture of CL/P which implies different structures and cognitive patterns in CL/P compared with normal development children.

Bing Yu, Mingzhu Huang, Xu Zhang, Kaining Shi, Qiyong Guo

The study assessed the effects of (DRD4) -616 (rs747302) gene variation on gray matter volume (GMV) and arousal from sleep (AS) scores in children that suffered from primary nocturnal enuresis (PNE) and normal controls and found that The −616 C/G SNP in the DRD4 promoter may affect the AS scores and GMV in the thalamus and pregenual ACC in PNE children.

Adam Bernstein, Amber Pokorney, Harry Hu, Jeffrey Miller, Burris Duncan, Theodore Trouard

Cerebral Palsy is a nonprogressive condition that results in very heterogenous motor and other deficits that usually arises during the peripartum period. Many studies have tried to characterize changes in the brain of patients with cerebral palsy using fractional anisotropy and tractography based on diffusion tensor imaging, but few have utilized any of the more recent techniques, such as constrained spherical deconvolution, to more adequately account for complex fiber structures. These more recent techniques also offer more descriptive scalar measures of microstructure, such as apparent fiber density, that can be used to better characterize changes in neural structure.

DEFENG WANG, Jinpeng Li, YISHAN LUO, DANTONG MIAO, XIN ZHANG, Queenie Chan, Winnie CW CHU, LIN SHI, BING ZHANG

In this work, we proposed a transfer learning based FCN method which can automatically detect the fetal brain in MRI. We used the off-the-shelf model weights trained on nature images to initialize a fully connected network (FCN), and then fine-tuned the model on the fetal MRIs. We tested our method on two datasets with different MRI sequences, and the results demonstrated that the proposed method is automatic, fast and robust for detection of fetal brain in MRI.

Malek MAKKI, Ruth O'Gorman, Olivier Baledent, Philip Buhler, Markus Weiss, Christian Kellenberger, Ianina Scheer, Achim Schmitz

Anaesthetics such as those used for sedation in paediatric MRI affect cerebral blood flow and hemodynamics to varying degrees. This study examines the link between brain perfusion measured by arterial-spin-labelling and cerebral blood flow measured by phase-contrast MRI in 2 cohorts of children undergoing sedation either with propofol or a combination of propofol and ketamine. Significant correlations were observed between these 2 variables for both groups.

Zhouyang Lian, Shuixing Zhang, Kannie W.Y. Chan, Guanshu Liu

Most severe hand, foot, and mouth disease(HFMD) are caused by EV71 infections, which can result in central nervous system complications. So magnetic resonance imaging (MRI) acquisition is important for the patients with EV71 infection to reveal the location of lesions and select the potential severe cases with poor prognosis. We aim to reviewed MRI characteristics of the severe HFMD, using a multivariate approach to compare the prognosis of different lesion sites based on a large cohort with follow-up. Our findings suggested lesions located in medulla oblongata (P<0.015)and spinal cord(P<0.001) on MRI associated with poor prognosis.

Yi Liao, Haibo Qu, Xijian Chen, Chuan Fu, Yuexin Jiang, Gang Ning

Tourette syndrome is a neurobehavioral disorder characterized by motor and vocal tics beginning in childhood. Previous neuroimaging investigations suggested impaired cortico-striato-thalamo-cortical activity during motor control. We hypothesized that the small-world properties of functional connectomes would be abnormal in pediatric Tourette Syndrome patients. Compared with control subjects, the Tourette Syndrome patients showed altered quantitative values in the global properties, characterized by higher path length, higher normalized characteristic path length and lower global efficiency, implying a shift toward regular networks. The Tourette Syndrome group showed decreased nodal efficiency in the posterior part of left cingulum and right putamen comparing to the controls.

Chih-Hsien Tseng, Wuh-Liang Hwu, Yu-Jen Chen, Yun-Chin Hsu, Wen-Yih Tseng

Aromatic L-amino acid decarboxylase (AADC) deficiency is an inherited disorder that impairs synthesis of dopamine and serotonin. To investigate whether the white matter tracts are impaired in children with AADC deficiency, diffusion tensor imaging data were obtained from 7 children with AADC deficiency and 7 matched controls. Fractional anisotropy (FA) of 76 white matter tracts was measured and compared between the two groups. Fiber tracts of dopaminergic and serotonergic systems, and those connecting regions responsible for executive functions or regulating motor functions showed lower FA in patients. Our findings are consistent with clinical manifestations and pathophysiology of AADC deficiency.

Matt Gabel, Rebecca Broad, Daniel Alexander, Gary Zhang, Nigel Leigh, Mara Cercignani

Multimodal diffusion MRI and quantitative MT techniques were used to examine the nature of abnormalities in the corticospinal tracts (CSTs) of amyotrophic lateral sclerosis (ALS) patients.  Our data show reductions in axonal volume fraction (AVF) located superiorly to reductions in myelin volume fraction (MVF).  We also find extensive decreases in fiber volume fraction (FVF) throughout the entire CST, supporting the hypothesis of axonal loss as the primary pathological mechanism in ALS.

Cristah Artrip, Michael Pridemore, Jun Li, Richard Dortch

This study examines the sensitivity of DTI metrics to proximal sciatic nerve pathology in a cohort of patients with Charcot-Marie-Tooth (CMT) diseases and matched controls, with the longer-term goal of developing objective biomarker of disease progression and treatment response. Prior studies have shown that DTI metrics can relate to disability in other neuropathies. Here we demonstrate that robust DTI can be performed in the proximal sciatic nerve of patients with CMT, and the resulting metrics are sensitive to myelin and/or axonal pathologies. Future studies will test if DTI measures predict disability in patients with CMT.

Claudia Testa, Riccardo Gubellini, Stefano Zanigni, Lia Talozzi, Giulia Giannini, Giovanna Calandra-Buonaura, Pietro Cortelli, Daniel Remondini, Gastone Castellani, Paola Fantazzini, Claudio Bianchini, Stefania Evangelisti, Caterina Tonon, David Manners, Raffaele Lodi

We investigated the differences in global and regional topological properties and the modular organization of brain networks derived from anatomical covariance of structural MRI between Multiple System Atrophy patients (subdivided in the variants MSA-C, MSA-P) and healthy controls (HC). No differences were found in global, local and small-worldness measures between MSA and HC or between MSA-C and MSA-P. The investigation of modular organization, which reflects differences in properties that underlie the functionality of the brain, has shown a segregation in a cortical-subcortical motor network in patient groups, which may underpin both the typical parkinsonian and cerebellar features of the disorder.

Yu-Shiuan Liang, Ming-Ting Wu, Ching-Sen Shih, Ming-Chung Chou

Migraine subjects were demonstrated to exhibit white matter alterations detected by diffusion tensor imaging (DTI). Due to the Gaussian assumption of water distribution employed in DTI technique, the measured diffusivity may not be accurate and may hinder the detection of white matter alterations. Diffusion kurtosis imaging (DKI) was demonstrated to better characterize white matter alterations without Gaussian assumption and has not been utilized to detect white matter alterations in migraine subjects. This study performed DKI to detect microstructural white matter alterations and demonstrated that diffusion kurtosis parameters were more sensitive to subtle white matter alterations than diffusion tensor parameters.

Chih-Hsien Tseng, Wang-Tso Lee, Shinn-Forng Peng, Chien-Feng Huang, Yu-Jen Chen, Yun-Chin Hsu, Wen-Yih Tseng

To identify microstructural alteration of white matter tracts in patients with Tourette syndrome (TS), diffusion spectrum imaging data were obtained from 14 patients and 14 matched controls. Whole-brain tract-based automatic analysis was employed to investigate the differences in white matter microstructures between the two groups. As compared with the controls, patients with TS showed altered tract integrity in callosal fibers, cingulum, thalamic radiations and corticospinal tracts. The altered white matter tracts account for clinical hallmarks and pathophysiology of TS, and might serve as structural correlates of TS.

Tz-Yun Jan, Wang-Tso Lee, Shinn-Forng Peng, Isaac Wen-Yih Tseng

Rett syndrome (RTT) is characterized by trajectory changes in cognition and motor functions. To understand the disease-specific pathologic changes of each tract bundle in white matter in stable stage of RTT, we applied tract-specific analysis of the whole brain to investigate the alteration of 76 major tracts by diffusion spectrum image. In conclusion, the altered microstructural integrity in RTT were covered in whole brain, however, in systematically view, most of them were located in associative and commissure tract bundles. Surprisingly, the GFA value of anterior commissure in RTT was higher than controls, which might explain the well-preserved visual perception clinically.

Ju-Chien Wu, Jun-Cheng Weng, Jeng-Dau Tasi, Chao-Yu Shen, Shu-Li Wang

The products made by phthalate esters could be found everywhere. But there were only a few studies mentioned about the influence of phthalate esters exposure on brain volume. We used the voxel-based morphometry analysis to observe the correlation between the concentrations of maternal urine phthalate esters (MBP, MBzP, DEHP, MEHP, MEOHP) and children’s brain volume of gray and white matter. We found the negative correlation between the concentrations and the volume of frontal gyrus and cingulate gyrus.

Katherine Koenig, Se-Hong Oh, Melissa Stasko, Emma Lissemore, Elizabeth Roth, Anne Birnbaum, Thomas Scheidemantel, Hudson Taylor, Nancy Roizen, Stephen Ruedrich, Mark Lowe, Alberto Costa

This works uses 7 tesla MRI to assess resting state functional connectivity (rs-fMRI) in young adults with Down syndrome (DS). As compared to matched controls, individuals with DS show increased rs-fMRI in the default mode network, but decreased rs-fMRI in a network related to executive function.

Florian Borsodi, Valeriu Culea, Christian Langkammer, Michael Khalil, Lukas Pirpamer, Stefan Quasthoff, Christian Enzinger, Franz Fazekas, Stefan Ropele

Iron accumulation in deep gray matter occurs during normal aging, but has also been observed in several neurodegenerative diseases. To investigate if this still holds true for ALS, we aimed at assessing the iron content in deep gray matter structures of 24 ALS patients with quantitative susceptibility mapping and its relation to 28 controls. We did not find any significant differences in iron levels between ALS patients and controls. This may indicate that iron accumulation in deep gray matter is a specific feature that is not associated with neurodegenerative diseases in general, but rather reflects more specific degenerative processes.

Bo Hou, Dong-chao Shen, Pan Peng, Bo Cui, Xiao-lu Li, Hui You, Li-zhi Xie, Li-ying Cui, Feng Feng

This study was done to explore potential brain changes in ALS patients with different levels of cognitive deficits with voxel-based analysis of CBF generated by pCASL and VBM. Significant GM loss and CBF decrease were demonstrated in the severe frontotemporal dementia group. No difference of GM or CBF was found between ALS-Cn and ALS-Ci. Differences between ALS-Ci and ALS-FTD overlapped with those found between ALS-Cn and ALS-FTD, and the changes were more widespread in the latter contrast.

Xuan-Ru Zhang, Vincent Chin-Hung Chen, Dah-Cherng Yeh, Chao-Yu Shen, Jun-Cheng Weng

Breast cancer (BC) is one of the common public health problems, and chemotherapy was the major treatment for breast cancer. The previous study showed abnormal brain function was associated with the late effects of chemotherapy (5 to 10 years). The purpose of our study was to evaluate the early effects of post-chemotherapy BC patients (in 6 months). We investigated the resting-state functional differences between post-chemotherapy BC patients and healthy control. Our results provided the evidence of brain functional changes in women with breast cancer and highlight the importance of the breast cancer-related chemotherapy.

Qiuli Zhang, Haining Li, Yuchen Zhang, Dandan Zheng, Lijun Bai, Ming Zhang

Iron accumulation can induce a wide range of neuron disorders in central nerve system. Increased serum ferritin has been found to predict poor clinical outcome in ALS. We used quantitative susceptibility mapping to explore brain iron accumulation and theri clinical relevance. Increased iron level has been found in both cortical and subcortical motor related regions. The iron concentration in the primary motor cortex is responsible for deteriorated clinical syndrome, suggested its potential role for disease management. While increased iron concentration in the bilteral caudate contributed to impaired executive function, indicated network-based dysfunction for cognition decline in ALS.

Bhaswati Roy, Mary Woo, Gregg Fonarow, Ronald Harper, Rajesh Kumar

Heart Failure (HF) patients show gray matter injury in multiple brain areas, based on various MRI techniques; such injury can accompany loss of subcortical and white matter myelin integrity. However, the extent of regional myelin changes in HF is unclear. We examined regional myelin integrity in HF patients, and found decreased values, likely resulting from hypoxic/ischemic processes, in critical autonomic, cognitive, respiratory, and mood control sites. These functions are deficient in the condition. Myelin mapping, based on simple-to-calculate ratios of T1- and T2-weighted images, is useful for evaluating regional myelin changes.

Xin Chen, Tianyi Qian, Tobias Kober, Nan Chen, Kuncheng Li

High contrast in the lesion area is one of the most important prognostic factors for focal cortical dysplasia (FCD). The fluid and white-matter suppression (FLAWS) sequence provides two sets of 3D contrasts from one acquisition: one nulls the white-matter signal, the other nulls the cerebral spinal fluid signal. A new image (the FLAWS contrast) calculated from these two images may enhance the visualization of FCD lesion features, specifically the blurred grey-white matter interface and the transmantle sign. In this study, we assessed the ability of FLAWS to visualize FCD lesions. Our results demonstrate that FLAWS is sensitive to lesional tissue, especially the transmantle sign, providing additional value in MR-based FCD diagnostics.

Mary Finnegan, Matthew Grech-Sollars, Lesley Honeyfield, Philip Benjamin, Rebecca Quest, Edward Watson, Naz Nordin, Olivia Clancy, Ahmed Al-Hindawi, Agnes Nilsen, Ashley Mehmet, Klara Nenadlova, Lisa Williams, Trudi Edginton, Sara De Simoni, Marcela Vizcaychipi, Adam Waldman

We used advanced MR imaging methods to investigate neurophysiological changes following major burns injury in a cohort of patients with reduced cognitive function compared to age and sex-matched controls. In this preliminary study, small regions of increased connectivity were observed in patients in two brain networks extracted from resting-state fMRI data using ICA. However, the significance of these results is unclear given the broad range of neurological functions implicated by the cognitive deficits. Furthermore, we found no significant difference between patients and controls for TBSS, volumetric analysis and MR spectroscopy. SWI indicated large areas of microbleeds in one patient.

Nadya Pyatigorskaya, Rahul Gaurav, Claire Ewenczyk, Cecile Gallea, Romain Valabregue, Fatma Gargouri, Eric Bardinet, Isabelle Arnulf, Cyril Poupon, Marie Vidailhet, Stephane Lehericy

We used quantitative multimodal MRI to investigate the region-specific damage in progressive supranuclear palsy (PSP) in order to generate a precise model of neurodegeneration at various levels of the central nervous system, including brainstem nuclei, basal ganglia and cortex. PSP patients showed extensive volume decrease and microstructural diffusion changes in the brainstem and the basal ganglia in agreement with previous pathological studies. These results suggest the possibility of direct noninvasive assessment of brain damage in PSP not only in the basal ganglia and the cortex, as done previously, but also in small brainstem nuclei. 

Isaac Adanyeguh, Pierre-Gilles Henry, Vincent Perlbarg, Tra My Nguyen, Daisy Rinaldi, Celine Jauffret, Romain Valabregue, Uzay Emir, Dinesh Deelchand, Alexis Brice, Gulin Oz, Alexandra Durr, Fanny Mochel

Spinocerebellar ataxias (SCAs) are neurodegenerative disorders characterized by predominant atrophy of the cerebellum and pons, with the main symptom being ataxia. There is currently no treatment for this disorder due to the lack of robust biomarkers to evaluate the disease progression. This study aimed to identify robust biomarkers for this disorder using a combination of magnetic resonance spectroscopy and imaging techniques. This study confirmed neurometabolic alterations in SCAs as well as microstructural modifications resulting from the disease. This study also showed that imaging biomarkers are more sensitive to disease progression than clinical scores.

Nastaren Abad, Jens Rosenberg, Samuel Grant, Michael Harrington

The brain allocates >50% of its energy reserves to the regulation of sodium homeostasis, indicating the critical importance of sodium and its fluxes in normal brain and neurological disorders. The purpose of this study was to evaluate in vivo ²³Na in the brain using a rat model of migraine induced by nitroglycerin injection. The ultra-high field of 21.1 T was employed to quantify alterations in bulk sodium during and following the onset of central sensitization related to migraine. Multi-slice 2D CSI of sodium were acquired longitudinally to identify localized increases in sodium concentrations during a 3-h period following sensitization induction.

Lin Wang, Shenghong Ju

It is reported that the brain always be an injured target organ in end-stage renal disease (ESRD) patients, a series of pathophysiologic changes easily make the iron accumulate in brain and accelerate the brain degeneration, which results in the brain cognitive function decline. T1rho relaxation time can reflect the changes of the macromolecular substance content and can be shorten by the Paramagnetic component, which makes it the ability to distinguish the healthy controls from ESRD patients. Voxel based measurement as a classical methods to verify the volume of each brain section, which can be also used to represent the structure of the brain. Combined with the results of neuropsylogical tests, T1rho mapping can better characterize the hippocampus in ESRD patients and the conclusions give a support for considering that the brain function changes earlier than structure changes.

Sjoerd Vos, Caroline Micallef, Frederik Barkhof, Andrea Hill, John Duncan, Sebastien Ourselin

FLAIR is the single most sensitive MRI contrast to detect lesions underlying focal epilepsies but 3D sequences used to obtain isotropic high-resolution images are susceptible to motion. PROspective MOtion correction (PROMO) was applied to 3D-FLAIR scans in epilepsy patients to evaluate clinical benefit. Two radiologists reviewed 40 scans without and 80 with PROMO assessing six criteria on a seven-point Likert scale. PROMO scans can achieve near-identical image quality as nonPROMO scans, but intensity inhomogeneity was generally poor using PROMO. The percentage of scans with bad image quality was 4-fold lower with PROMO than without on the other five criteria.

Monika Dezortova, Vit Herynek, Julio Acosta-Cabronero, Lenka Kotackova, Daniela Zahorakova, Simon Robinson, Filip Jiru, Radan Bruha, Zdenek Marecek, Milan Hajek, Petr Dusek

Relaxometry and quantitative susceptibility mapping were used in patients with neurologic symptoms of Wilson disease (WD) that leads to copper metabolism disturbances and its gradual accumulation in liver and brain. These quantitative MR techniques revealed decreased T2 relaxation times in the basal ganglia, higher susceptibility in the deep gray matter nuclei and no T1 changes. It indicates presence of insoluble para- or superparamagnetic compounds, presumably in a form of hemosiderin. These deposits appear to be not related to the ceruloplasmin oxidase activity nor with the severity of neurological symptoms.

Kevin Lee, Sara Bohnert, Cory Vair, Ying Wu, John Mikler, Jeff Dunn

Chemical Warfare Nerve Agents (NAs) are toxic compounds that have the potential to cause mass casualty scenarios. The United Nation has categorized NAs as a weapon of mass destruction. The immediate and short-term effects of NA exposure is well understood, however, our understanding of the neurological effect at a sub-lethal dose is limited. We have found localized edema that may serve as a good biomarker to test novel treatments. 

Ming Zhou, Xiaobo Zhou, Xinyu Hu, Lu Lu, Lianqing Zhang, Jing Li, Jiayu Sun, Xiaoqi Huang

The current study aimed to use a novel graph-theory approach known as degree centrality to help diagnose methamphetamine abusers. Our findings identified increased degree centrality in right middle frontal gyrus, right inferior frontal gyrus and anterior cingulate cortex and degree centrality reductions were revealed in right superior parietal lobe and bilateral lingual gyrus. Additionally, decreased degree centrality of right lingual gyrus negatively correlated with the duration of methamphetamine abuse. Meanwhile, decreased degree centrality of right lingual gyrus might be a predictor of methamphetamine abuse duration with an acceptable diagnostic accuracy of 71%.

Bing Wu, Yi Yang, Shuai Zhou, Hai Song, Lubin Wang, Jianghong He, Zheng Yang, Xinhuai Wu

This study used 3D pseudo-continuous arterial spin labeling (pcASL) to compare cerebral blood flow (CBF) patterns in minimally conscious state (MCS) patients with those in vegetative state (VS) ones. The results identified different CBF patterns within specific brain regions in VS patients compared with MCS. ASL may serve as an adjunctive method to separate MCS from VS in DOC patients, and could be used in longitudinal assessments of patients with severe brain injuries.

Cheuk Ying Tang, Xiao Wei Chen, Saiming Cheng, Victoria Wang, Johnny C Ng, Edmund Wong, Zhen Lan Li

Task based fMRI and resting state scans were acquired on Persistent Vegetative State Patients before and after the administration of Amandatine.  Significant clusters of activation was detected post treatment.

Lalit Gupta, Paul Hofman, René Besseling, Jacobus Jansen, Walter Backes

The objective was to assess the time-signature of spontaneous BOLD brain fluctuations in patients with focal cortical dysplasia (FCD) and to compare these with other regions and healthy controls. Whole cerebrum resting-state functional MRI time-series were analyzed using three different BOLD measures: wavelet entropy, regional homogeneity and fractional amplitude of low frequency fluctuations. All the three BOLD measures indicated attenuated low frequency oscillations in FCD lesions compared to controls. Also abnormal BOLD activity was found in the proximal and contralateral region, which can complicate the interpretation on what regions are functionally normal, functionally connected or abnormal in patients with FCD.

Paulo Rodrigues, David Moreno-Dominguez, Marc Ramos, Pablo Villoslada, David Gallardo-Pujol, Vesna Prckovska

Very little is known on how the entrepreneurial brain works. While previous work has examined only certain personality traits at a time, some of which are discussed here, this work aims to take an overall view of the traits found in an entrepreneur (determined by psychometric evaluations) and compare these to structural connectivity levels and cortical volumes in certain areas of the brain.

Roy Haast, Dimo Ivanov, Jacobus Jansen, Hubert Smeets, Irenaeus de Coo, Elia Formisano, Kâmil Uludag

The m.3242A>G mitochondrial mutation is known to cause the MELAS syndrome. A group of MELAS patients was scanned using multi-parameter quantitative 7T MRI to assess brain changes related to mutation load and disease duration. Here, we focused on cortical thickness differences between control subjects and MELAS patients and within patients as a function of mutation load. MELAS patients were characterized by a reduced cortical thickness compared to control subjects in several regions. Within these regions, cortical thickness decreases with increasing mutation load for the fusiform and planum temporal gyri, which are involved in visual working memory and auditory processing, respectively.

Gosuke Okubo, Tomohisa Okada, Akira Yamamoto, Yasutaka Fushimi, Tsutomu Okada, Kaori Togashi

Correlation was investigated between normal aging and T1 relaxation time in the deep gray matter with MP2RAGE sequence using voxel-based analysis (VBA) and regions-of-interest (ROIs) focusing on the deep gray matter (GM). Seventy healthy subjects were included. In VBA, linear correlation was explored, whereas second order regression was added in ROI analysis. The results showed relationship that varied among deep GM structures. Those findings will shed light on further investigation of T1 relaxation time in patient groups.

