Leo Hebbelmann¹, Lydia Wachsmuth¹, Henriette Lambers¹, Cornelius Faber¹, Annika Lüttjohann², and Thomas Budde^2
1Translational Research Imaging Center Clinic for Radiology, University of Münster, Münster, Germany, ²Physiology I, University of Münster, Münster, Germany

Resting-state fMRI under Isoflurane was performed to characterize brain networks in 4 and 8 month old Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and in non-epileptic controls (NEC).  Graph theoretical analysis identified major differences in intra-thalamic connectivity with age and compared to NEC, indicating that thalamus is strongly involved and probably modulated by frequently occurring seizures. In contrast, in NEC, brain networks did not change considerably in the age range studied.

Ernest Eng¹, Raimo Salo¹, Heikki Tanila¹, Mikko Kettunen¹, and Olli Gröhn^1
1A.I. Virtanen Institute for Molecular Sciences, Finland, Kuopio, Finland

The hTau.P301S-Tg mouse is an excellent model to study human tauopathy but knowledge about how tau affects the microstructure remains limited. We therefore performed anatomical and diffusion MRI to uncover structural regions likely affected by tauopathy and to characterise its progression. No initial morphometrical differences were found at 2.5 months of age. However, at 5 months, hTau.P301S mice exhibited local volumetric cerebellar changes and significantly lower FA and AD values, but higher RD values in inter-cerebellar fibres. Our data indicates that tauopathy results in structural and microstructural changes in the inter-cerebellar fibres, and possibly associates with the model’s motor declines.   

Chongxue Bie^1,2,3, Yang Zhou⁴, Peter C. M. van Zijl^1,2, Jiadi Xu^1,2, Ramon C. Sun⁵, Matthew S. Gentry6⁶, and Nirbhay N. Yadav^1,2
1The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Information Science and Technology, Northwest University, Xi'an, China, ⁴Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, ⁵Department of Neuroscience, University of Kentucky, Lexington, KY, United States, ⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, United States

Lafora disease (LD) is a glycogen storage disease marked by an intracellular accumulation of starch-like polyglucosan “Lafora bodies” (LBs) in brain and other tissues. There are no non-invasive approaches to quickly image brain glycogen and biopsies are difficult. We evaluate the feasibility of glycoNOE MRI to detect the accumulation of LBs in a laforin-deficient (Epm2a-/-) LD mouse model for this disease. Results suggest that the distribution of LBs in the brain can be mapped using glycoNOE MRI showing potential for studying this disease and its treatment non-invasively in vivo.

Byeong-Yeul Lee¹, Jeffrey M. Solomon², Marcelo Castro¹, Dong-Yun Kim³, Joseph Laux¹, Becky Reeder¹, Richard S. Bennett¹, Dima Hammoud^4,5, and Ji Hyun Lee^1
1Integrated Research Facility at Fort Detrick, Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, United States, ²Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, United States, ³Office of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, MD, United States, ⁴Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States, ⁵Center for Infectious Disease Imaging, National Institutes of Health, Bethesda, MD, United States

The goal of this study was to perform quantitative neuroimaging of rhesus monkey brains following exposure with Ebola virus (EBOV) via the intramuscular route. Using a high-resolution T1 relaxometry technique, we observed a significant increase in T1 values in the late stage (days 5-7 post inoculation). The most affected regions included the prefrontal-basal ganglia-cerebella pathway. These results are suggestive of CNS involvement in  EBOV and provide new insights into the underlying pathophysiology in the brain.

Rakshit Dadarwal^1,2, Judith Mylius¹, and Susann Boretius^1,2,3
1Functional Imaging Laboratory, German Primate Center, Göttingen, Germany, ²Georg August Universität Göttingen, Göttingen, Germany, ³Leibniz Science Campus Primate Cognition, Göttingen, Germany

QSM and R₂^* both are promising MRI methods to detect subtle variations in tissue composition. The present study demonstrates the potential of QSM and R₂^* to characterize healthy brain aging in macaques and marmosets.

Jean-Baptiste Pérot¹, Marina Célestine¹, Miriam Riquelme-Pérez¹, Carole Escartin¹, Marc Dhenain¹, Emmanuel Brouillet¹, and Julien Flament^1
1Université Paris-Saclay, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Molecular Imaging Research Center (MIRCen), Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France

Huntington’s Disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats on the exon 1 of the HTT gene.  Atrophy of the striatum is currently the main biomarker of the disease’s progression, but there is a need to find earlier and more functional biomarkers. Here, we evaluated Diffusion Tensor Imaging (DTI) and resting-state fMRI (rs-fMRI) as biomarkers in heterozygous zQ175 mice, a model mimicking the presymptomatic phase of HD. Our protocol allowed detection of vulnerable brain networks that would be of great interest for better understanding of the pathogenesis in clinical HD.

Talaignair N Venkatraman¹, Ouyang Chen², Allen W Song³, Ru-Rong Ji², and Christopher D Lascola^1
1Radiology, Duke University Medical Center, Durham, NC, United States, ²Neurobiology, Duke University Medical Center, Durham, NC, United States, ³BIAC, Duke University Medical Center, Durham, NC, United States

A high resolution tractographic ROI analysis was carried out on   ex vivo brain in mice with cutaneous T-cell lymphoma (CTCL), a mouse model of chronic pruritis. Our results show statistically significant differences between CTCL and control mice in DTI markers of fiber tract integrity and fiber number primarily involving the thalamus and hippocampus.

Tomokazu Tsurugizawa¹, Yuki Nakamura^2,3,4, Yukari Nakamura^2,3,4, Assunta Pelosi^2,3,4, Boucif Djemai⁵, Clement Debacker⁶, Jean-Antoine Girault^2,3,4, and Denis Herve^2,4,7
1Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan, ²Inserm UMR-S 1270, Paris, France, ³Sciences and Technology Faculty, Sorbonne Universite, Paris, France, ⁴Institut du Fer à Moulin, Paris, France, ⁵NeuroSpin/CEA-Saclay, Gif-sur-Yvette, France, ⁶Inserm, UMR1266, Paris, France, ⁷Sorbonne Universite, Paris, France

Despite a few studies, our knowledge of functional connectivity in the basal ganglia-thalamo-cortical loop remains incomplete in Parkinson’s disease mouse model. Here, we investigated alterations of functional connectivity and white matter structure in a hemi-parkinsonian mouse model. We found that the fractional anisotropy significantly decreased in the lesioned side in the subthalamic nucleus, such as medio-dorsal nucleus and centromedian nucleus of thalamus. The functional connectivity in the ipsilateral thalamic nuclei was also decreased in hemiparkinsonian mice. These results indicate that ipsilateral thalamic nuclei are key regions for functional and structural alterations in basal ganglia-thalamo-cortical loop in hemiparkinsonian mice.

Nicholas Vidas-Guscic¹, Johan Van Audekerke¹, Ben Jeurissen², Jasmien Orije¹, Tamara Vasilkovska¹, Dorian Pustina³, Haiying Tang³, Roger Cachope³, Longbin Liu³, Mette Skinbjerg³, Celia Dominguez³, Ignacio Munoz-Sanjuan³, Annemie Van der Linden¹, and Marleen Verhoye^1
1Bio-Imaging Lab, university of Antwerp, Antwerp, Belgium, ²Vision Lab, university of Antwerp, Antwerp, Belgium, ³CHDI foundation, Princeton, NJ, United States

Huntington’s disease (HD) is a debilitating neurodegenerative disease that affects the motor and cognitive abilities of patients. Diffusion-weighted imaging is often