Gisela Hagberg, Jonas Bause, Thomas Ethofer, Philipp Ehses, Thomas Dresler, Cornelia Herbert, Rolf Pohmann, gunamony Shajan, Andreas Fallgatter, Marina Pavlova, Klaus Scheffler

Detection of subtle variation of the myeloarchitecture within the cerebral cortex may be feasibile with high-field mapping of the longitudinal relaxation time. However, besides myelin other factors like iron or variation of the grey matter volume may impact this MR parameter. In the present work we propose a model that includes and quantifies these factors. We found a regionally dependent, continuous increase from early adulthood into the middle ages that tentatively can be assigned to myelin.

Kyung Mi Lee, Hyug-Gi Kim, Sung Kyoung Moon, Eui Jong Kim, Woo Suk Choi

White matter hyperintensities (WMH) is one of the important characteristics of cerebral small vessel disease (cSVD). To diagnosis individual WMH evaluation method and investigate the degree of WMH form using MR image, we proposed that machine learning based on WMH group classification and individual diagnosis system.

Yue Xing, Abdul Sapuan, Robert Dineen, Andrew Cooper, Dorothee Auer

Rapid neuromelanin-weighted MR imaging sequence was performed to noninvasively inspect the physiological changes of substantial nigra and Locus ceruleus across a wide range of age in healthy subjects using neuromelanin-sensitive MRI for the first time. 

Yawen Sun, Yan Zhou, Yao Wang, Xu Han, Weina Ding, Yong Zhang, Qun Xu, Jianrong Xu

The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) or their effects on cognition has rarely been investigated. The purposes of the present study were to investigate brain iron deposition in deep gray matter nuclei in svMCI patients using quantitative susceptibility mapping (QSM) and its correlation with the severity of cognitive impairment. Susceptibility values were found to be elevated within bilateral hippocampus and right putamen in svMCI group compared with controls, which were related to cognitive measurements. Our result suggests that brain iron deposition which relation to cognition indicates the clinical relevance of the biomarker.

Subin Lee, Hyunna Lee, Heesoog Kim, Ki Woong Kim

Development of sensitive markers that can detect Alzheimer’s Disease at its pre-dementia stages is of critical importance. We hypothesized that altered cytoarchitecture caused by AD pathology would lead to a subtle altered pattern of voxel intensities on MRI which could be detected by texture analysis. In a training set of 111 AD and 141 normal controls, we extracted a set of texture features from core regions affected by pathology – precuneus, posterior cingulate cortex, hippocampus – that could efficiently discriminate between the two groups(AUC=0.875, p<0.001) as well as predict MCI/AD conversion from the normal stage (AUC=0.716, p=0.031).

Heisoog Kim, Jiwon Han, Hyunna Lee, Ki Kim

The areas in cerebral white matter appearing hyperintense on T2-weighted and fluid-attenuated inverse recovery (FLAIR) MRI are commonly referred to as white matter lesions (WMLs). Diverse scores and rating systems have been used for evaluating WMLs. However, these visual rating scales are still qualitative and subjective, leading to low reliability and reproducibility. The purpose of this study is to investigate the relation between cognitive functions and WMLs clustered by their profiles of distance from the ventricle, establishing the quantitative and objective evaluation of WMLs.

Kouhei Kamiya, Masaaki Hori, Ryusuke Irie, Masakazu Miyajima, Madoka Nakajima, Koji Kamagata, Kouhei Tsuruta, Yuichi Suzuki, Asami Saito, Misaki Nakazawa, Harushi Mori, Akira Kunimatsu, Hajime Arai, Shigeki Aoki, Osamu Abe

Microstructural changes of the corticospinal tract (CST) in idiopathic normal pressure hydrocephalus (iNPH) before and after CSF shunt surgery were studied using NODDI and WMTI. Pathological increase of orientational coherence and its postoperative normalization were shown, indicating axon stretching and its recovery. To the contrary, decrease of axon density was present in iNPH and remained after the surgery. Simulation using undulating cylinder model demonstrated both NODDI and WMTI can separate the effects from axon density and undulation. These results suggest possibilities of diffusion MRI to distinguish between reversible and irreversible microstructural changes in iNPH, and raise expectation for prediction of treatment outcome.

Chia-Feng Lu, Wen-Jin Hsieh, Yu-Chieh Jill Kao, Paul Blakeley, Fei-Ting Hsu, Hua-Shan Liu, Ping-Huei Tsai, Li-Chun Hsieh, Cheng-Yu Chen

The change of whole-brain connectivity during resting state can be a reliable feature in discriminating patients with Alzheimer’s disease (AD) from patients with mild cognitive impairment and cognitively healthy elders. Significant correlations between resting-state functional connectivity and cognitive decline measured by Mini-Mental State Examination (MMSE) were further identified.

Mustapha Bouhrara, David Reiter, Christopher Bergeron, Linda Zukley, Susan Resnick, Stephanie Studenski, Josephine Egan, Luigi Ferrucci, Richard Spencer

An emerging hypothesis suggests that the underlying pathophysiology of mild cognitive impairment (MCI) involves alterations in brain myelination. These alterations may represent an important correlate of dementia. Several studies have examined this correlation; however, these earlier analyses were performed using non-myelin-specific methods such as relaxation times, magnetization transfer and diffusion. This greatly complicates the interpretation of such imaging results in terms of myelin content. Our results show direct evidence of MWF alterations and loss in MCI using a direct measure of myelin-bound water. 

Jakob Meineke, Fabian Wenzel, Iain Wilkinson, Ulrich Katscher

Quantitative Susceptibility Mapping (QSM) and volumetry are used to study the deep gray-matter nuclei of patients with Alzheimer’s Disease (AD) and healthy control subjects. QSM is performed using “Joint background-field removal and segmentation-Enhanced Dipole Inversion” (JEDI), which leverages the information from automated model-based segmentation and allows the compact single-step formulation of the ill-posed inversion problem of QSM. For comparison QSM is also performed using L1-MEDI from the MEDI-Toolbox. The tissue magnetic susceptibility shows no significant difference between the Alzheimer group compared to the healthy control group. In contrast, the normalized volume of segmented gray-matter regions is significantly reduced in AD patients.

Scott Thalman, David Powell, Andrew Shen, Anika Hartz, Ai-Ling Lin

In this study we determine the blood-brain partition coefficient (BBPC) in aging C57Bl6/N mice and the transgenic 129S6/Tg2576 mouse model of Alzheimer’s disease using a calibrated proton density imaging approach. Aging mice demonstrate a 5.5% reduction in BBPC compared to young mice (0.94±0.04 mL/g vs 0.99±0.04 mL/g, p = 0.02), however Tg2576+ mice preliminarily demonstrate an elevated BBPC compared to wild-type controls (01.03±0.04 mL/g vs 1.00±0.05 mL/g). These high quality BBPC maps acquired much faster than previously reported could potentially be used to correct cerebral blood flow measurements derived from arterial spin labeling.

Satoshi Nakajima, Susumu Mori, Kaori Togashi, Kenichi Oishi

The Clock-Drawing Test (CDT) is used to screen and select cognitively impaired individuals for further evaluation. For the clinical interpretation of the CDT, an understanding of the neuroanatomical substrates that account for a decline in the CDT score is essential. We investigated the relationships between regional volume loss and a decline in the CDT score in two years. Atrophy in the left prefrontal and middle-occipital gyri was correlated with a decline in the CDT score. The result validated the use of the CDT, combined with memory tests that evaluate parieto-temporal functions, as part of an overall cognitive screening.

Tao Zhou, Kim-Han Thung, Dinggang Shen

Studies have shown that neuroimaging data (e.g., MRI, PET) and genetic data (e.g., SNP) are associated with the Alzheimer’s Disease (AD). However, to achieve a more accurate AD diagnosis model using these data is challenging, as these data are heterogeneous and high-dimensional. Thus, we first used region-of-interest based features and deep feature learning to reduce the dimension of the neuroimaging and SNP data, respectively. Then we proposed a deep cross-modal feature learning and fusion framework to fuse the high-level features of these data. Experimental results show that our method using MRI+PET+SNP data outperforms other comparison methods.

Bénédicte Maréchal, Peipeng Liang, Lin Shi, Tianyi Qian, Defeng Wang, Tobias Kober, Alexis Roche, Kuncheng Li

We investigate the potential of a Chinese-specific brain atlas derived from a large MR database of healthy  Chinese subjects to accurately support Alzheimer’s Disease diagnosis using automated brain volumetry in the Chinese population. Our experiments show that disease detection sensitivity is higher than when using either a Westerner-specific atlas and normative ranges or combining a Westerner atlas with Chinese-specific normative ranges. These findings suggest that population-specific models improve the reliability of medical decision support systems based on automated brain volumetry.

Zhizheng Zhuo, Zhuqing Long, Bin Jing, Xiangyu Ma, Han Liu, Jianxin Dong, Xiao Mo, Qi Yan, Haiyun Li

MCI (Mild Cognitive Impairment) is a pre-stage of Alzheimer’s Disease (AD). And the early detection of MCI is important for early treatment of AD patients. In this work, prediction efficiency of early stage of AD based on the functional connectivity network characteristics was evaluated by using a couple of classifiers with AAL_90 and AAL_1024 templates. The results showed that brain functional characteristics were effective in the prediction of MCI with a SVM-based classifier. And a more fine template could improve prediction accuracy.

Yi Shan, Yunpeng Bian, Zhiqun Wang, Zhilian Zhao, Mo Zhang, Jie Lu, Kuncheng Li

Acupuncture has been a major therapeutic method in Chinese medicine for treating Alzheimer’s disease (AD) with validation and safety. In this study, we use functional magnetic resonance imaging (fMRI) to investigate the acupoint-specific effect of acupuncture in treating for AD.  We found acupuncture at real acupoints activated brain areas primarily in the left uvula, right superior temporal gyrus and right uncus, while acupuncture at sham acupoints only activated areas in the left insula. These results showed that acupoint-specific effect of acupuncture presented by fMRI may help to facilitate its clinical use in AD treatment.

Xiaoqing Ji, Haiyang Geng, Rui Li, Le He, Chun Yuan

In this study, we used graph theory-based approaches to explore the topological organization of whole brain network in Alzheimer’s Disease. We performed resting state fMRI on 6 AD patients and 19 normal controls. Topological properties such as small-world, efficiency and nodal centrality were calculated and nonparametric permutation tests were further used for group comparisons. The results showed that high-level cognitive regions including parietal cortex, vmPFC, precuneus and emotional regions including caudate and thalamus were changed in the topological metrics, this may be a biomarker for AD classification. 

Toshiaki Taoka, Yoshitaka Masutani, Hisashi Kawai, Toshiki Nakane, Kiwamu Matsuoka, Fumihiko Yasuno, Shinji Naganawa

We tried to evaluate the activity of human glymphatic system by diffusion images. Our subjects were Alzheimer's disease (AD), in which it is known that the activity of the glymphatic system is impaired in animal experiments. We evaluated the diffusivity along the perivascular spaces as well as projection fibers and association fibers, and correlated them with MMSE score. There were significant positive correlation between diffusivity along perivascular spaces and MMSE score, indicating impaired water diffusivity related to AD severity. Our result may indicate that activity of the glymphatic system can be evaluated by diffusion images.

Jin Shang, Liu Yingqiu, Yanwei Miao, weiwei wang

EPVS may reflect underlying cerebral small vessel disease. We assumed the presence of EPVS were associated with cerebral blood flow (CBF)reduction ,and can accurately reflect the cognitive state.The study verifies a good coherence between EPVS and CBF in BG and CS of AD patients , and furthermore reflects of EPVS as the biomarker of cognitive status to a certain extent.

Parshant Sehrawat, H. Michael Gach, Wenna Duan, Andrea Gillman, James T. Becker, Oscar L. Lopez, Weiying Dai

Biomarkers for Alzheimer’s disease (AD) are crucial for early diagnosis and treatment monitoring once therapies become available. In this study, the spin-lattice relaxation time in the rotating frame with (T_1sat) and without (T_1nosat) off-resonance saturation was measured at 1.5 T in the cardiovascular health study cognition study cohort. Cross-sectional and longitudinal studies of the normalized difference (ΔT_1RF) between T_1sat and T_1nosat revealed regions of statistical significance in the brain that are associated with dementia pathogenesis. ΔT_1RF changes in the thalamus were consistent for the cross-sectional and longitudinal studies, indicating that ΔT_1RF could be a promising imaging biomarker for AD. 

Azhaar Ashraf, Dr Po-Wah So

The aim of the study was to characterise the relationship between cerebrospinal fluid (CSF) iron regulatory proteins (ferritin, ceruloplasmin), neuroinflammation and MRI-derived hippocampal volume in healthy controls, mild cognitive impairment and Alzheimer’s disease subjects. Ceruloplasmin positively correlated with neuroinflammation and ferritin in MCI and AD while in the latter group, it was negatively correlated with hippocampal volume. Ferritin positively correlated with neuroinflammation in HC and AD but also with tau levels in MCI. Iron dyshomeostasis, neuroinflammation and tau metabolism may increase hippocampal atrophy and aggravate AD pathogenesis.        

Hui Zhang, Joseph Shiu-Kwong Kwan, Pui-Wai Chiu, Edward S. Hui, Queenie Chan, Henry Ka-Fung Mak

Brain imaging research has elucidated the structural and functional changes at the clinical stages of AD and MCI, however, the characteristics of resting-state functional connectivity of SCI are largely unstudied. Hippocampus is among the first regions targeted by AD pathology. In this study, we employed resting state fMRI to study the connectivity between hippocampus and posterior cingulate cortex in SCI, MCI and AD groups.  In the preliminary results, the connectivity between hippocampus and PCC in SCI was found stronger than control and other two neurodegenerative groups which may suggest that compensatory mechanisms providing preserved hippocampal pathway in SCI.

Jiri van Bergen, Xu Li, Frances-Catherine Quevenco, Sandra Leh, Anton Gietl, Valerie Treyer, Rafeal Meyer, Alfred Buck, Roger Nitsch, Peter van Zijl, Christoph Hock, Paul Unschuld

To investigate whether brain iron load has an impact on Aβ associated functional brain change, this study investigated a large sample of cognitively healthy adults including 44 Super-Agers (subjects over the age of 85 without cognitive impairments) using simultaneous assessment of Amyloid-PET for Aβ-plaque-density, QSM for estimation of iron load and resting-state-fMRI.

Our findings indicate that the combination of Aβ-plaque-density with other neurodegenerative change (iron), has an impact on brain functionality, reflected by significant changes of resting state functional connectivity. Additionally, Aβ-plaque-density had no significant effect on functional connectivity in Super-Agers.

Shujuan Fan, Yajun Ma, Xing Lv, Jiang Du, Graeme Bydder, Nikolaus Szeverenyi

The use of subtracted STIR images designed to null white and gray matter respectively is illustrated in formalin fixed brain samples at 11.7T. The images show the normal layers of the cerebral cortex with high contrast. The layers were less well seen, or not seen at all in Alzheimer’s Disease samples. Use of MT pulses with the STIR sequences produces high positive and negative contrast on difference images. The STIR subtraction technique made have general application, and be used with different forms of data acquisition. It may also be useful in other clinical situations for demonstrating changes due to small differences in T1 in the presence of long T1 fluids. 

Mina Park, Yeonsil Moon, Seol-Heui Han, Won-Jin Moon

We evaluated the prevalence and its associated risk factors of motor cortex hypointensity on SWI in cognitive impaired patients. This retrospective study included 116 cognitively impaired patients (28 Alzheimer disease patients and 88 mild cognitive impaired patients). Among them, 83 patients showed positive motor cortex hypointensity on SWI and it was associated with age. Furthermore, the group with positive motor cortex hypointensity on SWI had less APOE4 allele carriers than negative group and this shows (+) APOE4 allele may act as an accelerating factor of cognitive decline even before iron accumulation starts to show changes in the motor cortex.

Junjie Wu, Ganesh Chand, Om Sharma, Deqiang Qiu, Ihab Hajjar

We examined racial differences in cerebrovascular reactivity (CVR) to carbon dioxide and their associations with cognitive function among patients with mild cognitive impairment and hypertension. The results provide evidence for association between impaired CVR and executive dysfunction. Hypertensive African Americans have more compromised cerebral microcirculatory function compared to Caucasians.

Jun Hua, M Wyss, J. M. G. van Bergen, S. J. Schreiner, S. C. Steininger, A. F. Gietl, A. Buck, R. M. Nitsch, K. P. Pruessmann, H. Lu, P. C. M. van Zijl, M. Albert, C. Hock, P. G. Unschuld

Progressive impairment in multiple cognitive domains is a clinical hallmark of Alzheimer’s Disease (AD), which is the most frequent cause for dementia in the elderly and is neuropathologically characterized by both cerebral β-amyloid (Aβ) accumulation and microvascular abnormalities. Here, we report significant co-localization of regions with microvascular abnormalities measured by arteriolar-cerebral-blood-volume (CBVa) MRI and Aβ accumulation measured by PiB-PET in elderly subjects at-risk for AD. Multiple regression analysis suggested that CBVa and Aβ may have a synergistic effect on longitudinal cognitive decline in these subjects . Both variables may need to be considered for secondary prevention trials in such populations.

Dewen Meng, Akram Hosseini, Richard Simpson, Robert Dineen, Dorothee Auer

This study investigated the association between functional disconnection of cognitive networks, structural disconnection indexed as microscopic damage of specific white matter tracts, and global cognitive impairment in symptomatic carotid artery disease. The findings regarding the mediating effects of functional disconnection on the association between structural disconnection and global cognitive impairment provided promising implications for future studies that develop therapies for patients with vascular cognitive disorder.

Bing Zhang, Bin Zhu, Yun Xu, Qing.X Yang

Olfactory deficits have been observed in subjects with Alzheimer’s disease (AD) and its potential as a biomarker has been demonstrated by several recent studies. However, its sensitivity and specificity in detecting early AD have not been validated in the Chinese population where aging population is growing rapidly. In this study, by using a 3.0 T MR scanner, we evaluate the presence of olfactory deficits and hippocampal volume loss measured by FreeSurfer (6.0) based on local population in China, to validate the use of olfactory test battery as a clinical AD marker.

Lei Du, Yijiang Zhu, Tianbin Song, Lizhi Xie, Guolin Ma

Based on gradient echo (GRE) magnetic resonance phase data, quantitative susceptibility mapping (QSM) is a novel technique which allows the non-invasive  assessment of magnetic tissue susceptibility distribution in mild alzheimer’s disease (AD). In this study ,we investigated the correlation between mini-mental state examination (MMSE) and bulk tissue magnetic susceptibility in subcortical nuclei of 14 mild AD subjects and 14 cognitively healthy controls scanned at 3T . A strong linear correlation between them was found in caudate nucleus and dentate nucleus. Hence, QSM can be used for early AD diagnosis and intervention.

Christine Tardif, Robert Amaral, Gabriel Devenyi, Pedro Rosa-Neto, Judes Poirier, John Breitner, M Mallar Chakravarty, The PREVENT-AD Research Group

Cerebrospinal fluid (CSF) β-amyloid and phosphorylated-tau are consistently used as biomarkers related to the pathophysiology and clinical severity of individuals in the earliest phases of Alzheimer’s disease (AD). This study shows that T1-weighted and FLAIR signal intensity in the hippocampal subfields, normalized using the fimbria, are associated with ApoE4 status and CSF biomarkers. The FLAIR results suggest that presence of inflammation in the subiculum of ApoE4 carriers and in the CA1 and molecular layers of the hippocampus in subjects with low CSF β-amyloid burden as tau pathology increases.

Yi-Tien Li, Chun-Yuan Chang, Yi-Cheng Hsu, Jong-Ling Fuh, Fa-Hsuan Lin

This study quantified the impact of physiological noise correction in characterizing the resting-state fMRI in Alzheimer’s disease (AD) patients with age- and gender-matched 17 healthy subjects and 15 AD patients. Using a seed-based correlation method with seeds at posterior cingular cortex and medial prefrontal cortex, we found that the difference in the functional connectivity between AD patients and healthy controls was significantly reduced when physiological noise was suppressed. 

Bruno Vieira, Carlos Salmon

The aging process entails morphological and functional alterations in the human brain. Using magnetic resonance imaging data of 130 subjects aged between 18 and 81 years from a publicly available dataset we obtained whole brain cortical thickness estimates and resting state connectivity to study how healthy aging affects these. Additionally, we studied the relationship between cortical thickness and functional connectivity. A heterogeneous thinning profile was observed and also a dominance in increases in connectivity, with few decreases. Connectivity correlates with thickness with temporal and occipital seed ROIs. These results might help to understand how connectivity and thickness relate in neuropathologies.

Vineela Gandham, William Meilandt, Kai Barck, Maj Hedehus, Kimberly Malesky, Claire Pichon, Oded Foreman, Gai Ayalon, Kimberly Scearce-Levie, Richard Carano

The PS2APP, PS2APPxTau_P301L^Het, Tau_P301L^Homo, Tau_P301L^Het transgenic mouse models of AD were characterized using MRI, and various regional brain atrophies were detected using a completely automated analysis by SPM-8. Furthermore, through MRI (both ROI and voxel based morphometry) and histology we showed that the presence of PS2APP mutation in PS2APPxTau_P301L^Het triple transgenic mouse model exaggerates the Tau pathology.  The presented results will enable MRI as a great tool to non-invasively assess the disease progression over time in preclinical therapeutic studies targeting Aβ and Tau pathology.

Chantal Sopacua, Arnold Evia, Aikaterini Kotrotsou, Sue Leurgans, David Bennett, Julie Schneider, Konstantinos Arfanakis

White matter hyperintensities (WMH) are white matter lesions appearing hyperintense in T2-weighted MRI. WMH are common in older adults and have been associated with increased risk of cognitive decline and dementia. Previous efforts have attempted to identify the neuropathologies associated with whole brain WMH burden. However, it is yet to be determined if the relationship between regional WMH burden and age-related neuropathologies is the same, or varies, in different parts of the brain. Therefore, the purpose of this research was to investigate the association between regional WMH burden and neuropathologies in a community cohort of older adults.

Philipp Boehm-Sturm, Joseph Kuchling, Susanne Mueller, Marco Foddis, Carsten Finke, Celeste Sassi, Christoph Harms, Stefan Koch, Ulrich Dirnagl, Tracy Farr

Chronic mouse brain hypoperfusion produces white matter damage; a feature of vascular cognitive impairment. Despite growing interest in this model, we have struggled to observe a strong phenotype. The present study aimed to improve the phenotype through extended hypoperfusion (6m). We examined the effect on various MR biomarkers including functional connectivity and vascular remodeling. We found massive structural changes including arterial neovessels, small subcortical strokes, and microbleeds. Animals showed behavioral deficits accompanied by changes in resting state MRI signals of the cingulate cortex, which is functionally connected to regions related to behavior (hippocampus) and emotion (amygdala).

Arman Kulkarni, Arnold Evia, Julie Schneider, David Bennett, Konstantinos Arfanakis

White matter hyperintensities (WMH) are commonly observed in brain MR images of older adults. Recently, more and more research studies assess WMH burden using ex-vivo MRI, aiming at directly linking WMH to the underlying neuropathologies detected at autopsy. The purpose of this work was twofold: 1) to investigate the relationship between WMH burden assessed in-vivo and ex-vivo on the same older adults, and 2) to test the hypothesis that WMH burden assessed ex-vivo is higher than that assessed in-vivo for longer ante-mortem intervals (AMI) (i.e. from in-vivo MRI to death).

Gabriel Mangeat, Benjamin De Leener, Virginija Danylaité Karrenbauer, Marcel Warntjes, Nikola Stikov, Caterina Mainero, Julien Cohen-Adad, Tobias Granberg

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and multiple sclerosis (MS) are demyelinating and neurodegenerative disorders that can be hard to distinguish clinically and radiologically. Here, we present a framework to extract independent physiological sources of signal from time-efficient multiple quantitative relaxometry (T1, T2 and PD maps) to characterize varying degrees and mechanisms of tissue disruption. The method can aid in the differentiation of HDLS and MS (p=0.007), as well as identify MS subtypes (p=0.0007), which would be helpful in ensuring a correct diagnosis and treatment of these disorders.

Kathryn Broadhouse, Chao Suo, Maria Fiatarone Singh, Nicola Gates, Wei Wen, Perminder Sachdev, Henry Brodaty, Nidhi Saigal, Nalin Singh, Guy Wilson, Jacinda Meiklejohn, Bernhard Baune, Michael Baker, Nasmin Foroughi, Yi Wang, Yorgi Marvos, Michael Valenzuela

Mild cognitive impairment (MCI) increases future risk of dementia, however, several studies have shown that mental and physical exercise reduce this risk. From the Study of Mental Activity and Resistance Training (SMART) we have previously shown significantly improved global cognitive function immediately after 6 months of progressive resistance training in MCI. In this analysis, we compare longitudinal hippocampal volume change in MCI using linear mixed effects models over an 18-month period comprised of a 6-month training phase and a 12-month post training follow-up. Our results show both isolated cognitive and progressive resistance training significantly diminished the rate of left hippocampal atrophy compared to a double sham intervention across training and an extended follow-up period.

Xiaobo Chen, Han Zhang, Lichi Zhang, Dinggang Shen

In this abstract, we show that the diagnosis accuracy of mild cognitive impairment (MCI) can be significantly improved by integrating dynamic information contained in the traditional functional connectivity (FC) from grey matter (GM) regions and the functional correlation tensors (FCT) from white matter (WM) regions, both computed from resting-state fMRI (RS-fMRI). The advantages of our method include: 1) dynamic FC is exploited to reveal rich time-varying information in FC, and 2) the anatomical structure information within WM can be well incorporated in RS-fMRI.

Carina Graf, Erin MacMillan, John Kramer, Cornelia Laule

We investigated metabolites in the anterior cingulate cortex using magnetic resonance spectroscopy in individuals with spinal cord injury (SCI). Short-TE PRESS at 3T provided reliable fits for glutamate (Glu), N-Acetyl-aspartate (NAA), total creatine (tCr), myo-Inositol and total choline. SCI patients had 11.3 % less Glu. Given the role of Glu in synaptic transmission between neurons and also between neurons and oligodendrocytes, reduced Glu in SCI may reflect decreased synaptic density and activity due to a loss of sensory input in the anterior cingulate cortex. Further research investigating the effect of sensory input loss on metabolite concentrations in SCI is warranted.

Maryam Seif, Patrick Grabher, Alan Thompson, Armin Curt, Patrick Freund

Spinal cord injury (SCI) leads to immediate sensorimotor and autonomic dysfunction and SCI patients generally show little clinical recovery within the first year after injury. Early structural changes at the spinal and brain level and their interactions with recovery rate are not well understood. The aim of our study was to reveal trauma-induced neurodegeneration and its interaction to impairment within early stage after injury employing quantitative neuroimaging technique. Our finding showed that significant atrophy and microstructural changes initiated in neural sensorimotor system within already early stage after SCI and quantitative neuroimaging methods hold potential to disclosing these neurodegeneration mechanisms. 
 

Maryam Seif, Gabriel Ziegler , Patrick Freund

Following Spinal Cord Injury the sensorimotor and limbic system immediately undergo progressive neurodegeneration (atrophy). Next to the focal grey and white matter atrophy, localized CSF and ventricular volume changes may provide additional biomarkers for brain atrophy. We therefore aimed to track brain atrophy by means of CSF volume changes and ventricular enlargements over two years following SCI. Our finding showed an increase of local CSF volume as well as ventricles enlargement in patients over time. The  CSF volume which is normally used as a biomarker of general atrophy, showed also sensitivity to local degenerative changes in SCI.

Bhanu Prakash KN, Sanjay Verma, Andrew Maudsley, Sendhil Velan S

Traumatic brain injury (TBI) results in a broad spectrum of symptoms and disabilities and has a high rate of mortality and morbidity. TBI is associated with elevated brain temperature due to inflammation. TBI has heterogeneous consequences of pathophysiology, changed intracranial dynamics and cerebral metabolism. In some cases there is an increase in ICP and cerebral perfusion which makes the management of the injury difficult .   Therapeutic hypothermia is recommended as one of the acute management techniques as it increases neuroprotection, decreases cerebral metabolism and ICP. To induce hypothermia and monitor the brain temperature a noninvasive and accurate assessment of cerebral temperature is essential. MR based temperature measurement based on the water resonance frequency, relaxation times (T1, T2), spectroscopy, proton density, diffusion etc. have been widely used. Echo-planar spectroscopic imaging (EPSI) method has the advantage of simultaneous acquisition of water and spectrum in a single TR, by which we can acquire the whole brain spectrum in a short time . In this study we have explored changes in brain temperature due to cerebral metabolic changes in control, mild and moderate TBI subjects.

Jiachen Zhuo, Li Jiang, Chandler Sours, Prashant Raghavan, Jerry Prince, Rao Gullapalli

Even mild TBI patients with negative CT and MRI may experience persistent post-concussive symptoms (PCS) and declined cognition more than 3 months post injury. In this prospective study of regional brain volume changes in mTBI patients, we found progressive thalamic atrophy from acute to chronic stages post injury, especially within the patient group that showed persistent PCS at 6 months. Thalamic volume atrophy also correlated with cognitive fatigue and processing speed within the same symptomatic mTBI group. Further studies on vulnerability of the thalamus may provide more insights into TBI recovery and lead to potential Therapies.

Lynn Della Grotta, Jillian Urban, Megan Johnston, Elizabeth Davenport, Mark Espeland, Youngkoo Jung, Daryl Rosenbaum, Alex Powers, Joel Stitzel, Joseph Maldjian, Christopher Whitlow

Millions of children play American football, however, youth players are largely absent from studies addressing the public health questions about safety and concussion.  Furthermore, many studies investigating effects of sports-related head impact exposure on brain structure have focused on white matter, with few evaluating the effects on gray matter (GM) structure. In this study, we combined measures of head impact biomechanics and brain MRI to investigate the effects of repetitive non-concussive exposure on gray matter volume and microstructural integrity. We demonstrate statistically significant relationships between exposure metrics and MRI measures of GM diffusion characteristics after one season of youth football.

Michael Alosco, Benjamin Rowland, Yorghos Tripodis, Hujun Liao, Alicia Chua , Brett Martin, Ofer Pasternak, Sarina Karmacharya, Johnny Jarnagin, Christine Chaisson, Robert Cantu, Martha Shenton, Richard Greenwald, Michael McClean, Neil Kowall, Ann McKee, Robert Stern, Alexander Lin

This study examined magnetic resonance spectroscopy (MRS) as a potential biomarker for chronic traumatic encephalopathy (CTE). 79 former National Football League players and 23 same-age controls completed MRS. Cumulative head impact index (CHII) estimated repetitive head impact (RHI) exposure. Principal component analysis derived clinical composites. Former NFL players had lower parietal white matter (PWM) NAA (p=0.048). Higher CHII predicted lower PWM creatine (p=0.028). Anterior cingulate gyrus (ACG) metabolites correlated with visual memory (p=0.008-0.044). ACG glutamate (p=0.032) and glutamate/glutamine (p=0.012) predicted psychomotor/executive function. Posterior cingulate gyrus myo-inositol predicted verbal memory (p=0.048). MRS may facilitate detection of RHI-related neurological conditions, including CTE.

Suk-tak Chan, Jonathan Welt, Emad Ahmadi, Eva Ratai, Jacqueline Namati, Michael Lev, Jarone Lee, Anastasia Yendiki, Benjamin Vakoc, Blair Parry, Cora Ordway, Rajiv Gupta

There is increasing evidence that neurovascular dysregulation contributes to the persistent symptoms in patients with traumatic brain injury (TBI). Damaged microvasculature may disrupt the neurovascular coupling, where the local cerebral blood flow (CBF) no longer matches the metabolic requirements of the tissue. In the present study, we found that there was a diffuse hypoperfusion at thalamus, posterior cingulate gyrus, precuneus and white matter in 2-week follow-up scan relative to the 48-hour initial and 3-month follow-up scans.  Low perfusion was sustained in both frontal and parietal cortices in 3-month follow-up scan.  Our perfusion findings in these brain regions suggest that hypoperfusion may play a role in the post-traumatic symptoms of moderate TBI.

Yukai Zou, Xianglun Mao, Ikbeom Jang, Nicole Vike, Thomas Redick, Thomas Talavage, Joseph Rispoli

Understanding how contact sports activities potentially affect the brains and cognitive abilities of adolescent athletes in both short and long-term scales is critical. Using 3 Tesla diffusion-weighted imaging (DWI) and tract-based spatial statistics, this study investigated the white matter microstructure of 13 high-school female soccer athletes over one competition season. No significant difference of DWI metrics across the season was observed. However, regression analyses showed significant effects of years of high-school experience and concussion history on the DWI metrics within corticothalamic and limbic pathways, and the abnormal changes of DWI metrics may relate to cognitive impairments.

Joong Kim, Laurena Holleran, Pashtun Shahim, David Brody

Most concussive brain injury is not readily detected in conventional MRI or standard DTI, requiring advanced imaging methodology. However, reliability of any newly developed imaging technology should be tested prior to starting full scale studies. Here we present a protocol which will enable inter-lab comparison of any advanced diffusion imaging technology with objective quantitative analysis. High spatial resolution diffusion imaging with optimized multiband pulse sequence performed on subjects twice at 1.25 mm isotropic voxel size. Post image processing including outlier exclusion and distortion correction was optimized. Brain parcellation based quantitative analyses was used to provide objective measures of reproducibility.

Sushanta Mishra, Subash Khushu, Gurudutta Gangenahalli

The inflammatory response following traumatic brain injury (TBI) is regulated by phagocytic cells, comprising resident microglia and infiltrating macrophages. The present study was to monitor the early effect of monocytes/phagocytic accumulation and further to explore its kinetics in TBI mice. Localized macrophage population was monitored using USPIO nanoparticles enhanced in vivo serial magnetic resonance imaging (MRI). Flow cytometry based gating study was performed to discriminate between resident microglia (Ly6G¯¯CD11b+CD45low) and infiltrating macrophages (Ly6G¯CD11b+CD45high). Imaging and flow cytometric analysis revealed that maximum macrophage infiltration occurs between 66-72 h post injury (42-48 h post administration of USPIO) at the site of inflammation.

Lasya Sreepada, Joshua Ladner, Huijun Liao, Benjamin Rowland, Kristin Heaton, Alexander Lin

The objective of this ¹H MRS study was to determine the neurochemical profiles of military members with mild Traumatic Brain Injury (mTBI) and compare with age-matched, healthy military controls. Analysis of metabolite concentrations in three brain regions revealed a significant global decrease in total creatine (tCr) in mTBI subjects, as well as elevated GSH in the posterior cingulate and increased Glx in both posterior white matter and anterior cingulate regions, when compared to controls. These results could identify key biomarkers of mTBI and indicate neuroinflammatory changes and impaired brain function or integrity in mTBI.

Tsang-Wei Tu, Georgios Papadakis, Zsofia Kovacs, William Reid, Dima Hammoud , Joseph Frank

The current study investigated the CEST sensitivity and specificity for simultaneous glucose (glucoCEST) and glutamate (gluCEST) detection on a phantom and a rodent brain injury. Using a median saturation power (2μT) and short saturation duration (2s), the MTRasym at 1.2, 2.1 and 2.9ppm could detect the glucose content, while the MTRasym at 3ppm could measure the glutamate in vivo. The glucoCEST results were compared in parallel to the ¹⁸F-FDG PET detecting the tissue uptake of glucose, while the gluCEST data were shown comparable to ¹⁸F-DPA PET radio-ligands binding to translocator protein (TSPO) for imaging microglial activation in the injured brain.

Suk-tak Chan, Jonathan Welt, Emad Ahmadi, Jacqueline Namati, Michael Lev, Jarone Lee, Benjamin Vakoc, Eva Ratai, Anastasia Yendiki, Blair Parry, Cora Ordway, Rajiv Gupta

There is an increasing evidence that neurovascular dysregulation contributes to the persistent symptoms in patients with traumatic brain injury (TBI). Damaged microvasculature may disrupt the neurovascular coupling, especially under physiological stress, where the local cerebral blood flow (CBF) no longer matches the metabolic requirements of the tissue.  Our findings of negative or abnormally delayed blood oxygenation level dependent (BOLD) signal changes in response to breathhold challenge can potentially be used as an imaging marker to localize subtle abnormal vascular function in individual patients with moderate TBI. The restoration of abnormally delayed BOLD responses at chronic stage suggest that such an imaging marker may be used to follow up the patients.  

Fengshan Yu, Dinesh Shukla, Christina Marion, Kryslaine Radomski, Reed Selwyn, Regina Armstrong, Bernard Dardzinski

Mild traumatic brain injury (mTBI) often involves single (s-mTBI) or repetitive (r-mTBI) head injury, which may differ in the potential for long term symptoms and chronic neurodegeneration. Non-invasive approaches that can detect damage and predict outcome are a high priority for clinical care of mTBI patients. Magnetic resonance (MR) diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) techniques can identify microstructural changes associated with Gaussian (DTI) and non-Gaussian (DKI) water diffusion properties. Mouse models of s-mTBI and r-mTBI targeting anterior brain regions (impact site at bregma) were developed for longitudinal MRI studies with corresponding neuropathology.

Alvin Silva, Yuan Le, Yuxiang Zhou, Anshuman Panda, Catherine Chong, Arvin Forghanian-Arani, Kevin Glaser , Jun Chen, Annelise Silva, Kent Nelson, Richard Ehman

As concussion, even when symptomatic, can be occult on routine imaging, there is clinical need for a more accurate diagnostic assessment.  The objective of this study was to assess the utility of brain magnetic resonance elastography (MRE), a non-invasive neuroimaging technique, to detect changes in brain stiffness in concussed patients relative to healthy controls.

Hui-Hsien Lin, Hua-Shan Liu, Ping-Huei Tsai, Fei-Ting Hsu, Chia-Feng Lu, Yu-Chieh Jill Kao, Wen-Jin Hsieh, Ho-Fang Huang, Huai-Lu Chen, Paul Blakeley, Gilbert Aaron Lee, Cheng-Yu Chen

The present study investigated whether quantitative susceptibility mapping is able to identify particular characteristics of alterations in white matter and other brain regions in patients with mild traumatic brain injury (mTBI). Our study suggests that quantitative susceptibility mapping is capable of indicating iron and myelin disturbances in white matter and thalamus for patients with mTBI.

Ferdinand Schweser, Deepa Ramasamy, Jesper Hagemeier, Barry Willer, Nicola Bertolino, Dhaval Shah, David Poulsen, John Leddy, Robert Zivadinov

This work explored the hypothesis that the activation of N-methyl-D-aspartate (NMDA)-receptors in the thalamus results in persistent calcium deposits after a sports-related concussion that can be visualized clinically with Quantitative Susceptibility Mapping at 3 Tesla. The study involved 22 retired professional contact-sports athletes and 45 controls. We found a significantly higher incidence of thalamic micro-calcifications in contact-sports athletes compared to controls, in particular in ice hockey players.

Abdullah Asiri, Mohammed Alnasser, Saied Alamri, Chantelle Reid, Marc Ruitenberg, Nyoman Kurniawan

Spinal cord injury (SCI) is a devastating damage that can result in permanent disabilities. MRI provides precise details of spinal cord post traumatic compression, which are useful for the diagnosis of the injury, surgical planning, post-surgical measurements and estimation long-term outcomes (Kramer, Freund, & Curt, 2014). In this study, 4 SCI mice were scanned at the 9.4T to acquire high-resolution images and diffusion tensor imaging at two b-values. The area of both white and gray matter were measured in several slices and compared to the pre-injury imaging. Spinal cord white and gray matters were also examined using DTI. 

Peng Sun, Rory Murphy, Paul Gamble, Ajit George, Wilson Ray, Sheng-Kwei Song

Spinal cord injury (SCI) is a significant public health problem. A major shortcoming limiting efforts to improve the treatment of SCI is the lack of quantifiable metrics on which to base clinical decisions. In current study, we have utilized diffusion basis spectrum imaging (DBSI) to more accurately differentiate and quantify axonal injury, demyelination, inflammation and edema/tissue loss. DBSI results suggest chronic SCI does result in axonal injury and edema/tissue loss at the level of the cerebral peduncle.  These results demonstrated axons may be preserved rostral to the site of injury, and may provide some insight as to why some patients respond to more recent epidural stimulation even years out from injury.

Mitchell Doughty, Michael Noseworthy, Rober Boshra, Kyle Ruiter, John Connolly

Recently there has been considerable attention directed towards the increased risk for head injuries that athletes face while participating in high impact sports.  Furthermore, there is also heightened interest in asymptomatic sub-concussive blows that possibly lead to long term neurological deficits.  The goal of this study was to investigate retired professional athletes, who played at least 4 seasons of Canadian football, using functional connectivity mapping and DTI techniques.  When compared to an age matched control population, differences were observed both in functional and structural connectivity, suggesting that even years after retiring the brain still exhibits signs of damage.

Martyn Paley, Steven Reynolds, Nurul Ismail, Mari Herigstad, Deborah Jarvis, Paul Griffiths

A wireless accelerometer has been used to measure rotation angles on a dedicated neonatal MRI system. The measured angles have been used to help correct the k-space data to reduce ghosting artifacts. No interference between the accelerometer and the MR system was observed.  Some limited improvement in ghosting was found but further work is required on the reconstruction algorithm. The device offers fast temporal resolution  (10ms) and no sequence acquisition time overhead as it is a totally independent measurement system.

Ece Ercan, Gopal Varma, Burkhard Maedler, Ivan Dimitrov, Marco Pinho, Ben Wagner, Elizabeth Davenport, Joseph Maldjian, Robert Lenkinski, Elena Vinogradov

Inhomogeneous magnetization transfer (ihMT) imaging is an enhanced magnetization transfer technique, which has been shown to produce a higher white/gray matter contrast compared to conventional MT methods. This contrast is thought to be originating from dipolar order effects in myelinated tissues. In this study we compare ihMT with myelin water imaging and diffusion tensor imaging.

Rajiv Menon, Azadeh Sharafi, Ravinder Regatte

In this study, we demonstrate the in vivo feasibility of    multicomponent 3D-T1rho relaxation mapping of  whole  brain using 3T MRI in five healthy subjects. Our preliminary results suggest that the bi-exponential model better represents the relaxation behavior in white matter and has potential to differentiate between different water compartments associated with myelin bound water (short component) and intra-extracellular water (long component).

Vesna Prckovska, Tim Peeters, David Moreno-Dominguez, Paulo Rodrigues

Diffusion MRI tractography is central to the study of complex brain circuitry since it is the only non-invasive technique capable of measuring the brain’s wiring. Data visualization gets increasingly complex as tractography is combined with morphometric results in structural connectomes, and even more so when coupled with functional information from fMRI techniques. Such complex imagery, aggregating multi-modal information, 3D meshes, and statistical maps is often visualized using research tools with complicated user interfaces (UIs) and cluttered visualizations.

BrainVis is a sophisticated, free 3D neuroimaging visualization tool with a simple UI aimed for effective exploration of neuroimaging data towards demonstrating neurobiological findings.

Jun Xie, Wei Peng, Jian Zhang, Da Chang, Ze Wang

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) have been consistently shown to be beneficial for treating various neuropsychiatrical or neuropsychological disorders, however its neural mechanisms still remain unclear. In this study, we measured the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF). The results showed the rTMS induced CBF redistribution in the default mode network, including increased rCBF in temporal cortex which was correlated with increased behavior performance, but reduced rCBF in precuneus and cerebellum.

Jean-François Cabana, Guillaume Gilbert, Nikola Stikov, Julien Cohen-Adad, Laurent Létourneau-Guillon, Dang Nguyen

We explored the utility and complementarity of different diffusion and relaxometry metrics for cortical imaging. The following metrics were assessed for correlation: mean kurtosis (MK) from diffusion kurtosis imaging, intra-cellular volume fraction (ICVF), from the NODDI model, intra-neurite volume fraction (VINT), from the multi-compartment microscopic diffusion imaging (MCMICRO) model, R1 (=1/T1), R2* (=1/T2*) and the ratio of T1w/T2w images. Some global similarities can be seen between most cortical maps, while some features that suggest complementarity between diffusion and relaxometry maps were also observed. This study emphasizes the importance of better understanding and characterising the relationship between different MRI-derived metrics.

Ute Ludwig, Anne-Kathrin Eisenbeiss, Philipp Amrein, Tabea Flügge, Johannes Maier, Katja Nelson, Jan-Bernd Hövener

High-resolution MRI of the lower jaw with an isotropic voxel size of 350 μm was performed at 3T using a 4-cm loop coil (LC) with and without an inductively coupled volume coil (ICC) enclosing the target region. Within this region, a much higher SNR was obtained and the resolution of anatomical details was strongly enhanced with the ICC. A new, custom-made holder for the LC improved the overall handling. Compared to earlier results, the scan time was reduced by 50%, now 2 minutes, to provide very high resolution MRI of 2-3 teeth.

Liam Timms, Codi Gharagouzloo, Ju Qiao, Zihang Fang, Praveen Kulkarni, Anne van De Ven, Craig Ferris

We use a technique based on positive contrast quantitative imaging of super paramagnetic iron oxide nanoparticles with optimized parameters which we have previously introduced called QUTE-CE to measure CBV across a detailed rat brain atlas. This is done for an anesthetized state and then changes in an awake hypercapnic state are additionally quantified. The former provides a baseline for future work and reflects evolutionary and developmental forces. The latter demonstrates the potential of the technique for measuring changes in CBV and provides a measure of perfusion reserve. 

Miguel Chuapoco, Ben Duffy, Hyun Lee, ManKin Choy, Jin Lee

Combining unit recording and fMRI is a powerful method that allows for interrogation of the brain at the cellular and network level. However, implanted metal recording electrodes produce susceptibility artifacts that distort MR images. Here, we fabricate single carbon-fiber electrodes and implant them into rat hippocampus and use an agarose phantom to quantify its MR distortion. These carbon-fiber electrodes record from a single unit in CA1 and distort a significantly lower volume of voxels compared to metal electrodes. These results lay the groundwork for an electrode design that can be used for single-unit recording and fMRI in same subjects. 

Mário João Fartaria , Alexis Roche, Alexandra Sorega, Kieran O'Brien, Gunnar Krueger, Bénédicte Maréchal, Pascal Sati, Daniel S. Reich, Tobias Kober, Meritxell Bach Cuadra, Cristina Granziera

Ultra-high-field Magnetic Resonance Imaging (7T MRI) has been shown to be a valuable tool to assess focal and diffuse pathology in multiple sclerosis (MS) patients, both in grey- and in white-matter. In this work, we developed and evaluated a method to automatically assess MS lesion load using magnetization-prepared two inversion-contrast rapid gradient-echo (MP2RAGE) MRI at 7T. The validation was conducted in a cohort of twenty MS patients from two research centers through a ground truth based on manual segmentations performed by a radiologist. Our single-sequence segmentation accurately detects visible white-matter and cortical lesions.

Miaomiao Wang, Xianjun Li, Chao Jin, Congcong Liu, Jianxin Guo, Hui Hao, Jian Yang

In current clinical practice, the absence of standard protocol of diffusion tensor imaging (DTI) challenges the consistency of DTI data, and thus affects the accuracy of data group analysis. This study aims to assess the inconsistency of DTI-derived fractional anisotropy (FA) based on the different clinical protocols and further make them into harmonization. Results suggest the effects of slice thickness and b-value of FA are anatomy dependent, which is more stable in white matter with packed and orientation consistent fibers. Besides, a developed polynomial fitting model was used to make FA harmonization among different DTI protocols.

Yiming Xiao, Dante De Nigris, Ian Gerard, Yuhan Ma, Donatella Tampieri, D. Louis Collins, Hassan Rivaz

Transcranial ultrasound (TCUS) can be used to diagnose and monitor a range of neurological conditions, such as Parkinson’s disease. However, reliable quantitative examination and multi-modal image analysis that involves TCUS require TCUS-MRI registration to guide the interpretation and measurement of the TCUS. We demonstrate that accurate rigid registration can be achieved through aligning gradient orientations of the 3D TCUS and an associated pseudo-TCUS constructed from the T1w MRI.  

Kotikalapudi Raviteja, Pascal Martin, Niels K Focke, Benjamin Bender

An ideal classification of brain tissue structures as segmented gray matter (GM) has been a challenge while using standard T1-weighted image. One of the important ways of addressing this issue would be to use additional information from multispectral imaging such as T2- and T2-weighted FLAIR images. We evaluated the effect of multispectral segmentation on GM segmentation using SPM12 VBM and compared it with T1-only segmentation. We found that T1-segmentation overestimates dura, meninges and vessels as GM. This problem was successfully addressed by multispectral segmentation, which should be used as a segmentation model for future VBM studies.

Shubharthi Sengupta, Francisco Fritz, Ron Hellenbrand, René Finger, Christopher Wiggins, Alard Roebroeck

We present a modular 9.4T RF coil platform that can be used for imaging slabs of tissue as large as a sagittal section of a human brain (dia. 18cm), with a thickness of up to 2cm. The 23-channel receive array was designed with a layered printed circuit approach to ensure the coils’ decoupling and proximity to the sample and with on-coil, low-noise preamplifier circuits. A 7 channel, phased transmit array capable of parallel transmission (pTx) makes homogeneous excitation of a large range of samples possible. The high homogeneous contrast-to-noise acquisitions enabled by the coil will allow high resolution anatomical imaging at 9.4T.

Daniel Schwartz, Ramon Barajas, John Grinstead, Laszlo Szidonya, Jenny Firkins, William Rooney, Edward Neuwelt

7T imaging of neurovasculature with TOF affords sub-millimeter resolution and can make it possible to visualize extremely small vessels such as the lenticulostriate arteries; however, TOF can be hampered by flow and pulsation artifacts. K-space reordering and the administration of a contrast agent can greatly reduce these artifacts while still allowing for small vessel conspicuity. We acquired gadolinium and ferumoxytol-based MRA alongside TOF in three patients and two radiologists rated vessel conspicuity and artifact. Artifacts were diminished with contrast, though there were no differences in artifact due to k-space reordering, and vessel conspicuity was high in all acquisitions. 

Sudarshan Ragunathan, James Pipe

This focus of this work was to determine the extent of RF saturation induced bias in cerebrospinal fluid flow quantification using 2D PCMRI. The velocity distribution within a flow region inherently biases the average estimate per voxel towards faster spins in that voxel. This effect was studied through variations in flip angle. The results indicated that higher flip angles would introduce more bias in the flow estimates, which could be a possible reason for the lack of consensus concerning the use of PCMRI in determining patient responsiveness to surgical interventions in NPH studies.

Cyril Ferrer, Clemens Bos, Lisanne Kok, Masami Yoneyama, Makoto Obara, Marijn van Stralen, Chrit Moonen, Lambertus Bartels

Recently, the 3D-SHINKEI (3D nerve-SHeath signal increased with INKed rest-tissue RARE Imaging) sequence was introduced for peripheral MR neurography. This method uses an improved Motion Sensitized Driven Equilibrium (iMSDE) prepulse to suppress muscle and slow flow signal, for improved visualization of peripheral nerves. Applying this method in the abdomen would provide the potential to image the celiac plexus, which is involved in various pain mechanisms, e.g. due to pancreatic cancer and other upper gastrointestinal malignancies. In this work, we show the feasibility of MRN of the celiac plexus in volunteers by using cardiac and respiratory motion-compensated 3D SHINKEI.

Aprinda Indahlastari, Aditya Kasinadhuni, Kevin Castellano, Christopher Saar, Casey Weigel, Bakir Mousa, Munish Chauhan, Thomas Mareci, Rosalind Sadleir

actual current densities applied to the brain in neuromodulation therapies. MREIT can be used to determine actual current densities delivered to the brain by measuring Bz. Here we present Bz distributions resulting from trans-temporal current injection obtained from MREIT imaging during 10 Hz TACS in a healthy human subject. Comparisons of MREIT results to MRI-derived computational models suggested that actual contact areas between electrodes and scalp may be smaller than electrode surface areas, and in-vivo tissue conductivity values, particularly skin and skull, may be different than assumed. 

Chien-Feng Huang, Chih-Hsien Tseng, Pi-Chuan Fan, Wen-Yih Tseng

To investigate whether the white matter tracts are altered in patients with tuberous sclerosis complex, we used whole-brain tract-specific analysis of diffusion spectrum imaging (DSI) data to measure the alteration of 76 major white matter tracts, and compared the property between 27 patients and 27 matched controls. As compared to the controls, patients showed significantly lower GFA in 13 tracts. The altered microstructural integrity of the white matter tracts in TSC supports the hypothesis of underlying microstructural changes in the brains of TSC.

Ryoko Yamamori, Tosiaki Miyati, Naoki Ohno, Yuki Hiramatsu, Toshiharu Kurita, Seika Miki, Akiko Sekiya, Yuri Hoshina, Toshifumi Gabata

The glymphatic system is a waste clearance pathway in brain. During sleep, the increase in the interstitial influx results in faster waste removal. Apparent diffusion coefficient (ADC) in brain significantly changed during the cardiac cycle, and this change (ΔADC) shows the degree of fluctuation in water molecules. Therefore, we analyzed fluctuation of water molecules in the brain of healthy subjects in awake and sleep states. Maximum ADC and ΔADC of the white matter increased in sleep state. Fluctuation analysis facilitates the noninvasive evaluation of the dynamic state of water movement in the brain in sleep state as a glymphatic MRI.

Nambeom Kim, Young-Don Son, Kyung-Jin Lee, Yeong-Bae Lee, Chang-Ki Kang

The thalamus acts as a gateway to higher brain centers that are involved in cognition, sleep, arousal, as well as sensory and motor information ^1–5. Additionally, changes in the thalamic subnuclei (TS) have been implicated in a number of neuropsychiatric disorders. In a postmortem study, the neuronal number as well as the total volume of the thalamus were significantly decreased in schizophrenic subjects or elevated in major depression subjects, especially in the medial dorsal nucleus ^6,7. As a result, the ability to estimate neuronal density in the thalamic subnuclei (TS) using in-vivo imaging is highly desired.

Gavin Winston, Sjoerd Vos, Jane Burdett, M Cardoso, Sebastien Ourselin, John Duncan

Hippocampal sclerosis (HS), the most common cause of refractory temporal lobe epilepsy, is associated with hippocampal volume loss and increased T2-signal. These can be identified on quantitative imaging with hippocampal volumetry and T2 relaxometry. Whilst hippocampal segmentation for volumetry has been automated, T2 relaxometry currently involves subjective manual delineation of regions-of-interest. In this work, we validate an automated technique for hippocampal T2 relaxometry and show in a group of healthy controls and patients with HS that a combination of hippocampal volume and T2 values can reliably distinguish the groups and that automated measurement is more reproducible than manual measurement.

Maryam Abaei, Sjoerd B. Vos, Derek L.G. Hill, Robin Wolz, Marios C Yiannakas, Magdalena Sokolska, Sebastien Ourselin, John Duncan, David Thomas

Multi-centre, MRI, Susceptibility Weighted imaging, Brain, Clinical Studies

Enrico De Vita, Ruth Oliver, Chris Sinclair, David Thomas, Xavier Golay, Simon Mead, John Thornton

We here demonstrate how partial volume correction by linear regression in the style originally proposed for arterial spin labelling MRI can be used to perform a simple and effective partial volume correction for Magnetisation Transfer Ratio data.

Dushyant Kumar, Hari Hariharan, Jens Fiehler, Susanne Siemonsen, Jan Sedlacik, Ravinder Reddy

Problem: The quantification accuracy of myelin water fraction mapping based on multi echo spin echo (MESE) T2 relaxometry is compromised due to high SNR requirement, along with the need to account for contributions from stimulated echo pathways.

Methods: A novel expectation-maximization post-processing method, with convergence guaranty, is proposed, which accounts for stimulated contributions intrinsically, while simultaneously improving noise robustness by utilizing spatial correlation from 3D local neighborhood.

Results & Conclusions: Results demonstrate improved quantifications as a result of the proposed algorithm.

Nico Papinutto, Rohit Bakshi, Peter Calabresi, Eduardo Caverzasi, Todd Constable, Gina Kirkish, Govind Nair, Jiwon Oh, Daniel Pelletier, Dzung Pham, Daniel Reich, William Rooney, Snehashis Roy, Daniel Schwartz, Russell Shinohara, Nancy Sicotte, William Stern, Ian Tagge, Shahamat Tauhid, Subhash Tummala, Roland Henry

Upper cervical cord area (UCCA) is strongly associated with physical disability in patients with multiple sclerosis, particularly in progressive stages of disease. Standard brain high-resolution 3D T1-weighted acquisitions that include the upper cervical cord can be used to provide estimates of UCCA.  Depending on subject positioning in the scanner, gradient non-linearity can introduce up to 10% variability in UCCA measurements from volumetric brain MPRAGE scans. In planning a study, use of 3D correction methods provided by the scanner vendors seems optimal. Alternatively, to retrospectively correct data, we propose methods based on a phantom acquisition or normalization with vertebral body diameters.

Abdullah Ishaque, Yee-Hong Yang, Sanjay Kalra

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease of the motor system with substantial disease burden in white matter. Clinical MRI studies are used only to exclude diagnoses of symptom-mimicking neurological disorders. We propose that texture analysis performed on structural MRI can provide a surrogate marker for subtle white matter changes that are observed in ALS. This study shows significant correlations between texture features from T1-weighted imaging and diffusion measures such as fractional anisotropy and mean diffusivity. These texture features also demonstrated significant differences between ALS and controls and can potentially be used clinically for diagnosis and disease monitoring.

Xiaopei Xu, Henry Mak, Kui-Kai Lau, Pak Lun Lam, Edward Hui

We aim to investigate the effect of the topology of brain microbleeds (BMBs), lobar (n = 32) versus deep/infratentorial (n = 31), on structural brain network in patients with TIA or first-time stroke. Our results demonstrated that the efficiency of the local and global networks of both BMB cohorts were lower compared to controls (n = 31), and that only the load of the patients with lobar BMBs was strongly associated with decrease in the efficiency of local and global networks independent of vascular risk factors. These findings suggested that lobar and deep BMBs likely have distinct pathophysiological underpinnings.

Ferran Prados, Manuel Jorge Cardoso, Marios Yiannakas, Baris Kanber, Hugh Kearney, Claudia Gandini Wheeler-Kignshott, Sebastien Ourselin

Multiple Sclerosis lesions can impair most automated image-processing pipelines. They can be present with different sizes, contrasts and shapes and at multiple locations across the central nervous system. Whilst lesion-filling is often a required pre-processing step in the analysis of brain MR images, its potential utility in spinal cord imaging remains unexplored. This study introduces a method for in-painting lesions in the spinal cord and demonstrates its efficacy for improving the results of spinal cord MR image analysis. 

Loredana Storelli, Elisabetta Pagani, Maria Rocca, Wim Van Hecke, Nicola De Stefano, Alex Rovira, Jaume Sastre-Garriga, Jacqueline Palace, Massimo Filippi

Aim of this study was to test two available methods (FSL-SIENAx/SIENA and Icometrix-MSmetrix) used for brain atrophy estimation on MR images of multiple sclerosis (MS) patients for a future clinical use. The accuracy and precision of these methods, as well as their main steps, were evaluated on 3D-T1 and 3DT2-FLAIR sequences of a simulated dataset, MRI of MS patients acquired at different scanners, field strengths, and on longitudinal dataset. From the comparison, SIENAx/SIENA showed a worst image registration, brain extraction and higher dependence on image acquisition quality than MSmetrix software. FSL pipelines showed better accuracy for cross-sectional and longitudinal analysis. 

Yong Jeong, Adil Javed, Nancy Arndt, Keigo Kawaji, Adam Hasse, Timothy Carroll

The development of multiple sclerosis lesions appear as different contrast mechanisms on the different MR imaging scans. In T1 weighted images, these evolve into hypointense lesions and representative of demyelination. In this study, we propose a method of quantifying T1 values using retrospective data of T1 weighted images, and apply this method to investigate potential trends of T1 changes in multiple sclerosis patients across time. We look at four patients imaged at three time points across 12 months, and find that an increase in T1 of lesions may be a trend.

Youjin Zhao, Chandan Shah, Su Lui, Qiyong Gong

An overlap of diagnosis frequently  occurs between major depression disorder (MDD) and social anxiety disorder (SAD) and few studies directly compare neuroanatomical abnormalities in the two disorders. Pure MDD patients (n = 37), pure SAD patients (n = 24) and healthy controls (n = 41) underwent T1-weighted magnetic resonance imaging (MRI). Gray matter volume and cortical thickness were compared in the three groups. The main findings of this study were that (i) MDD and SAD patients shared common neural substrates in frontal-subcortical circuits; and (ii) MDD patients manifested more widespread brain structure alterations than SAD patients.

Charley Gros, Benjamin De Leener, Allan R. Martin, Michael G. Fehlings, Virginie Callot, Nikola Stikov, Julien Cohen-Adad

Detecting the spinal cord on a large variety of MRI data is challenging but essential for the automation of quantitative analysis pipelines. For the past few years, machine learning algorithms have outperformed most unsupervised image processing methods. The present study investigates the performance of two different machine learning algorithms, Convolutional Neural Networks (CNN) and Support Vector Machine (SVM), on MRI data from different vendors, with a variety of pathology, contrast, resolution and FOV. Results suggest strong performance of the CNN approach, opening the door to application in multi-center analysis pipelines.

Lukas Goede, Birte Schmitz, Henning Pflugrad, Anita Tryc, Hannelore Barg-Hock, Jürgen Klempnauer, Karin Weissenborn, Heinrich Lanfermann, Xiao-Qi Ding

With the aim to evaluate possible brain microstructural alterations associated with calcineurin inhibitor (CNI) therapy, ninety patients after liver transplantation (OLT) treated with different doses of CNI and 32 gender- and age-adjusted healthy volunteers were studied with   quantitative MRI (qMRI).  T1, T2, T2*, Proton density (PD) and phase changes (derived from susceptibility-weighted imaging, SWI) were measured in 18 brain regions (regions of interest, ROIs). The values were compared between the groups of patients and the controls, which showed significant differences between the groups, indicating alterations of brain microstructure in patients after OLT.

Ping-Huei Tsai, Yung-Chieh Chen, Shih-Wei Chiang, Hua-Shan Liu, Ming-Chung Chou, Fei-Ting Hsu, Yu-Chieh Kao, Chia-Feng Lu, Hsiao-Wen Chung, Cheng-Yu Chen

This study allows improved localization of sensorimotor-related thalamic nuclei providing non-invasive evaluation of the microstructural changes of thalamus after iNPH, which may have a potential to contribute to early diagnosis and better prognosis prediction in the patients.

Riccardo Metere, Ahmad Kanaan, Berkin Bilgic, Torsten Schlumm, Harald Möller

Quantitative Susceptibility Mapping is an imaging technique for obtaining information of the magnetic susceptibility from phase images. If the phase information is obtained from a coil composed of multiple receive elements (coil array), the resulting images need to be combined. This step is non-trivial, and several algorithms, with different performances, have been proposed. Here we compare two different coil combination algorithms: the adaptive combine method and a recently proposed extension of ESPIRiT. For each, we compared both single subject and group-averaged QSM maps, where we observed that the results are sensitive to the method used for coil combination.

Akira YAMAMOTO, Koji FUJIMOTO, Yasutaka FUSHIMI, Tomohisa OKADA, Kei SANO, Toshiyuki TANAKA, Kaori TOGASHI

We study a heuristic modification of the NESTA algorithm for compressed sensing reconstruction of TOF-MRA images, where at each iteration the calculated k-space data are replaced with the original (acquired) data wherever the latter are available. We compared the modified method with the original method. In qualitative visual analysis, reconstructed images from the modified method were a little noisier but with better vessel signal delineation. In quantitative analysis, the modified method as compared with the original method marked higher rVBR values in lower sampling ratio, and caused no image degradation in higher sampling ratio. The modified method therefore provides a viable option in improving reconstruction of the NESTA algorithm for TOF-MRA undersampled data.

Loredana Storelli, Paolo Preziosa, Elisabetta Pagani, Vittorio Martinelli, Giancarlo Comi, Andrea Falini, Massimo Filippi, Maria Rocca

Aim of the study was to adapt and evaluate on FLAIR images a recently developed semi-automatic method for segmentation of hyperintense multiple sclerosis (MS) lesions on dual-echo (DE) PD/T2-weighted MRI. FLAIR MRI scans were obtained from 17 clinically isolated syndromes patients on a 1.5T scanner. The method was based on a region growing approach initialized by manual identification of lesions. The stop condition was formulated combining intensity and edge detection constraints. High similarity with the manual segmentation (the gold standard) was found, as well as a low misclassification of lesion voxels. Operator time required for lesion segmentation was importantly reduced.

Hsin-Yu Chen, Chia-Min Chen, Teng-Yi Huang, Tzu-Chao Chuang

In this study, we present a systematic approach to derive effective MR biomarkers of cerebral cortical thickness using machine learning methods and a large-scale database. Three neuroanatomical parcellation schemes for assessing region cortical thickness were compared. The results supported using the Desikan–Killiany atlas¹ of FreeSurfer produced robust results of age and gender predictions in normal subjects. 

Shiami Luchow, Quadrelli Scott, Jameen Arm, Oun Al-iedani, Kate Skehan, Kristen Fisher, Benjamin Schmitt, Benedicte Marechal, Saadallah Ramadan

Brain architecture has been shown to change with different disease processes and this can be quantitatively measured using automated brain segmentation methods. FreeSurfer is a validated automated brain morphometry analysis method but requires time-consuming post-processing and is computationally complex. Fully automated prototype brain morphometry post-processing is available on our scanner, which generates brain morphology data at the end of the sequence acquisition and doesn’t require manual post-processing. This study confirms that this prototype software yields brain morphology data that is highly correlated to FreeSurfer for major brain regions. Therefore, it can be used to investigate biomarkers of brain atrophy in research and clinical research arenas.  

Ferran Prados, Daniil Nikitichev, Manuel Jorge Cardoso, Tom Vercauteren, Sebastien Ourselin

The process for obtaining 3D printed models from patient-specific brain Magnetic Resonance Imaging (MRI) datasets remains tedious for non-computer scientists, despite the availability of various open-source image segmentation software and the current affordability of 3D printers. In this work, we present a web app that takes advantage of cloud computing technologies to propose a practical and straigntforward system for anyone to upload brain MRI datasets and automatically receive corresponding patient-specific 3D printable models. Using our tool requires absolutely no specific installation or configuration.

Christina Andica, Akifumi Hagiwara, Misaki Nakazawa, Masaaki Hori, Shigeki Aoki

Automated brain tissue segmentation and volumetric assessment based on the quantification of the T1 relaxation time, T2 relaxation time and the proton density (PD) have demonstrated good accuracy and reproducibility. Recently, an automated myelin volume calculation based on quantitative imaging also has been introduced. This study showed that automated brain tissue and myelin volumetry based on quantitative MR imaging with lower in-plane resolutions have good repeatability and can be obtained in short acquisition times, which is beneficial for follow-up study.

Jing Li, Zhentao Zuo, Xuewei Zhang, Jie Lu, Xiali Shao, Rong Xue, Yong Fan, Yuzhou Guan, Weihong Zhang

In this study we used the Diffusion Tensor Imaging method to assess motor pathway changes in acute ischemic stroke patients after high frequency repetitive transcranial magnetic stimulation (rTMS). We found that the excitatory rTMS applied to the ipsilesional primary motor cortex induced the contralesional cortex-cerebellar loop to facilitate motor recovery. The result is consistent with those of our former studies and gives us a clue to understand the therapeutic mechanism of rTMS for early stroke patients.

yuka oikawa, okinori murata, nobuhito sasaki, ami matsumoto, akihiro ootsu, yutaka nakamura, yukari ninomiya, makoto sasaki, kohei yamauchi

We investigated whether high-resolution images obtained using ultrahigh field MRI at 7 T can detect microcerebrovascular lesions in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) that have never been detected by conventional MRI. We prospectively examined 20 patients with SLE, including five with NPSLE, using a 7 T MRI scanner. On the high-resolution T1WIs obtained at 7 T, minute punctate/linear hyperintense lesions in subcortical and/or cortical areas were found in four (80%) NPSLE patients and one (7%) non-NPSLE patient. High-resolution T1WIs obtained at 7 T can detect minute lesions, indicating intracerebral microvascular lesions in patients with NPSLE.

Osamu Togao, Akio Hiwatashi, Makoto Obara, Koji Yamashita, Ryotaro Kamei, Hiroshi Honda

In the present study, we demonstrated the clinical utility of acceleration-selective arterial spin labeling (AccASL) MR angiography (MRA) in brain arteriovenous malformations (AVMs). AccASL-MRA significantly improved the visualization of AVM in comparison with time-of-flight (TOF)-MRA. AccASL-MRA could detect the nidus and draining veins in all patients. In particular, the detection of deep venous drainage by AccASL-MRA led to the accurate Spetzler-Martin grading. AccASL-MRA could serve as a noninvasive tool to evaluate brain AVMs without the use of contrast agents. 

Kazumasu Sasaki, Tatsushi Mutoh, Kazuhiro Nakamura, Tomoko Mutoh, Yasuko Tatewaki, Tomoyuki Yambe, Yasuyuki Taki, Tatsuya Ishikawa

Early brain injury/ischemia is a recent therapeutic target of subarachnoid hemorrhage (SAH) that contributes to triggering delayed cerebral ischemia (DCI) [1]. However, little is known about the role of cerebral blood flow (CBF) and neurobehavioral profiles at acute stage on functional outcome of the rodent model to simulate clinical severity early after SAH. The present study demonstrated the feasibility of MRI-based CBF measurements using the continuous arterial spin labeling (CASL) perfusion images for precise grading of the severity in a murine model of endovascular perforation model of SAH.

Jinhee Jang, Yoonho Nam, Song Lee, Hyun Seok Choi, So-Lyung Jung, Kook-Jin Ahn, Bum-soo Kim

A developmental venous anomaly (DVA) is a common vascular malformation, with an unusual-locating collection vein and fine venous structures draining into it. Occasionally, abnormal signal intensity is combined in draining area of DVA, which is a result of venous congestion. In this work, we explored the magnetic susceptibility of draining veins in DVAs with and without venous congestion. DVAs with venous congestion showed higher susceptibility values in collecting veins than those without venous congestion. Using 3D GRE and QSM, we could assess the oxygen metabolism of brain tissue with venous congestion. 

Paolo Bazzigaluppi, Evelyn Lake, Margaret Koletar, Rafal Janik, James Mester, Conner Adams, Peter Carlen, Bojana Stefanovic

In view of the failure of neurocentric treatments for ischemic stroke, this work examines a pleiotropic modulation of the neurogliovascular unit exerts beneficial effects in the treatment of brain stroke. Oxydative metabolism of glucose in the peri-ischemic tissue has potentially detrimental effects on tissue; in contrast, ketones’ metabolism - in light of the reduced amount of oxygen required - provides a safer alternative. We employed functional CASL, in situ electrophysiology, and biochemical analysis to show short-term benefits of early administration of β-Hydroxybutyrate to metabolically challenged brain tissue following focal ischemia.  

Chau Vu, John Wood

White matter hyperintensities are lesions in the brain that exhibit high signal intensity on T2-weighted FLAIR images. In this study, we designed a seed-based segmentation method of these lesions from T2-weighted images of 1.3mm axial resolution, utilizing the local gradient field on a breadth-first search scheme as well as level thresholding and smoothing for false-positive reduction. Additionally, since clinical MRIs are at lower resolution of 1x1x5mm, we modeled the relationship between lesion cross-sectional radius and its true volume with a cubic polynomial fit to correct for stereological bias.

Erika Orita, Tetsuro Sekine, Ryo Takagi, Yasuo Amano, Takahiro Andoh, Makoto Obara, Yoshio Matsumura, Shin-ichiro Kumita

The purpose of this study was to demonstrate the feasibility of 4D Flow MRI to monitor the change of flow dynamics between before and after extracranial-intracranial (EC-IC) bypass surgery. We enrolled 14 patients who underwent EC-IC bypass. In all, 5 patients underwent radial artery graft (RAG) bypass and 9 patients underwent superficial temporal artery (STA) bypass. All patients underwent 4D Flow MRI preoperatively and 3 weeks after surgery. We measured blood flow volume (BFV) of bilateral internal carotid artery (ICA), basilar artery (BA), and EC-IC bypass artery using 4D flow MRI. Post/pre-operative BFV ratio of contralateral ICA was statistically higher in patients with the RAG bypass group than in those with the STA bypass group (1.28±0.26 in RAG bypass group vs 0.94±0.14 in STA bypass group, p<0.01). 4D Flow MRI could assess comprehensive flow dynamics of EC-IC bypass surgery. It is feasible to clarify the change of contribution from each artery.

Kenneth Jackson, Steven Liu, Christy Jackson, Richard Buxton, David Dubowitz

We examined the CBF and CMRO2 changes that accompany menstrual migraine, and evaluated the response to sumatriptan to determine the role of serotonin in migraine pathophysiology.  Migraine is accompanied by a decline in global CBF and CMRO2 that appears to be serotonin-mediated. There is also a decline in stimulus-dependent CBF to a visual stimulus, that appears to also involve serotonin, but acts differently from the global responses. A decline in visual stimulus-dependent CMRO2 is not serotonin mediated, and appears to follow the normal variation in stimulus-dependent CMRO2 response that changes with normal menstrual cycle.

Alvaro Rojas Villabona, Francesca Benedetta Pizzini, Thomas Solbach, Giuseppe Ricciardi, Magdalena Sokolska, Christos Lemonis, Enrico De Vita, Yuriko Suzuki, Matthias JP Van Osch, Roberto Foroni, Stefania Montemezzi, David Atkinson, Michele Longhi, Elisa Ciceri, Neil Kitchen, Antonio Nicolato, Xavier Golay, Hans Rolf Jäger

This study assesses whether a combination of three Magnetic Resonance Angiography (MRA) techniques, referred to as triple-MRA, can be used as an alternative to DSA for confirmation of AVM obliteration following GKR and to characterise residual AVMs in case of incomplete response.

The follow up DSA and triple-MRA of twenty-four patients were independently reviewed by two observers regarding the presence/absence of a residual AVM. Triple-MRA consistently agreed with DSA regarding the absence or presence of residual AVMs and proved to be highly suitable for characterisation of residual AVMs. 

Bing Tian, Christopher Hess, Farshid Faraji, Megan Ballweber, David Saloner

Most of the high resolution MRI(HRMRI) intracranial vessel wall studies on intracranial aneurysm are 2D or 3D non-isotropic technique with limitation of coverage and reconstruction. We applied pre- and post- 3D isotropic T1-weighted fast-spin-echo sequence (SPACE) methods on 16 patients with 21 stable intracranial aneurysms(4 patients follow up). Our studies showed that 3D T1-weighted high resolution SPACE can be used for evaluation of the vessel wall characteristics in patients with intracranial aneurysms, as well as changes in enhancement at follow up studies. Post-contrast SPACE images provide better image quality and improved diagnostic confidence.

Tao Wu, Jiayu Sun, Zhaoyang Fan

The stroke is a common cause of death. The technique of high-resolution magnetic resonance imaging (HR-MRI) has been used to depict the vessel wall. Our study aimed to evaluate thetherapeutic efficiency of the symptomatic atherosclerotic plaque in middle cerebral artery by 3D High-resolution MRI. And we compared the imaging and clinical symptom before and after the therapy. The diagnosis of the imaging is consistent with the clinical symptom. 3D High-resolution MRI is a potential imaging technology to evaluate therapeutic efficiency of atherosclerotic plaque in middle cerebral artery.

Yunduo Li, Le He, Xiangyu Cao, Xianling Wang, Shubin Chen, Rui Li, Chun Yuan, Huijun Chen

In this study, we used black-blood (BB) MRI to investigate and classify venous wall abnormalities among PT patients, and found that venous vessel wall anomalies played an important role in PT mechanism. Arachnoidal granulations overgrowth, congenital stenosis, double-lumen, arterio-venous fistula, mastoiditis and malformation were observed in this retrospective study. In conclusion, BB imaging has the potential to provide more pathological information and guide surgical treatment of PT, which is of great clinical value.  

Yilan Xu, Chun Yuan, Zechen Zhou, Le He, Rui Li, Yuanyuan Cui, Zhuozhao Zheng, Xihai Zhao

This study investigated the correlation between intracranial and extracranial carotid artery atherosclerotic disease in symptomatic patients. We found that extracranial artery disease showed larger plaque burden than intracranial artery disease. In addition, the number of extracranial plaques was found to be associated with intracranial plaque number and maximum wall thickness (MaxWT) and the extracranial carotid MaxWT was independently associated with intracraninal artery stenosis. The association of extracranial artery plaque number and MaxWT with severity of intracranial artery disease suggests that the plaque burden measurements in extracranial carotid arteries might be effective indicators for the severity of intracranial atherosclerosis.

Luguang Chen, Qi Liu, Qian Zhan, Xuefeng Zhang, Jianping Lu

Evaluation of morphologic characterization of BA plaque (such as plaque area, stenosis rate and percent plaque burden) is significant and may guide treatment decisions in clinical setting. In this study, we employed the maximal lumen narrowing sites as the referenced sites to calculate morphologic parameters. This study aims to compare the Referenced and Self-referenced measurement method methods in assessing basilar atherosclerotic plaque employing dark blood HRMRI at 3 Tesla. The present study found Self-referenced method is more convenient and even better for evaluating BA plaque.

Takuya Urushihata, Hiroyuki Takuwa, Chie Seki, Yasuhiko Tachibana, Jeff Kershaw, Yuhei Takado, Nohuhiro Nitta, Ichio Aoki, Hiroshi Ito, Takayuki Obata

We have investigated degeneration of the nerve fibers in chronic cerebral hypoperfusion model mice using DTI. Simple t-tests indicated that there are significant differences in CBF between the control and occluded sides of the brain, but there was no significant difference for MD. However, analysis of covariance showed that MD was strongly correlated with CBF, and that there were significant differences in MD between the contra- and ipsilateral sides. The result suggests degeneration of the nerve fibers due to chronic hypoperfusion. It is also suggested that CBF-related signal changes might be important for pathological diagnosis with DTI.

Jinhao Lyu, Ning Ma, Bing Wu, Xiaoxiao Ma, Lin Ma, Zhongrong Miao, Xin Lou

Multiple post labeling delay arterial spin labeling provide dynamic perfusion information in patients with intracranial artery atherosclerostic stenosis, and is of useful to study collatera circulation. In this study, two PLD ASL was used to evaluate the severity of hypoperfusion in patients with unilateral middle cerebral artery (MCA) stenosis and we found that the severity of hypoperfusion assessed by two PLD ASL was significantly correlated with collateral circulation and associated with recurrent ischemic stroke in these patients.

BINBIN SUI, PEIYI GAO, YAN LIN, YISEN ZHANG, TIANYI QIAN, XINJIAN YANG

The purpose of this study is to investigate the application value of a 3D high-resolution fat-saturated (FS) T1 SPACE sequence for the diagnosis of intracranial vertebrobasilar dissecting aneurysm (VBDA). With sub-millimetric and nearly isotropic acquisition, the 3D T1-SPACE sequence demonstrated good sensitivity and specificity for the detection of the imaging features associated with VBDAs using a large coverage area and a thin slice thickness.

Jamie Kawadler, Christina Liossi, Chris Clark, Fenella Kirkham

Although acute vaso-occlusive pain crises are common in sickle cell disease (SCD), some patients also experience chronic daily pain. This study investigated cortical areas involved in pain processing in low-pain and high-pain groups of patients at baseline of a trial with a pain burden outcome. High-pain patients had significantly thinner cortex in the right anterior cingulate cortex, bilateral posterior cingulate cortex, bilateral precuneus and left primary motor cortex. This is the first study showing structural brain abnormalities in patients with SCD and a high pain burden; these data may provide potential biomarkers for longitudinal trials of treatment for chronic pain.

Meng-Hsin Lee, Tzu-Chao Chuang, Hsiao-Wen Chung, Jie-Yuan Li, Ping-Hong Lai

Using automated segmentation, volume of brain tissues is assessed at around one week, one month, three months, and 9 months after CO exposure.  Among all 17 patients (7 male, mean age: 42.7 yr) recruited in this prospective study, seven are diagnosed with delayed neuropsychiatric syndrome (DNS) and the other ten without.  Our results indicate that the white matter volume of all DNS positive patients shows similar trends that it first increases at 1-month follow-up and then decreases, when other GM tissues remain the same.  In addition, no volume change is observed in the group without DNS.

Jo Lee, Xiaoqing Hu, Lei Zhang, Xiaoliang Zhang, Xin Liu, Ye Li

Atherosclerosis is a major cause of ischemic stroke. In this study we build a 24-channel head coil array with a special designed coil arrangement to detect non-stenotic atherosclerotic plaques.  We compare the 24-channel head coil with Siemens 32-channel coil. For imaging test, the g-factor maps of these two coil arrays are the same, which shows that the 24-channel coil has the same capability of paralleling imaging as the 32-channel coil, and SNR maps show that at the center of the phantom which corresponds to the intracranial region of the head, the 24-channel coil is as good as 32-channel coil.

Bing Wu, Jianbo Shao, Xuehua Peng, Bing Wu, Mingmei Ge, Xinhuai Wu, Hui Lin, Zhenyu Zhou

In this study, the use use of reduced FOV CUBE is studied in comparison to full FOV CUBE as well as other common techniques. It was seen that CUBE sequences provide robust and superior image details and black blood effects, due to the advantageous 3D FSE acquisition. With only 1/4 of the FOV acquired, reduced FOV CUBE may complete the scan using half of the scan time (using twice Nex) while obtaining highly consistent results as FF CUBE. Reduced FOV CUBE may also reduce the motion related artifacts that may affect the homogeneity of the lumen area.

Sen Jia, Lei Zhang, Xiaoqing Hu, Yiu-cho Chung, Jing Cheng, Xin Liu, Hairong Zheng, Dong Liang

Three dimensional whole brain and neck vessel wall imaging of high resolution facilities the imaging of intracranial and extracranial arteries in stroke patients. However, its clinical usage is hindered by long scan time. Using a 32-channel head and neck coil system specially designed for high SNR, this work investigated the feasibility of highly accelerated parallel imaging equipped with optimally selected uniform subsampling pattern based on 3D G-factor calculated from separate calibration data and joint sparsity based denoising at acceleration factor of 6.

Dhaval Shah, Michael Dwyer, Brian Koyn, Nicola Bertolino, Cheryl Knapp, Barry Willer, John Leddy, Robert Zivadinov, Ferdinand Schweser

Previous studies using Transcranial Doppler have shown that cerebral ischemia, head trauma, and cerebral perfusion pressure are associated with an impairment of the cerebral autoregulation (CA) and alteration of perfusion. However, simulating perfusion changes and quantifying them with higher specificity repetitively has been a challenge in clinics. We propose a clinical experimental setup for an MRI-based head down tilt protocol to study the CA by quantifying perfusion. We demonstrate local perfusion change results in healthy controls and a patient.

Armelle Lokossou, Olivier Baledent, Simon Garnotel, Gwenaël Pagé, Laurent Balardy, Zofia Czosnyka, Pierre Payoux, Eric Schmidt

The neurosurgical guidelines recommend low invasive intracranial pressure (ICP) monitoring with infusion tests to detect CSF dynamics alteration. In this study, we investigate how PC-MRI could be helpful in intracranial flow investigations. Eighty-three patients suspected of active hydrocephalus underwent the conventional ICP investigations. All the patients had also the day before, a rapid and simple PC-MRI to assess their cerebral blood and CSF flows. We found that patients who presented altered CSF dynamics (observed by ICP monitoring) presented also the smallest cervical CSF oscillations in the population. PC-MRI brings easy, quick and non-invasive complementary information to investigate the craniospinal dynamic.

Shuang Xia, Chao Chai, Qingyuan Yang, Sile Hu, Tianyi Qian, E Mark Haacke, Wen Shen

In this study, we used the susceptibility-weighted imaging and mapping technique (SWIM) to investigate the effect of vessel susceptibility when evaluating the severity of cerebral infarction to develop an early prognosis of patients with middle cerebral artery thrombosis. By analyzing thrombus length, thrombus susceptibility, clot burden score, and the Admission and Discharge National Institute of Health Stroke Scale (NIHSS) scores between groups divided by the presence or absence of a deep medullary vein (DMVs) and between groups divided by the presence or absence of an asymmetrically prominent cortical vein (APCVs), we found that patients with a DMVs or APCVs were not affected by the burden factors of a thrombus. Compared to an APCV, a DMV suggests the presence of a larger cerebral infarction and is associated with an increased discharged NIHSS score, indicating a poor short-term prognosis. 

Suk-tak Chan, Karleyton Evans, Allison Tian-yue Song, Rajiv Gupta, Bruce Rosen, Aneesh Singhal, Kenneth Kwong

Ischemia within the posterior circulation has been proposed as a primary mechanism for migraine. Though, in-vivo studies have yet to fully elucidate the underpinnings of this mechanism.  In the current study, angiography via time of flight (ToF) MR was used to identify potential structural deficits within the posterior circulation and hypercapnic BOLD fMRI was used to detect functional vascular defects by quantifying cerebral vascular reactivity (CVR).   All three MoA subjects demonstrated a negative correlation in BOLD signal within the red nuclei during CO2 challenge whereas the three MA patients demonstrated CVR within the red nuclei that was similar to that of the control subjects.  ToF MR angiography images from all MoA subjects showed hypoplasia of bilateral posterior communicating arteries (PCoA) in proximity of the circle of Willis.  In contrast only one out of the three MA subjects showed PCoA hypoplasia on ToF images.  Our findings of hypoplasia of posterior communicating arteries combined with abnormal CVR responses within the red nuclei provide both structural and functional evidence for differential vascular defects in the migraine samples studied. We suggest that the identified vascular deficits to impose vulnerability in midbrain blood supply that may likely contribute to the migraine pathophysiology.

Aziz Ulug, Esin Ozturk-Isik, Ani Kicik, Emel Erdogdu, Sevim Cengiz, Dilek Arslan, Seda Buker, Ali Bayram, Cigdem Ulasoglu-Yildiz, Elif Kurt, Zeynep Tufekcioglu, Basar Bilgic, Hasmet Hanagasi, Tamer Demiralp, Hakan Gurvit

High percentage of Parkinson’s disease patients develop cognitive impairment during the course of the disease progression.  An imaging marker that can identify the patients who will develop cognitive impairment would be helpful in deciding the treatment strategy for these patients.  We have used diffusion tensor imaging to identify brain structures which can be utilized to discriminate between Parkinson’s patients with mild cognitive impairment and without cognitive deficits. 

Tejashree Takalkar, Madhura Ingalhalikar, Jitendra Saini, Pramod Pal

This work presents a paradigm for predicting changes in pathology, supporting diagnosis and providing a potential biomarker for Parkinson’s disease. This is achieved by creating a high-dimensional support vector machine (SVM) based classifier that learns the underlying pattern of pathology using numerous atlas-based regional features extracted from Diffusion Tensor Imaging (DTI) data. For the dataset of 72 controls and 73 PD patients, we achieve a 10-fold cross validation accuracy of 72.8% and a testing accuracy of 78.5%. The top discriminative features included widespread patterns of mean diffusivity changes in PD. 

Gerd Melkus, Santanu Chakraborty, Fahad Essbaiheen, David Grimes , Tiago Mestre

Different quantitative MRI techniques like Diffusion Tensor Imaging (DTI) and Quantitative Susceptibility Imaging (QSM) have been used to evaluate the substantia nigra (SN) in patients with Parkinson’s disease (PD). When multimodal MRI studies are applied to acquire several quantitative parameters the analysis of each of these datasets on an individual ROI basis can time consuming. In this study we are using a co-registration approach to a standard brain template for evaluating quantitative MR data (from DTI and QSM) in the SN of PD patients and controls.

hiroto takahashi, Yoshiyuki Watanabe, hisashi tanaka, masahito mihara, hideki mochizuki, noriyuki tomiyama

Dopaminergic neurodegeneration of the substantia nigra pars compacta (SNpc) in Parkinson's disease (PD) was evaluated quantitatively using both neuromelanin and diffusion tensor imaging. For the highly reproducible image analysis of the SNpc, an automatic region-of-interest selection method was developed with a voxel-based morphometric technique. Neuromelanin which can directly quantify dopaminergic neurodegeneration and mean diffusivity could differentiate PD patients from healthy controls and were correlated with each other. We conclude that a voxel-based evaluation using both neuromelanin and diffusion tensor imaging can reveal PD related neurodegenerative changes in the SNpc and may be a useful technique for quantitative diagnosis of PD.

Oleksii Omelchenko, Zinayida Rozhkova, Irina Karaban

Parkinson's disease (PD) in mostly presented with asymmetrical motor symptoms. Disturbed sensorimotor integration and decrease of somatosensory cortex activation was previously shown. We analyzed brain activation and connectivity during the unilateral tactile stimulation in primary and non-primary hand lateralized PD patients. We have demonstrated steady contralateral S1 activation in PD. Primary hand tactile stimulation in primary hand lateralized PD patients evokes activation of primary and associative sensory, motor and executive nodes of the cortex. Mirror neuron system was activated in primary hand stimulation in PD patients. Tactile stimuli processing evokes increased connectivity of globus pallidus, premotor, prefrontal and parietal cortex.

Dilek Arslan, Ani Kiçik, Sevim Cengiz, Emel Erdogdu, Seda Buker , Zeynep Tufekcioglu , Aziz Ulug, Basar Bilgic, Hakan Gurvit, Tamer Demiralp, Erdem Tuzun, Hasmet Hanagasi, Esin Ozturk-Isik

The purpose of this study is to investigate the cerebral perfusion correlates of microtubule-associated protein tau (MAPT) and catechol-O-methyl transferase (COMT) genotypes in Parkinson’s Disease with mild cognitive impairment (PD-MCI) and PD with normal cognition (PD-CN) using multi inversion time pulsed arterial spin labelling magnetic resonance imaging (pASL-MRI). Cerebral blood flow (CBF) and arterial blood volume (aBV) maps of patients were calculated by using general kinetic model and compared between different genotypes of PD-MCI and PD-CN. It was found that PD-MCI with H1/H1 genotype of MAPT gene had a lower cerebral perfusion than PD-CN with H1/H2 genotype. 

Virendra Mishra, Karthik Sreenivasan, Christopher Bird, Dietmar Cordes, Ryan Walsh

In vivo imaging that reliably captures the impact of the spreading pathology of Parkinson’s disease (PD), including its impact on both white and gray matter, remains elusive. In this study, we applied graph-theoretical techniques to multi-site diffusion-MRI data from a cohort of early PD-subjects in Parkinson’s Progressive Markers Initiative (PPMI) database. A disrupted topological brain organization in early PD-subjects was revealed with impaired network integration, segregation, global efficiency, and local efficiency. Furthermore, there was also rearrangement of nodes in different modules between the groups. Our study opens new avenues to understanding disease progression and severity of PD from graph-theoretical approach.

Mark Meadowcroft, Carson Purnell, Douglas Peters, Qing Yang, James Connor

This work demonstrates a decrease in R2 within the ventral-nigral region of WT-HFE mice given paraquat injections.  Furthermore, the decrease in R2 relaxation rate is not observed in the H67D-HFE mutation animals.  This is the first demonstration that HFE mutations may be associated with a preservation of cellular loss in the substantia nigra and ventral-midbrain of Parkinson’s disease model animals.

Tobias Baumeister, Sun Nee Tan, Martin McKeown

Parkinson’s Disease is not normally associated with white matter changes in clinical MRI scans. Myelin water imaging was used to probe the white matter tissue integrity of mildly affected Parkinson’s Disease patients. Partial Least Squares regression was employed to find a multivariate relation between myelin water fraction along different white matter tracts and motor performance scores. We found association between myelin water fraction and rigidity, bradykinesia and tremor scores, linking changes in white matter tissue integrity to Parkinson’s Disease severity in motor scores.

bingbing gao, bing wu, liang han, jing jing, yanwei miao

Enhanced Gradient Echo T2 Star Weighted Angiography (ESWAN) can sensitively shows iron overload in brain, especially gray matter; Diffusion Kurtosis Imaging (DKI) detects microstructure change of gray matter much better than Diffusion Tensor Imaging (DTI). PD patients has the iron overload in substantia nigra, and encephalatrophy on different levels--cortex, basal ganglia and midbrain. To emplore the relation between iron overload and microstructure change in extrapyramidal nuclei, we compared DKI and ESWAN parameters in PD and healthy control groups, and analysis the correlation between them. Found that there are some relations in substantia nigra, red nucleus and putamen in PD patients. 

XIUQIN JIA, LIN SHI, TIANYI QIAN, YING LI, DEFENG WANG, PEIPENG LIANG, KUNCHENG LI

The human brain differs significantly between different individuals, as well as between different demographics (i.e., age, gender, and race). The aim of the present study was to investigate the effectiveness of a Chinese brain template, i.e., Chinese2020, on the detection of grey matter (GM) alteration between patients with Parkinson’s disease (PD) and healthy controls (HC). The results of this study indicate that Chinese2020 was more representative of Chinese populations, which suggests that neuroimaging studies based on Chinese populations should be normalized to the Chinese brain atlas and that previous studies based on Chinese populations might need to be updated.

Miguel Carvalho, Sofia Reimão, Margherita Fabbri, Daisy Abreu, Jorge Campos, Joaquim Ferreira, Rita Nunes

This study aimed to characterize changes in Neuromelanin-sensitive MR images with Parkinson’s Disease (PD) progression. The area of high signal intensity in the substantia nigra (SN) and its contrast ratio (CR) were assessed in early and late stage PD (LSPD) patients, and in healthy individuals. The relative hippocampus and midbrain volumes were also estimated from anatomical MPRAGE scans. The SN area was found to be markedly reduced in LSPD compared to early stages of the disease and so could be a useful tool to evaluate disease progression. The decrease in relative hippocampus volume could indicate cognitive impairment, characteristic of LSPD.

Krzysztof Dzieciol, Elene Iordanishvili, Zaheer Abbas, Michael Winterdahl, Adjmal Nahimi, Nadim Shah

Parkinson's disease patients were investigated in order to reveal changes inside region-of-interest – substantia nigra. 31 volunteers were scanned using a well-established, quantitative free water mapping protocol. The region-of-interest is too small to obtain reliable segmentation for region-based analysis. Therefore, statistical, voxel-wise analysis of registered quantitative maps was performed. It revealed a decrease in the metrics (free water content, T1, T2* and combination of all three) in the vicinity of substantia nigra. We conclude that the reduction in total free water content could be due to a disruption of the deep grey matter integrity. 

Na-Young Shin, Injoong Kim, Yunjin Bak, Phil Hyu Lee, Seung-Koo Lee, Soo Mee Lim

Degenerative change in the nucleus basalis of Meynert, a group of cholinergic neurons in the substantia innominata (SI) of the basal forebrain, begins in the early stages of Parkinson disease (PD) and is known to be significantly correlated with cognitive performance. We found decreased resting state functional connectivity (rsFC) in bilateral frontal areas using bilateral SI mask as a seed and significant correlation between decreased rsFC and shorter disease duration before mild cognitive impairment was diagnosed in patients with Parkinson’s disease. Therefore, our results support that cholinergic deficit plays an important role in the acceleration of cognitive decline and conversion to PD dementia.

Karthik Sreenivasan, Virendra Mishra, Zhengshi Yang, Xiaowei Zhuang, Sarah Banks, Dietmar Cordes, Ryan R Walsh, Karthik Sreenivasan

Earlier studies using fMRI have shown the existence of a modular structure for different brain networks. However, no information exist about hierarchical modular structure of functional connectivity networks in patients with Parkinson’s disease(PD). Using percolation analysis, we found a shift in the hierarchical modular structure of functional connectivity networks in patients with PD.  A shift in the modules in caudal-rostral direction in the PD group of motorically affected patients, alongside rearrangement of connector hubs and provincial hubs in PD patients was observed. Potential application of network properties observed here, as predictors of subsequent disease progression is currently being investigated.

Patrícia Paulino, Sofia Reimão, Leonor Guedes, Miguel Carvalho, Daisy Abreu, Jorge Campos, Joaquim Ferreira, Rita Nunes

Previous studies in idiopathic Parkinson’s disease (iPD) have shown a reduction in the substantia nigra (SN) area hyperintense in Neuromelanin-sensitive MR images (NM-MRI). However, a few genetic mutations have been associated to PD. In this study we compared images obtained in iPD and in patients with LRRK2 or GBA mutations. Images were also acquired in control subjects. The area and contrast-ratio of SN in NM-MRI and the relative midbrain volumes were evaluated. There were no significant differences in volumes, but the SN area in NM-MRI accurately differentiated LRRK2 PD patients from controls. No differences were found between PD groups.

Brigida Ranieri, Ilaria Rosa, Davide Di Censo, Angelo Galante, Eugenio Scarnati, Tiziana Marilena Florio, Marcello Alecci

We established the correlation between behaviour and functional structures in an early stage of 6-OHDA PD rat model. Behavioural data reveal that receptor sensitization develops few days after dopaminergic injury. The apomorphine-induced amplification of the motor asymmetry over time is paired to striatal shrinkage and alteration of the GM/WM area in the ipsilateral striatum, as revealed by immunohistology and ex-vivo high-resolution MRI analysis.

Jianli Wang, Thyagarajan Subramanian, Qing Yang

The primary olfactory cortex (POC) responds to both odor-smelling and sniffing. It is not known if there are deficits in the sniffing-related or odor-related functional activities in the POC of early-stage Parkinson’s disease (PD). Here we report significant PD-related deficit in the odor-related POC activation, while the sniffing-related activation was not significantly affected. These results suggest that olfactory deficits in early-stage PD are mainly due to the breakdown of the bottom-up mechanism. In addition, our finding of a negative correlation between the UPDRS-3 score and the odor-related POC activation suggests a surrogate marker for the clinical severity in early-stage PD.

Virendra Mishra, Dietmar Cordes, Ryan Walsh

In vivo imaging that reliably captures the impact of the spreading pathology of Parkinson’s disease (PD), including its impact on both white and gray matter, remains elusive. In this study, we performed skeleton-wise analysis of multi-site DTI data from a cohort of early PD-subjects in Parkinson’s Progressive Markers Initiative (PPMI) database. Tract-based-spatial-statistics analysis revealed three clusters mainly located in corticospinal tract, and superior frontal gyrus that had a lower AxD in early PD-subjects suggesting DTI measures can be used to differentiate controls and early PD, and can be further exploited to understand its role in disease progression and severity. 

Silvina Horovitz, Liang Li, Sule Tinaz, Mark Hallett

We modified a parcellation method to map the motor, limbic and associative territories within the subthalamic nucleus (STN).  We further evaluated whether a remapping of the STN connectivity exists in Parkinson’s disease (PD) patients. Resting-state fMRI data were analyzed using independent component analysis and general linear model. In both groups, the motor area was identified in the posterior zone, while the limbic zone was more anteriorly located. The motor connections were altered in the PD patients. Our approach could be used for functional parcellations and for remapping of functional connectivity due to disease in brain areas with heterogeneous connectivity patterns.

Ehsan Adeli, Guorong Wu, Min-Jeong Kim, Dinggang Shen

Parkinson's disease (PD) is a common neurodegenerative disorder, which progresses slowly and affects the quality of life dramatically. In this paper, we use the T1 MRI and DTI data from the PPMI study to analyze the effect of each modality through investigating the brain regions, and determine which modality can be a better marker at diagnosing the disease. For this purpose, we propose a joint feature selection and max-margin classification framework, in which we select features that best benefit the classification scheme. Our results show that the brain structural connectivity studies using DTI leads to better results.

Roxana Burciu, Edward Ofori, Derek Archer, Samuel Wu, Ofer Pasternak, Michael Okun, David Vaillancourt

We used a bi-tensor model to calculate free-water (FW) in the substantia nigra (SN) from diffusion MRI scans obtained from the Parkinson’s Progression Marker Initiative (PPMI) database with the goal of monitoring disease progression over 1 year and 4 years in Parkinson’s disease (PD). Results confirm previous single-site findings by showing an increase in FW in the posterior SN over 1 year in a large multi-site study, and extend the literature by showing that FW levels in this structure continue to increase over 4 years.

Xiaofei Hu, Yuchao Jiang, Xiaoyue Zhou, Cheng Luo, Jian Wang

In the current study, combined functional connectivity density (FCD) and seed-based FC analyses were performed to fully characterize the abnormal brain networks in the two subtypes. Our findings obtained using a combination of FCD and seed-based FC analyses provide consistent evidence for that the network disorganization of the brains in the two PD subtypes were different.We also found that the FCD provided good discrimination between the AR and TD patients. These findings have important implications for understanding the neural substrates that underlie these disparate manifestations of PD.

Xiaofei Hu, Xiaoyue Zhou, Panli Zuo, Jian Wang

We try to find out the longitudinal volume change of different hippocampal subfields in patients with PD with and without cognitive decline using magnetic resonance image (MRI). Our result shows that there is cross-sectional and longitudinal regional atrophy of specific hippocampal subfields in PD, which becomes more severe and is further extended to the bilateral CA2-3 and CA4-DG subfields in patients with cognitive decline. These results corroborate neuropathological findings and add novel information about the involvement of the hippocampus in the cognitive dysfunction of PD.

Sevim Cengiz, Ani Kicik, Emel Erdogdu, Dilek Arslan, Seda Buker, Zeynep Tufekcioglu, Aziz Ulug, Basar Bilgic, Hakan Gurvit, Tamer Demiralp, Erdem Tuzun, Hasmet Hanagasi, Esin Ozturk-Isik

Microtubule-associated protein tau (MAPT) and catechol-O-methyltransferase (COMT) genotypes have been associated with cognitive impairment in Parkinson’s disease (PD). The aim of this study is to compare MR spectroscopic imaging findings between cognitively normal PD (PD-CN) or mild cognitively impaired PD (PD-MCI) patients with different MAPT and COMT genotypes at 3T.  We observed a higher Ins/Cr in cerebral white matter of PD-MCI with MAPT H1/H2 genotype than PD-CN with MAPT H1/H1 genotype and a higher Cho/Cr in thalamus of PD-MCI with COMT Met/Met genotype and PD-CN with COMT Val/Val or Val/Met genotype than PD-CN with COMT Met/Met genotype. 

Sean Sethi, Shawn Kisch, Kiarash Ghassaban, Saifeng Liu, Miller Fawaz, Ali Rajput, Alex Rajput, Paul Babyn, Peter Szkup, E. Haacke

Iron deposition in the brain has been implicated in neurodegenerative diseases like Parkinson’s Disease. We used quantitative susceptibility mapping to evaluate iron content in the substantia nigra and red nucleus in 18 patients with idiopathic Parkinson’s Disease (IPD). Susceptibility was calculated for whole structure and a thresholded high-iron region (RII) and compared with controls. We found that global and RII mean susceptibility higher in the substantia nigra compared with normals, and that the slope of RII susceptibility vs age is higher in IPD compared to normals which may suggest an increased rate of iron deposition at disease onset. 

Marta Correia, James Rowe

In this study we combined machine learning with MRI for the differential diagnosis of three movement disorders: Parkinson’s disease (PD), progressive supranuclear palsy (PSP) and degenerative corticobasal syndrome (CBS). We compared the performance of such approaches when using T1-weighted and diffusion MRI, as well as different methods for feature extraction. Our results suggest that such methods could be used in the future to aid the differential diagnosis of PSP, CBS and PD, in conjunction with clinical assessment, with diffusion MRI data providing the most promising results. 

Dietmar Cordes, Muhammad Kaleem, Xiaowei Zhuang, Karthik Sreenivasan, Zhengshi Yang, Virendra Mishra, Ryan Walsh

In this project, amplitudes of low-frequency fluctuations in resting-state fMRI data of subjects with Parkinson’s disease (PD) are studied and compared with matched normal controls. Empirical Mode Decomposition (EMD) is used to decompose the natural occurring frequency bands of major networks important in PD. The novelty of our approach lies in the data-adaptive decomposition of fMRI data using EMD, and identification of resting-state networks based on amplitude characteristics of intrinsic modes. 

Jung-Sen Hsiao, Sung-han Lin, Chih-Chien Tsai, Chiung-Mei Chen, Jiun-Jie Wang

Huntington’s Disease (HD) is a neurodegenerative disease would result in atrophy in basal ganglia especially in caudate nucleus and putamen in the early stage of the disease. The cortical parcellation algorithm was applied to evaluate the cortical involvement in the patients with HD by using diffusion MRI and compared with voxel based morphometry. The mean diffusivity is feasible in the brain of patients with HD, which is more sensitive than the morphometric changes. Therefore mean diffusivity could be a potential image based biomarker for monitoring HD progression.

Katherine Koenig, Jian Lin, Mark Lowe, Stephen Rao, Mourany Lyla, Deborah Harrington, Jane Paulson for the PREDICT-HD investigators of HSG, Sally Durgerian

This study investigates intrinsic functional connectivity of the dorsal caudate in prodromal Huntington’s disease participants. We find that connectivity to the left caudate increases as estimated time to a manifest diagnosis decreases, and that stronger connectivity between the right middle frontal gyrus and left caudate is predictive of future cognitive decline.

Enrico De Vita, Sarah Gregory, Lauren Byrne, Filipe Rodrigues, Eileanoir Johnson, Tarek Yousry, David Thomas, John Thornton, Edward Wild

Iron levels in the basal ganglia in Huntington’s disease (HD) have been previously investigated at  3T with MRI using magnetic field correlation imaging, T2*, quantitative susceptibility mapping (QSM), as well as T2 relaxometry mostly at lower fields of 1.5T or less. We performed T2 mapping at 3T in a group of pre-HD (n=10) and HD patients (n=11) to investigate its association with Disease Burden Score and structural measures (caudate volume) of disease load. We found significant correlations between T2 and disease progression measures in nucleus accumbens, putamen and pallidum.

Jessica Steventon, Hannah Furby, James Ralph, Peter O'Callaghan, Anne Rosser, Monica Busse, Kevin Murphy

 Exercise is potentially therapeutic via vascular adaptations (angiogenesis, improved cerebral perfusion and metabolism) however the underlying dynamics are not fully understood. In Huntington´s disease (HD), where the therapeutic potential of exercise is being explored, cerebral vasculature alterations have been reported.

Here we used arterial spin labelling to examine the acute effect of aerobic exercise on the cerebrovasculature in HD patients. We show that genetic disease load is related to both baseline cerebral blood flow (CBF) and the exercise-induced change in CBF.

Eric Fang*, Chu Ning Ann*, Bénédicte Maréchal, Shawn Yan Zhi Tan, Julian Gan , Huihua Li, Eng King Tan , Ling Ling Chan

Postural instability gait disorder (PIGD) subtype in Parkinson's disease (PD) is a major cause of morbidity. We quantified whole-brain structural changes in PIGD patients, PD patients and controls using an automated volume-based morphometry algorithm that is objective and reproducible. Compared to PD and controls, PIGD subgroup demonstrated a significant decrease in brain and globus pallidus volume, as well as grey matter content in both caudate and thalamus; but an increase in ventricular size, abnormal white matter volume and relative caudate size. MRI findings also correlate with gait imbalance severity in PIGD, suggesting a mechanism of temporal differences in segmental volume loss. 

Jessica Steventon, Hannah Furby, James Ralph, Anne Rosser, Kevin Murphy

Motion artefacts pose significant problems for the acquisition and analysis of MRI data. In movement disorders, severe motion-related artefacts can result in data being discarded as non-usable. It is not known to what degree clinical movement symptoms can predict in-scanner motion artefacts, and thus, whether researchers can target recruitment for MRI studies based on clinical presentation.   Here we investigate whether movement severity in Huntington’s disease, a neurodegenerative movement disorder, can predict in-scanner motion artefacts in arterial spin labelling data. We find that motion magnitude and variability is not more pronounced in Huntington’s disease and not related to symptom severity.

Gina Kirkish, Anisha Keshavan, Nancy Byl, William Stern, Stacy Hatcher, Tracy Luks, Roland Henry

A paradigm was developed to evaluate neural pathophysiology of gait and turning in individuals with Parkinson’s disease (PD) using fMRI. BOLD signal change of imagined walking and turning was compared to resting state activation in PD patients and controls. Subjects performed physical examinations including the Timed Up and Go (TUG) task, ten-meter walk and a timed 360-degree turn to assess motor performance. Brain activity was compared between groups and to motor performance. This study concluded that a neural correlate of the TUG task exists in BOLD signal change in the premotor and primary motor area when imagining-turning compared to imagining-walking.

Alexey Dimov, Yihao Yao, Ilhami Kovanlikaya, Pascal Spincemaille, Jonathan Rasouli, Brian Kopell, Yi Wang

Deep brain stimulation is a surgical procedure routinely used in the treatment of advanced stages of Parkinson disease. DBS involves implanting of stimulating electrodes inside the patient’s brain, with STN most commonly being the target brain structure. Treatment efficiency and absence of negative side effects is strongly dependent on precision of electrode placement; therefore, high requirements are imposed on preoperative patient imaging for proper identification of anatomy of interest. Histochemical studies suggest that iron (one of the major contrast contributors in QSM) is densely and heterogeneously distributed in STN. Furthermore, it is hypothesized that distribution of iron might be related to functional subdivisions in STN. Thus, DBS surgery planning might benefit from more precise calculation of susceptibility distribution, which would allow observe and characterize gradients in iron concentration in in vivo patient data potentially leading to minimization of non-motor side effects. Accordingly, we develop a high resolution QSM protocol for DBS presurgical MRI protocol.

Hirotoshi Maruyama, Yasuhiro Fujiwara, Tsukasa Sakemoto

Magnetic resonance neurography (MRN) of the brachial plexus using a 3D turbo spin echo (TSE) sequence with short-term inversion recovery (STIR) reduces the effect of fat suppression at 3.0 T. In addition, the signal intensity of the brachial plexus is influenced by changing the effective echo time (TEeff). Therefore, we optimized the fat suppression technique and TEeff so that the 3D TSE sequence, using a combination of STIR with SPIR and an optimal TEeff (from170 ms to 293 ms), achieved better visualization of the brachial plexus without residual fat.

Kojiro Ono, Yasuhiro Oikawa, Takayuki Sakai, Hirofumi Watanabe, Akira Shirayama, Takumi Okubo, Atsushi Senoo

The STIR Low-RFA PROPELLER method is a combination of STIR (Short-TI Inversion Recovery) suppressing fat signal homogenously and low refocus flip angle (Low-RFA) PROPELLER for flow signal reduction. Furthermore, the PROPELLER is able to reduce ghost generated by flow and motion, and to maintain high resolution by averaging of k-space. Consequently, the STIR Low-RFA PROPELLER method will be expected to produce clear brachial plexus imaging which is not affected by motion. In this study, we demonstrate that this new scheme (STIR Low-RFA PROPELLER) is superior to the conventional method (T2 weighted IDEAL) in the depiction of brachial plexus.

Chunyao Wang, Xiao Han, Wen Jiang, Xiaodong Ma, Hua Guo, Le He, Huijun Chen

Cervical Spondylotic Myelopathy (CSM) is a major cause of spinal cord dysfunction. However, the relationship between the degree of stenosis, tissue degeneration and sensorimotor dysfunction have not been well understood.In this study, 3 healthy volunteers and 17 CSM patients with different postoperative recovery degree were involved. We investigate the perfusion of spinal cord using MR DSC technique. The results showed a significant correlation between CBV and the postoperative severity of symptom (Japanese Orthopaedic Association score), which indicate that MR DSC perfusion of spinal cord could be an imaging biomarker to evaluate and understand CSM.

Allan R. Martin, Benjamin De Leener, Julien Cohen-Adad, David W. Cadotte, Jefferson R. Wilson, Lindsay Tetreault, Stefan F. Lange, Aria Nouri, Adrian Crawley, David J. Mikulis, Howard Ginsberg, Michael G. Fehlings

Degenerative cervical myelopathy (DCM) is a common cause of disability, but mild patients are often managed non-operatively and monitored for deterioration. Popular clinical assessment tools are insensitive to detect subtle disease progression. In this study, we employ multi-parametric spinal cord MRI to monitor 15 DCM patients for progression over a 1-year period, in addition to a comprehensive battery of clinical assessments. The MRI results detected progressive tissue injury in 6/7 patients with definite clinical progression and 5 additional patients (4 of which had borderline clinical progression). These MRI assessments are now being incorporated into clinical practice to inform surgical decision-making.

Marco Battiston, Torben Schneider, Ferran Prados, Francesco Grussu, Marios Yiannakas, Sebastien Ourselin, Claudia Gandini Wheeler-Kingshott, Rebecca Samson

The T₁ relaxation time is a fundamental quantitative Magnetic Resonance parameter widely used to characterize healthy and pathological tissue. However, quantitative T₁ mapping in the human spinal cord (SC) has been limited to date, mainly due to its small size and sensitivity to artefacts. Here we assess the reproducibility of a time efficient (<5min) SC protocol for Inversion Recovery T₁ mapping, which is considered the gold-standard method for T₁ estimation. Scan-rescan experiments were performed in a cohort of 4 healthy subjects. High reproducibility (whole cord intraclass correlation=0.94) of T₁estimates was found, with whole cord intra-subject coefficient-of-variation<15% for all subjects.

Robert Harrigan, Bennett Landman, Seth Smith

Quantitative magnetization transfer (qMT) sampling schemes typically attempt uniform sampling of the MT z-spectrum but this may not be optimal for PSR estimation of the human spinal cord in vivo. We utilize Monté Carlo simulations of fitting synthetic qMT data to produce an optimal sampling scheme of the MT z-spectrum. This sampling scheme is evaluated in a healthy control and compared to current best practices where we see superior PSR estimation with our optimized sampling scheme. 

Masaaki Hori, Issei Fukunaga, Ryo Ueda, Kouhei Kamiya, Yuichi Suzuki, Katsutoshi Murata, Tomohiro Takamura , Nozomi Hamasaki, Ryusuke Irie, Kanako Kumamaru, Michimasa Suzuki, Shigeki Aoki

We investigated MR fiber g-ratio, AVF and MVF in evaluation of microstructural changes in the spinal cord in patients with cervical spondylotic myelopathy, with using atlas-based analysis by spinal cord tool box. 19 patients and 5 normal controls were included. MT-sat and NODDI data were collected at 3T MRI. The right side of fasciculus cuneatus and bilateral lateral corticospinal tracts (LSCT) of AVF were significant lower (P=0.014, 0.017, 0.014, one-way ANOVA with Scheffé’s post-hoc test) and the left LSCT of MVF was significant higher (P=0.037) in the affected side spinal cord, compared with normal controls.

Martina Liechti, Marios Yiannakas, Nuttakarn Budtarad, Ahmed Toosy, Xixi Yang, Ferran Prados, David Miller, Henry Houlden, Claudia Gandini Wheeler-Kingshott, Jalesh Panicker

Magnetic resonance imaging (MRI)-derived tissue-specific measures of neuronal loss and demyelination were assessed at the lumbosacral level of the spinal cord (SC) in relation to neurological dysfunction. Acquisition of grey and white matter measures for the lumbosacral SC proved feasible, and were sensitive to detect tissue-specific changes in two neurological disorders commonly associated with lumbosacral cord involvement: Multiple system atrophy and Multiple sclerosis. This preliminary study demonstrates the utility of this cutting edge MRI acquisition method to detect pathological changes in the lumbosacral SC, and is a first step towards establishing new MRI biomarkers for these patient groups.

Ute Ludwig, Tabea Flügge, Katja Nelson, Fabian Duttenhöfer, Ralf Kohal, Dominik von Elverfeldt, Jan-Bernd Hövener

The purpose of the study was to demonstrate the feasibility and evaluate the limitations of high-resolution MRI of ceramic implants in vivo. One healthy volunteer was subjected to high-resolution MRI before and after two zirconia dental implants were placed in the lower right jaw. Both implants were clearly depicted as signal voids, and no artifacts were observed using a turbo spin echo sequence. In conclusion, high-resolution in-vivo MRI of ceramic implants with an isotropic voxel size of (600 μm)³ is feasible within 5 minutes scan time.

Jo Lee, Xiaoqing Hu, Lei Zhang, Xiaoliang Zhang, Xin Liu, Ye Li

In this study, we build an optimized 32 channel head-neck coil array to improve the weak SNR of area behind cervical spine from the previous designed neck-coil array. Two of the original eight neck coils is place to the area near scruff with a new structure. Comparing the optimized 32-channel head neck coil with the previous: imaging test has improved 63% higher than the previous coil array. For g-factor measurement, optimized neck coil array is the same as the previous one. The results indicate that the optimized coil array is better for neck imaging.

Yu-Chia Cheng, Yi-Jui Liu, Yi-Hsiung Lee, Hing-Chiu Chang, Hui-Chu Chiu, Ta-Wei Chiu, Kang Hsu, Hsian-He Hsu, Chun-Jung Juan

The parotid gland function is evaluated by gustatory stimulation using scintigraphy in clinic. Due to the saliva secretion of parotid, it is supposed to measure the water component of parotid gland using PD MRI instead of scintigraphy. Normally the drop magnitude and recover rate of signal-time curve after gustatory stimulation was used to evaluate the function of parotid gland. For more physiology and quantitative parameters of characteristics of signal-time curve, we developed a mathematical model for drainage and refill of a toilet tank to quantify the parotid gland function in this study.

Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Kohsuke Kudo

We assessed the utility of diffusion parameters obtained by multiple fitting models for the determination of the presence of the residual tumor after the curative chemoradiation in patients with head and neck squamous cell carcinoma (HNSCC). The result of the current study revealed the center of the Gaussian distribution of diffusion coefficient (D_s) in the statistical diffusion model and diffusion heterogeneity parameter in the stretched exponential model were respectively indicated as an independent predictor for the determination of the presence of residual tumor. This result will be useful information for the daily clinical follow-up in patients with HNSCC.

Keiya Hirata, Yuuichi Murasaki, Chihiro Watari, Tatsunori Kuroda, Nanako Miyamoto, Saeko Tomida, Tomokazu Oku, Shigeo Miyazaki, Masahiro Kawashima, Ichirou Toyota, Mariko Doai, Hisao Tonami

 A flow-sensitive black blood (FSBB) sequence is usually used for 3D-T2*WI imaging. In an FSBB sequence, the vascular signal is suppressed by the effect of motion-probin- gradient (MPG) pulses. If this advantageous signal suppression is used, then 'contrast-enhanced volume black blood imaging' could be obtained.

Rosario Lopez Gonzalez, Sin Yee Foo, William Holmes, William Stewart, George Welch, Barrie Condon, Keith Muir, Kirsten Forbes

Atherosclerotic carotid plaque morphology and plaque composition may identify unstable or vulnerable plaque that defines higher risk. The aim of this study is to evaluate the ability to identify all major carotid plaque components in in-vivo 3T, ex-vivo 7T MRI and correlation with histology.

Mami Iima, Akira Yamamoto, Ichiro Tateya, Morimasa Kitamura, Atsushi Suehiro, Yo Kishimoto, Kaori Togashi

The association of diffusion parameters in patients with head and neck cancers was investigated using the different diffusion times. Although ADCo significantly decreased (p<0.05) and fIVIM increased (p<0.05) using 51ms compared to 19.1ms, there was no difference of K values. The effects of the diffusion time on IVIM and non-Gaussian diffusion parameters are not clear in head and neck cancers. Our preliminary study requires further validation with shorter diffusion time or better SNR.

Yumi Koizumi, Masaru Sonoda, Tsutomu Inaoka, Hideki Nagatomo

The purpose of this study is to assess image qualities of MPR images depending on imaging planes of Cube to determine the optimal imaging plane in the cervical spine. The differences of FWHMs in frequency and phase encoding directions of the transverse, sagittal, coronal source images were compared and those encoding directions on the transverse, sagittal, coronal MPR images were compared. MRI of Volunteers image qualities were recorded by assessing sharpness of the vertebral body, spinal cord, and nerve roots on the images. To provide better image qualities in cervical spine MRI using Cube, transverse planes should be selected.

Mahdi Alizadeh, Chris Conklin, Devon Middleton, Sona Saksena, Laura Krisa, Scott Faro, MJ Mulcahey, Feroze Mohamed

In this study we have investigated on evaluating the ability of texture analysis of routine conventional pediatric spinal cord MRI to characterize the changes of diseased or injured spinal cord. 

Shiho Isoshima, Masayuki Maeda, Katsuhiro Inoue, Ryohei Nakayama, Shinichi Takase, Tsunehiro Yamahata, Hajime Sakuma

Quantitative assessment of carotid plaque burden is required to monitor the effects of treatments for carotid atherosclerosis. Cervical carotid plaque volume in 13 patients with carotid artery stenosis was measured and evaluated using manual and automated software methods for 3D T1 black-blood MRI. Measurement reproducibility was better using the automated method than that using the manual method. The automated software developed for the measurement of carotid plaque volume was feasible and reliable and could significantly reduce the measurement time. This method appears to be of great value in clinical settings.

Judy Alper, Rafael O'Halloran, Bradley Delman, Raj Shrivastava, Priti Balchandani

Trigeminal neuralgia (TN) is a debilitating condition characterized by severe facial pain. The pathophysiology of TN is not well understood and conventional clinical imaging often fails to identify the anatomical source of pain. In this study, we perform high-resolution 7T structural, vascular and diffusion-weighted MRI to visualize the trigeminal nerve region in three TN patients and three controls. We found that 7T-MRI provided improved visualization of nerve abnormalities compared to clinical scans. We also found greater nerve asymmetry in TN patients compared to controls. Multi-modal 7T-MRI could enhance our understanding of TN etiology and provide improved clinical outcomes for TN.

Rodolfo Gatto, Weiguo Li, Manish Amin, Luis Colon-Perez, Jin Gao, Thomas Mareci, Scott Brady, Gerardo Morfini, Richard Magin

Amyotrophic lateral Sclerosis (ALS) is characterized by progressive degeneration of spinal cord motor neurons. To address the role of axonal pathology in ALS, we generated a YFP,G93A-SOD1 reporter mice. Our goal in this study is to evaluate if presymptomatic alterations in MRI water diffusion in the YFP,G93A-SOD1 mice are related to alterations in axonal connectivity by histological methods. Results showed presymptomatic changes in diffusion parameters are associated to specific structural changes in axonal population. The use of this new animal model will help us to understand the structural basis of changes in water diffusion in ALS.

Dushyant Kumar, Hari Hariharan, Jens Fiehler, Susanne Siemonsen, Jan Sedlacik, Ravinder Reddy

Problem: The clinical utility of myelin water fraction (MWF) mapping based on multi-echo-spin-echo (MESE) T2-relaxometry is prohibitively slow (~90-120 minutes for acquisition matrix 128x128x50; TR 3s). MWF-values from T2-prep based approach and mcDESPOT (Multicomponent-driven-equilibrium-single-pulse-observation-of-T1-and-T2) matches poorly with MESE based quantification.

Methods: We compare GRASE (Gradient-and-Spin-Echo) based MWF quantifications against those from MESE and compare our algorithm against current state of the art. 3D non-selective GRASE, MESE were optimized. Implemented post-processing method utilizes spatial correlations in 3D local neighborhoods to improve noise stability, while simultaneously accounting for stimulated echo contributions.

Results & Conclusions: Results demonstrate good consistency between both sequences.

Peter Adany, Douglas Denney, In-Young Choi, Erica Sherry, Abbey Hughes, Sharon Lynch, Phil Lee

Thalamic pathology has been linked to long-term accumulation of disability and cognitive impairment in MS. However, assessment of thalamic volume is highly challenging for automatic as well as manual segmentation techniques. The use of multiple image contrasts may improve segmentation quality. We investigated correlations of thalamic volume and cognitive performance in MS. We evaluated automatic segmentation and our new semi-manual segmentation using T1 and proton-density MRI. Results based on FreeSurfer segmentation failed to yield correlations of thalamic volume with cognitive performance in MS patients. Using semi-manual segmentation, significant correlations were found between cognitive impairment and regional thalamic atrophy in MS.

Weiwei Chen, Yan Zhang, Ketao Mu, Susan Gauthier, Yi Wang, Wenzhen Zhu

Differentiation MS lesions from ischemic demyelinating lesions is important because of their totally different treatment strategies. Our results suggested that the increased susceptibility of demyelinating lesions, the presence of QSM-ring lesions and the central vein in the lesions helped to differentiate MS lesions from ischemic demyelinating lesions. Thus, QSM provided the underling iron-related pathogenesis of MS lesions, which enable to differentiate MS lesions from ischemic demyelinating lesions. 

Elise Van Obberghen, Samira Mchinda, Arnaud le Troter, Valentin Prevost, Patrick Viout, Elisabeth Soulier, Maxime Guye, Gopal Varma, David Alsop, Jean-Philippe Ranjeva, Jean Pelletier, Olivier Girard, Guillaume Duhamel

The present study was aimed at evaluating the potential of ihMT (inhomogeneous Magnetization transfer) contrast in characterizing the severity of MS disease, and investigating possible correlations between ihMT and the clinical disability score.

Wenzhe Xue, Christine Zwart, Joseph Hoxworth, Dean Wingerchuk, J. Ross Mitchell

This paper presents a new method to segment MS lesions in multi-spectral MRI exams. Our approach leverages the speed of a GPU level set algorithm and a new data term to perform multiple segmentations of brain white matter in each exam. Differences between these segmentations allow us to estimate the distribution of MS lesions. We evaluated our method on BrainWeb and MS Lesion Segmentation Challenge 2008 data. It achieved results comparable to, or better than, two top performing algorithms. The average time required by our algorithm for Challenge08 data was 20.8 seconds.

Anna Combes, Katrina McMullen, Irene Vavasour, Emmanuelle Lapointe, Robert Carruthers, David Li, Gareth Barker, Anthony Traboulsee, Shannon Kolind

Investigations into thalamus pathology, a known predictor of disease progression and cognitive impairment in multiple sclerosis, have yielded inconsistent results in neuromyelitis optica spectrum disorder. We found significant thalamic atrophy, but normal multicomponent relaxometry parameters in patients compared to healthy controls, providing further evidence that despite volume loss, microstructural alterations are likely subtle. Associations between MRI metrics (thalamic volume and T₁ relaxation time, linked with changes in water content) and performance on two measures of information processing speed support the hypothesis that damage to the thalamus may be involved in cognitive impairment in this population.

Adnan Alahmadi, Rebecca Samson, Matteo Pardini, Egidio D'Angelo, Karl Friston, Ahmed Toosy, Claudia Gandini Wheeler-Kingshott

This study investigates whether it is possible to characterise different resting state fMRI (rsfMRI) networks connected to the cytoarchitectonic subdivisions of Brodmann area 4 (BA4) and how these networks behave in the presence of multiple sclerosis (MS). We showed that each sub-region identifies different rsfMRI networks, with the BA4p network including more associative and higher order functional areas whereas the BA4a network includes more force-related and motor areas. In MS, functional connectivity to the right hemisphere was lost and was positively correlated with the 9-HPT, suggesting a maladaptive mechanism rather than a compensatory mechanism.    

Adil Maarouf, Soraya Gherib, Patrick Viout, Maxime Guye, Bertrand Audoin, Jean Pelletier, Jean-Philippe Ranjeva, Wafaa Zaaraoui

Assessment of neuro-degenerative process in multiple sclerosis using sodium MRI. A study in a population of 135 subjects at different disability and disease duration

Tim Sprenger, Michael Czisch, Brice Fernandez, Ines Eidner, Jonathan Sperl, Axel Haase, Frank Weber, Marion Menzel, Philipp Sämann

A systematic comparison of diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) regarding the sensitivity to non-pathological white matter in multiple sclerosis is presented. We found first indications for a higher sensitivity of DKI compared with DTI in the normal appearing white matter compartment.

Gloria Castellazzi, Laëtitia Debernard, Tracy Melzer, John Dalrymple-Alford, Egidio D'angelo, David Miller, Deborah Mason, Claudia Gandini Wheeler-Kingshott

In this work we examined functional connectivity (FC) changes within and between the resting state networks (RSNs) caused by Relapsing Remitting Multiple Sclerosis (RRMS) in two cohorts showing mild disability but different disease duration. Our results demonstrate widespread functional alterations in both short and long duration RRMS groups (MS1 and MS2). The MS1 group showed more severe FC alterations compared to the MS2 group. Overall, these results suggest that there may be pathophysiological differences in RRMS groups with different disease durations. Longitudinal studies would be needed to investigate whether FC findings are able to predict the future course.

Bénédicte Maréchal, Alexis Roche, Tobias Kober, Wadie Ben Hassen, Alain Créange, Jérome Hodel, Pierre Brugières

We investigate the potential of a technique to automatize quantification of neuronal damage from T1-weighted MR scans in multiple sclerosis patients. T1 hypointense component measures in the deep nuclei are derived from 40 MPRAGE scans (21 relapsing-remitting MS and 19 age-matched controls) through combined brain tissue classification and atlas-based segmentation algorithms. Our analysis shows that these automated measures are significantly lower in the thalamus and putamen of MS patients, which is in line with previously reported loss of structure in these regions.

Jian Lin, Pallab Bhattacharyya, Ken Sakaie, Robert Fox, Mark Lowe

In a 2 year longitudinal fingolimod study, we investigated the evolution of white matter integrity in the brain of relapsing-remitting multiple sclerosis (RRMS) patients under fingolimod treatment. Based on dMRI metrics from HARDI scans and statistical analysis, we found that MS patients experience a continued decline in white matter integrity during the first year of treatment with fingolimod with stabilization during the second year. Without a control group, it is unclear if these trends reflect on the impact of a treatment on disease progression.
 

Sudhanya Chatterjee, Olivier Commowick, Simon Warfield, Christian Barillot

Clinical trends and Pathogenetic ways of onset and progression of Multiple Sclerosis (MS) in patients suggest that MS is a highly heterogeneous disease. MS is predominantly a White Matter (WM) disease, which is mainly composed of myelinated axons and neuroglia type cells. Demyelination and axonal loss characterize the condition of MS in a patient. However, they follow varying trends in patients. In this work, we propose a method in which T2 relaxometry data is used to obtain a quantitative brain tissue microstructure information. This information is then studied to check its corroborations with pathogenetic understanding of MS in literature.

You Jung Lee, Seoung-Eun Kim, John Rose, Eun-Ju Kim, Karen Salzman, Bradley Katz, Eun-Kee Jeong

To understand the underlying physical and pathological meaning of optic-nerve in optic-neuritis(ON), diffusion-tensor imaging (DTI) and the corresponding Monte-Carlo Simulation (MCS) were conducted. DTI studies of four healthy subjects and seven ON patients with MS were performed and analyzed by home-built software. The measured DTI indices allowed us to monitor pathological changes such as inflammation in ON or demyelination. To investigate the clinical meanings of changes in diffusion parameters, MCS of water diffusion in optic nerve was performed.

Richard Watts, Andrew Solomon, Kristen Koeller, Joshua Nickerson

A new technique combining surface-based cortical myelin maps with Z-score methodology is developed to identify foci of cortical demyelination in patients with multiple sclerosis. The technique is found to discriminate (p=0.002) patients with MS (n=19) from patients with migraine (n=10), who often present with similar symptoms and white matter imaging findings. Regions of unusually low myelin content may correspond to lesions visible on the source T1-weighted and FLAIR images, but in other cases may be occult on either individual scan. The technique is clinically applicable, requiring only 3D T1 and FLAIR acquisitions that are already the standard of care in clinical neuroimaging.

Ken Sakaie, Mark Lowe, Daniel Ontaneda

In situ imaging is a valuable context for validation of imaging measures against histology. This contribution describes optimization of diffusion MRI for NODDI in in situ imaging of a multiple sclerosis patient. The results are expected to facilitate validation of advanced diffusion MRI and other tissue microstructure meausrements.

Sanuji Gajamange, David Raffelt, Thijs Dhollander, Elaine Lui, Annie Shelton, Owen White, Trevor Kilpatrick, Alan Connelly , Joanne Fielding , Scott Kolbe

Axonal degeneration is a key pathological driver of disability in multiple sclerosis (MS). Treatments aiming to reduce or reverse axonal degeneration in MS require sensitive and specific markers. Here we explore putative fibre-specific markers of axonal degeneration based on diffusion-weighted MRI metrics – fibre density and fibre bundle cross-section. MS patients with optic neuritis were compared to control subjects. We identified significant reductions to both fibre density and cross-section in the visual pathways of patients. These results indicate the pathological specificity of fibre density and cross-section measures in MS.

Jon Cleary, Amanda Ng, Camille Shanahan, Yasmin Blunck, Myrte Strik, Brad Moffat, Trevor Kilpatrick, Roger Ordidge, Scott Kolbe

Multiple sclerosis (MS) is typically characterised by hyperintense T2 white matter lesions. However, the quantity and location of these may not correlate to a patient’s functional state or impending disease progression. Quantitative susceptibility mapping (QSM) is an emerging biomarker associated with tissue iron concentration and regions of demyelination in white matter. This pilot study examined both clinical and MRI parameter relationships to the QSM value over a number of brain regions in patients with mild (EDSS =or<2) relapsing and remitting MS. 

Fernanda Rueda, Thomas Doring, Eduardo Figueiredo, Soniza Alvez Leon, Roberto Domingues, Emerson Gasparetto, Romeu Domingues

In synthetic MRI, the recently developed multi delay multi–echo fast spin echo sequence (MDME) with posterior mathematical fitting provide multiple image contrasts in a single sequence acquisition and lead to potential acquisition time reductions. In this study, both, a synthetic MRI and conventional post contrast acquisition protocol for the evaluation of patients with Multiple Sclerosis were compared. Significant acquisition time reduction were achieved with synthetic MRI without neglecting lesion count capabilities

David Rudko, Josefina Maranzano, Douglas Arnold, Sridar Narayanan

Cortical pathology may be a substrate of worsening clinical symptoms in MS patients. However, the rate at which cortical pathology develops and the brain locations affected are not well known. The goal of this study was to evaluate longitudinal, age-related reductions in cortical surface magnetization transfer ratio (csMTR) of MS patients. Such reductions may be sensitive to sub-pial demyelination occurring over time.

Frederique Boonstra, Grace Florescu, Scott Kolbe, Chris Steward, Andrew Evans, Helmut Butzkueven, Peter Mitchell, Anneke Van Der Walt

This study aims to determine the correlation between clinical tremor severity in Multiple Sclerosis (MS) and the cerebello-thalamic pathway. We found a decrease in volume of the ipsilateral Superior Cerebellar Peduncle and contralateral Thalamus. These regions of volume loss correlate with predicted neuro-anatomy indicating that the cerebello-thalamic pathway is a neural correlate of tremor severity in MS. This finding aids to a better understanding of pathogenesis and development of treatments for tremor in MS.

Yihao Yao, Yi Wang

QSM and DWI are sensitive to changes in MS lesions at various ages. We found chronic MS lesions had higher relative susceptibilities and lower relative ADC values as compared to new enhanced lesions. Combining QSM and ADC measurements could differentiate each two subtypes in four subtypes of lesions (nodular/shell enhanced lesions, rim+/- lesions). The pattern of QSM and ADC findings suggests that shell enhanced lesions have more demyelination than nodular enhanced lesions and rim- lesions. Combining QSM and ADC measurements might be a better way to differentiate MS lesions at various ages and provide more information of micro-changes of lesion.

Paola Valsasina, Maria Rocca, Fiammetta Pirro, Elisabetta Pagani, Alessandro Meani, Massimiliano Copetti, Filippo Martinelli Boneschi, Vittorio Martinelli, Giancarlo Comi, Andrea Falini, Massimo Filippi

Aim of this study was to identify the MRI predictors of medium-term disability and cognitive impairment accrual in patients with the main clinical phenotypes of multiple sclerosis (MS). Results indicated that clinical disability and cognitive impairment at follow-up were predicted by measures of structural and microstructural damage, as well as by resting state functional connectivity measures. Preserved white matter integrity predicted clinical improvement. Grey matter involvement played a critical role in MS-related clinical worsening and evolution to a more severe disease phenotype.

René Schranzer, Alexander Rauscher, Evelin Haimburger, Kristian Bredies, Gernot Reishofer, Günther Grabner

The reduction of noise is of high value for FLAIR² images because the multiplication of FLAIR and T2 images will always result in an image with a reduced Signal-to-noise-ratio. Here different filter methods, like Gaussian, Wiener and Total Generalized Variation were used to demonstrate noise reduction. The drawback of noise reduction is a blurring effect of anatomical structures. In this study we demonstrate that TGV filtering has certain advantages compared to Wiener and Gaussian techniques in research and clinical applications.

Pascal Sati, Sunil Patil, Souheil Inati, Govind Nair, Gunnar Krueger, Daniel Reich

The central vein sign (CVS) detected by magnetic resonance imaging (MRI) may aid with the diagnosis of multiple sclerosis (MS).  The ability to detect central veins in the brain at any magnetic field strengths would open the pathway for future large-scale research studies, and potentially routine clinical use, of the CVS for MS diagnosis. In this study, a fast high-isotropic-resolution, whole-brain T₂^*-weighted segmented echo-planar-imaging acquisition was implemented at 1.5T, 3T and 7T. Central veins inside multiple sclerosis lesions were detected at all three different field strengths.

Scott Kolbe, Sanuji Gajamange, Jon Cleary, Trevor Kilpatrick

Here we report a novel haemodynamic signal using BOLD-weighted fMRI that is restricted to the internal cerebral veins and identifiable in all subjects assessed to date. This signal is oscillatory with peak power at 0.054 Hz. In early MS patients, venous power was diminished compared to controls. Venous power was inversely correlated with T2 lesion volume but not brain atrophy. These results indicate that neuroinflammation is associated with altered venous haemodynamics that could be attributable to venous structural damage previously reported in MS. This novel venous signal should also be investigated more broadly in cerebrovascular disease.

Parinaz Massoumzadeh, Wint (Arthur) Aung, Amber Salter, Safa Najmi, Jenny Wang, Tiffany Lin, Allysa Lui, Emily Egbert, Tammie Benzinger, Soe Mar

MS is a progressive disorder in which demyelination, axonal degeneration, and inflammation contribute to disease pathogenesis. ADEM is classically an acute, monophasic demyelinating disease in which axonal damage is present but minimal.  About 20 percent of ADEM cases can have relapses and are diagnosed with MS later, posing a diagnostic dilemma at initial presentation.  In this study, we investigate the role of directional diffusivity DTI as a MR biomarker to differentiate and predict Acute Disseminated Encephalomyelitis (ADEM) from Multiple Sclerosis (MS) in pediatric patients.

Elizabeth Powell, Thalis Charalambous, Ferran Prados, Carmen Tur, Daniel Altmann, Declan Chard, Sebastien Ourselin, Ahmed Toosy, Jonathan Clayden, Claudia Wheeler-Kingshott

Graph theoretical network properties, while successful in exploring topological features of entire brain networks, have limited sensitivity to localized disease effects. This work explores the role of node strength as an objective way to characterize disease. Differences in the default mode network (DMN) between a cohort of relapsing-remitting multiple sclerosis (RRMS) patients and healthy controls (HC) have been explored using standard graph metrics (e.g. efficiency) and node strength. No differences in graph metrics were observed between the groups; however several key regions of the DMN had a significantly reduced strength in RRMS than HC (5% significance level).

Lukasz Kalkowski, Izabela Malysz-Cymborska, Dominika Golubczyk, Miroslaw Janowski, Piotr Holak, Kamila Milewska, Zbigniew Adamiak, Joanna Wojtkiewicz, Wojciech Maksymowicz, Dorota Kedziorek, Piotr Walczak

Modeling of multiple sclerosis is typically performed in rodents; however, due to several limitations large animal models are needed to improve clinical relevance. In this study we utilized MRI-guided convection enhanced delivery of gliotoxins (ethidium bromide and lysolecithin) to induce focal demyelination within corona radiata in pigs. 

Jie Wen, Dmitriy Yablonskiy, Anne Cross

The limbic system plays an important role in the emotion- and memory-related brain functions. In this study, we measured R2* and the volumes of the key elements of the limbic system and used them to detect abnormalities in the limbic system in multiple sclerosis (MS). The results showed significant differences between Secondary Progressive MS (SPMS) and healthy group. R2* of amygdala, thalamus, insula, lateral orbitofrontal and isthmus cingulate significantly correlate with clinical cognitive tests in female SPMS. Our results also showed that R2*-defined tissue alterations in the hippocampus and entorhinal cortex could identify depression behavior in MS patients.

Mehran Azimbagirad, Antonio dos Santos, Luiz Murta Junior

Brain tissue volume estimation based on MRI is crucial to several diseases such as multiple sclerosis (MS). The Images from different scanners with dissimilar magnetic fields have disparities in resolution, Signal to Noise Ratio, contrast, among others. In order to convert volume estimations from different scanners, we suggest and evaluated two methods. The dataset to validate the methods was selected from 14 years follow up study of 72 MS patients with 1.5 and 3.0 Tesla acquisitions. The quantitative study of tissue volume progress is possible using these two methods.

Francesca Bagnato, Assunta Dal-Bianco, Richard Dortch, Idan Kantor, Bailey Lyttle, Siddharama Pawate, Lydia Mckeithan, Bailey Box, Simon Hemetner, Hans Lassmann, Brain Welch, Seth Smith

7T imaging and the commensurate T1-lenghtening have the potential to increase lesion sensitivity at the expense of their specificity in patients with multiple sclerosis. In our work we demonstrate that (1) T1-hypontense lesions detected on T1-w MPRAGE reflect both remyelinated and chronic demyelinated lesions as measured by histology and that (2) associations between black hole lesion load and measures of physical and cognitive disability are weak. At 7T, the increased sensitivity to lesion penalizes the T1-w MPRAGE specificity to areas with higher water content and tissue destruction seen at lower field strength.

Ajit George, Peng Sun, Anne Cross, Xiaojie Wang, Carlos Pérez-Torres, Sheng-Kwei Song

In this study, we demonstrate diffusion basis spectrum imaging (DBSI) is able to detect, differentiate and quantify different coexisting pathologies, particularly axonal loss and demyelination within autopsied multiple sclerosis human brain specimens. We correlated the DBSI derived maps with quantitative histology maps generated by means of color based segmentation. DBSI-derived fiber fraction was seen to correlate with Bielschowsky’s silver stain for axonal integrity, and the DBSI-derived radial diffusivity negatively correlated with Luxol Fast Blue-Periodic Acid-Schiff (LFB-PAS) stain for myelin integrity. 

Lisa Eunyoung Lee, Anna Combes, Jillian Chan, Robert Carruthers, Jacqueline Palace, Lucy Matthews, Anthony Traboulsee, Shannon Kolind

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are demyelinating central nervous system disorders that may present with some overlapping clinical symptoms but differ pathophysiologically. We used tissue-specific quantitative measures, produced by mcDESPOT, to characterize tissue pathology in MS and NMOSD groups compared to healthy controls. We observed decreased myelin water fraction, increased T2 of intra/extracellular water, increased cerebrospinal volume fraction, and increased myelin water residence time in the brainstem and corpus callosum of MS and NMOSD subjects, compared to controls. These sensitive advanced MRI measures could provide an improved understanding of MS and NMOSD pathogenesis. 

Ningnannan Zhang, Zhang Zhang, Tianyi Qian, Wen Qin, Qiuhui Wang, Chunshui Yu

This study reports the preliminary application of high-resolution diffusion tensor imaging (DTI) using readout segmentation of long variable echo trains (RESOLVE) sequence for spinal cord imaging in patients with demyelinating conditions. Patients with clinical isolated syndrome (CIS) and multiple sclerosis (MS) were recruited in order to investigate image evidences in early stages and the progression of the disease. The results of DTI analyses demonstrate that MS is characterized by diffuse axonal compensation in the spinal cord.

Shrushrita Sharma, Yunyan Zhang

Measurement of tissue coherency has been largely relying on advanced MRI. Here we presented a coherency-assessing method based on standard T2-weighted MRI. Postmortem brain samples from multiple sclerosis (MS) patients were used to validate our method. It was based on Fourier transform power spectrum, from which dominant tissue-aligning directions and angular entropy were calculated. Tissue coherency in histology was quantified using structure tensor analysis. We found that both MRI and histology coherency differentiated MS lesions from NAWM, and that MRI coherency correlated significantly with histological results. These findings suggest the potential of T2-weighted MRI in characterizing advanced tissue pathology

You Jung Lee, Bijaya Thapa, Nabraj Sapkota, Eun-Ju Kim, Lubdha Shah, Eun-Kee Jeong, John Rose

Diffusion tensor imaging (DTI) is considered as a biomarker to quantitatively evaluate the pathology in the cervical spinal cord (CSC) in MS patients. However, DTI parameters, including axial and radial diffusivities, and fractional anisotropy (FA), provides signal behavior of the water diffusion at a specific diffusion weighting. Using a ultra-high B DWI on a CSC specimen and Monte-Carlo Simulation indicate that we can learn much more insights about the CSC pathology by analyzing the signal-b curve at b > 4000 s/mm2. In this presentation, we will show unique signal behaviors of UHB-rDWI in acute and chronic legions in MS CSC. 

Peng Sun, Ajit George, Robert Naismith, Sheng-Kwei Song, Anne Cross

Axon injury and loss, demyelination, and inflammation are the primary pathologies in multiple sclerosis (MS). However, the roles that these individual pathological processes play in MS progression are still ill defined. To investigate whole brain white matter (WM) changes, diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) were analyzed on Tract Based Spatial Statistics (TBSS) skeleton template. Both whole brain voxel-based group analysis and regional correlation analysis at the corpus callosum supported that DBSI metrics were able to quantitatively assess the white matter alterations. DBSI could be useful for quantitatively monitoring MS patient treatment and assessing neuroprotective therapies.

Marianne Drabek, Diane Reckziegel, Cottam William, Xingfeng Li, Nadia Frowd, Hamza Alshuft, Brigitte Scammell, Thomas Kurien, Dorothee Auer

Chronic pain is a major problem for society and further studies are needed to understand pain-related developments. In particular, controversy exists over the pattern of pain-related structural changes in the brain. The current morphometric study addresses inconsistencies through a large sample of chronic osteoarthritis knee pain patients and healthy volunteers scanned at a single-site, allowing to differentiate sex effects which are usually ignored. We found significantly decreased gray matter density in pain patients in several brain regions, amongst which the left planum temporale which was driven by the female subjects and has not been mentioned in relation to pain before. 

Baohong Wen, Dandan Zheng, Li Zheng, Jingliang Cheng

This study used voxel-based morphometry method to examine gray matter volume alterations related to impulsive personality traits in obese individuals relative to controls. 62 adolescents completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were firstly analyzed at the whole brain range. The relationship of regional GM volumes with UPPS-P scores were examined in selective regions of interest. This study demonstrated that sensation seeking behavior in obese people negatively correlate with GM volumes of amygdala, OFC, hippocampus, and insula indicate high sensitivity to food cues in adult obesity that link to certain alternations of the brain structure. 

Samantha Ma, Jin Kyu Gahm, Lirong Yan, Yelong Shen, Xingfeng Shao, Yonggang Shi, Danny JJ Wang

Cerebral small vessel disease frequently affects the lenticulostriate arteries, resulting in silent strokes which contribute to progressive cognitive impairment in elderly persons. Recent studies have demonstrated the ability of MRI to non-invasively image these small arteries at 7T; however, ultrahigh magnetic field is not commonly available in clinical practice. This preliminary study evaluates the feasibility of visualizing and characterizing the lenticulostriate arteries using whole-brain and ZOOMit 3D T1-weighted turbo spin-echo at 3T. 

Jon Cleary, Peter Yoo, Brad Moffat, Robert Williams, Susie Kerby, Ryan Jefferies, Simon Murray, Andrew Tan, Ben Loveridge, Amanda Ng, Sonal Josan, Leah Leighton, Varsha Pilbrow, Junhua Xiao, Jenny Hayes, Roger Ordidge

Grasping human head and neck anatomy can be challenging for students, scientists and health professionals in medical disciplines. Ultra-high field, 7T MRI can create high-resolution images with multiple contrasts, revealing structural detail not easily apparent in dissection specimens. While widely exploited in clinical and scientific studies, its use has been limited so far in creating tools for medical education. We present a multi-modal combination of ex-vivo MRI and CT to create a high-quality head and neck anatomy resource to enhance cadaveric cross-sectional anatomy teaching.

Ian Tagge, Lois Colgin, Rebecca Ducore, Betsy Ferguson, Steven Kohama, Jodi McBride, Martha Neuringer, Sam Peterson, Scott Wong, Robert Zweig, Anne Lewis

Neuronal ceroid lipofuscinosis (NCL; also known as Batten Disease) is a fatal neurodegenerative disorder that typically presents in childhood. Currently, no treatments are known that can halt or reverse the effects of NCL. A naturally occurring form of NCL analogous to late infantile-onset NCL in humans has been identified in a population of Japanese macaques (JMs). MRI examinations revealed marked cerebellar degeneration in NCL animals >4y/o (~14y/o equivalent human age) compared with controls, which is strikingly similar to human disease. This novel JM model presents a new opportunity for characterizing disease progression, identifying biomarkers, and pre-clinical therapeutic testing.

LIN SHI, PEIPENG LIANG, YISHAN LUO, KAI LIU, Vincent CT MOK, Winnie CW CHU, DEFENG WANG, KUNCHENG LI

Understanding how brain changes over the lifetime provides the basis for new insights into neurophysiology and neuropathology. In this study, we carried out a pseudo-longitudinal study based on large-scale cross-sectional high-resolution brain MR data atlas Chinese2020 to model the brain morphological changes in Han Chinese adulthood. Our results found some novel age-related neuroanatomical changes in a standardized brain space via temporal-spatial statistical brain templates.

TzyShyuan Ng, Vincent Chin-Hung Chen, Dah-Cherng Yeh, Ren-Horng Wang, Jun-Cheng Weng

Cancer-related trauma after chemotherapy has been widely reported by breast cancer. The previous study consistently showed lower gray and white matter volume and density in patients treated with chemotherapy. The aim of this study was to find out the early effect in both brain volume and shape in the chemotherapy-treated breast cancer patients compared to healthy controls using voxel-based morphometry (VBM) and vertex-wise shape analyses, respectively. Our results showed significant changes in the brain structural volume and shape, particularly in the putamen and hippocampus.

Yu Zhang, Yun-fei ZHA, Liang LI, Lei HU, Hui Lin, Bing Wu

To explore the potential for high-resolution MR imaging using IDEAL FSE-T2WI as compared to FSE-T2WI in the assessment of the basilar artery wall. High-resolution FSE(A/P), FSE(R/L) and IDEAL FSE(A/P) T2W images were acquired from basilar artery of 30 patients using a 3.0T MRI scanner.The threeimage sets were evaluated for overall image quality and graded using a 4-point Likert scale.IDEAL FSE-T2WI (A/P) scores is higher than FSE-T2WI (A/P) and FSE-T2WI (R/L).FSE-T2WI (A/P), FSE-T2WI (R/L) andIDEAL FSE-T2WI (A/P) difference with statistical significance,respectively.IDEAL FSE-T2WI images showed improved image quality compared to FSE-T2WI technique at 3T.

Kevin Lee, Sara Bohnert, Cory Vair, Ying Wu, John Mikler, Jeff Dunn

Soman is a chemical warfare nerve agent that is categorized as a weapon of mass destruction. Nerve agents are potent irreversible inhibitors of acetylcholinesterase and exposure can be extremely lethal. At a sub-lethal dose, our understanding of the neurological effect is limited. To understand the soman associated physiological changes, MRI was used to quantify the cerebral blood flow after a convulsive dose of soman. 

Fei Cong, Jiawei Wang, Zhangyan Yang, Yan Zhuo, Bo Wang, Yuqing Zhang, Lin Chen

The pedunculopontine nucleus (PPN), as a potential Deep brain stimulation (DBS) target for the patients to improve gait and posture. Until now, only a few results of the location of PPN has been published. In this study, 7T ultra-high field MR system and high resolution MP2RAGE sequence were used to locate the PPN by a direct view, manually measurement and fiber tracking method were used to verify the results. The results showed a clear and accurate location of PPN. 

Yunwen Shao, Zhengjun Li, Marta Vidorreta, Sudipto Dolui, Nick Bryan, John Detre

Variability in regional relative cerebral blood flow (CBF) from resting-state arterial spin labeling (ASL) MRI data obtained in a large (N=436) cohort were examined using spatial Independent Components Analysis (ICA). Some spatial patterns of intersubject CBF variability resembled known resting-state functional networks, and were largely reproducible across split samples. Network relative CBF fluctuation across subjects was about 14%.

Sohae Chung, Els Fieremans, Joseph Rath, Yvonne Lui

The relationship between performance on working memory tasks of increasing difficulty and white matter (WM) microstructure assessed by diffusion kurtosis imaging (DKI) is investigated in a healthy adult population. We demonstrate that higher mean kurtosis (MK) and radial kurtosis (RK) correlate with performance on working memory tasks, particularly in frontal WM, an area responsible for executive function, suggesting better working memory performance with higher tissue complexity in frontal WM. Improving our understanding of these associations will help determine the biological underpinning of pathologies affecting cognition, as well as potentially informing and monitoring interventions such as cognitive rehabilitation.

Xuntao Yin, Zhichao Li, Guangyao Jiang, Xiaoyue Zhou, Jian Wang

We examined morphological and diffusion changes of the corpus callosum (CC) in the same group of amputees for the first time. The thickness, area and diffusion tensor imaging (DTI) parameters were used to investigate the CC. Diffusion alteration in the region II of the CC was found in amputees compared with health controls. These changes suggest that fibers connecting bilateral premotor and supplementary motor areas are damaged. The alteration is only reflected in DTI parameters rather than morphological characteristics, indicating that DTI is more sensitive to detect the brain reorgnization following amputation. 

Marco Gruwel, Peter Latta, Anna Wojna-Pelczar, Stefan Wolfsberger, Boguslaw Tomanek

Aneurysm clips are used to stop or prevent an aneurysm from bleeding. MRI is an ideal technique to diagnose aneurysms. Unfortunately, treatment assessment by MRI after surgical placement of an aneurysm clip is complicated due to the presence of the metal clip. The clip's high magnetic susceptibility causes severe, orientation dependent, variations in the local magnetic field. Often this results in pronounced MR image distortions including signal voids. The study presented here shows how ultra-short and zero echo time experiments could be used to minimize these artifacts.
 

Rita Gil, Daniel Nunes, Noam Shemesh

Organotypic slices are excellent controlled systems for investigating neural activity without many of the confounds introduced by in-vivo conditions. Here we describe a new setup that allows imaging of a living slice inside a MRI scanner while being stimulated with optogenetics which induces neuronal activity in pre-targeted neurons. This setup allows the survival of slices for at least three hours, without requiring new artificial CSF (aCSF) to be flushed. This property is highly advantageous for avoiding artifacts related with bubbles, motion or variation of shims during extended acquisitions. 

Alan Seifert, Marco Hefti, Mary Fowkes, Junqian Xu

Zero echo time imaging (ZTE) of deuterium oxide (D₂O)-exchanged unfixed white matter is a proven method for measurement of myelin density. In this work, we perform D₂O-exchanged ZTE measurements on human spinal cord tissue before and after formalin fixation to assess whether fixation, which cross-links proteins, impacts the measured myelin density.  A segment of human spinal cord was obtained at autopsy, subjected to D₂O-exchanged ZTE myelin density measurement, chemically fixed using formalin, and re-measured.  Signal intensity was 31.36%, normalized to a reference, before fixation, and 31.44% after fixation.  These similar measurements support this method’s accuracy in fixed tissue.

Robin Lüddecke, Julia Forstenpointner, Janne Giertmühlen, Ralf Baron, Olav Jansen, Thomas Lindner

Wearing a necktie is mandatory in several professions. However, the constant restriction of the veins (and potentially arteries) might lead to adverse side-effects, which could already be visualized regarding intraocular pressure. In this study, the effects of a tight necktie are investigated using Arterial Spin Labeling to measure brain perfusion and venous phase-contrast angiography to show changes in venous flow velocities.

Ravi Prakash Reddy Nanga, David Roalf, Kevin D'Aquilla, Catherine DeBrosse, Puneet Bagga, Neill Wilson, Dushyant Kumar, Ari Borthakur, Mark Elliott, Damodar Reddy, Hari Hariharan, Neill Epperson, Ravinder Reddy

In this study we employed the single-slice 2D glutamateCEST (GluCEST) MRI to measure the reproducibility as well as changes in GluCEST with age in healthy human brains. GluCEST MRI appears to be a promising technique that can characterize neuronal changes in normal aging.

Dong Zhang, Changzheng Shi, Rong Ma, Zhongping Zhang, Liangping Luo

Patients with type 2 diabetes mellitus (T2DM) and there relatives with high risk of diabetes both demonstrate atrophy in right temporal and left insular lobesin. Furthermore, the decrease of cerebral blood flow (CBF) was more popular in the right temporal lobe for high risk group other than T2DM patients 

Matthew Borzage, Skorn Ponrartana, Wende Gibbs, Hollie Lai, Marvin Nelson, Benita Tamrazi, Gordon McComb, Stefan Blüml

We compared the quality of CSF flow images of ten subjects acquired with T2-weighted flow-void, phase-contrast, and tag-based MR methods. Tag-based methods included the variable image contrast TimeSLIP sequence and a newly designed method, termed TimeSTAMP, with constant contrast. Five radiologists and one neurosurgeon rated them on usefulness for identifying flow with a Likert scale: 5=highest to 1=lowest. Flow was detectable with high confidence for TimeSLIP and TimeSTAMP (4.8 ± 0.2), confidence was significantly lower (p<0.0001) in flow-void (2.5 ± 0.7) and phase-contrast (2.6 ± 0.5) images. 

Kaibao Sun, Jianfei Cui, Zhongwei Chen, Tao Jiang, Zhentao Zuo, Rong Xue, Yan Zhuo, Bo Wang, Shuli Liang, Lin Chen

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease. 90% of patients with TSC suffer from epilepsy and 50% of them become medicine intractable epilepsy. Epilepsy surgery is an important treatment. However, some focal epileptogenic lesions, essential for surgery, are not well identified by current routine imaging protocols at 3T. 7T MR imaging is assessed in this study to allow better characterization of lesion details and to detect abnormalities previously unseen on 3T MRI and scalp electroencephalogram (EEG). This is the first report of clinical application of 7T MRI for pediatric patients (older than 8 years) with TSC epilepsy.

Codi Gharagouzloo, Chao Ma, Eline Verwer, Joseph Mandeville, Chuan Huang, Srinivas Sridhar, Georges El Fakhri, Dustin Wooten, Marc Normandin

Functional MR neuroimaging is an essential tool for studying brain activity. Cerebral blood volume (CBV) is an important indicator of brain function, but measurements are typically qualitative or relative. Furthermore, warping and signal drift necessitate significant image pre-processing with standard EPI acquisition. In this work, we utilize a radial 3D UTE pulse sequence with optimized acquisition parameters determined from phantoms and modeling. Feasibility of dynamic UTE as a functional neuroimaging method is demonstrated in non-human primates receiving NBOH-2C-CN, a 5-HT_2A receptor agonist. CBV is measured dynamically throughout the whole brain and shown to agree well with an analogous EPI experiment.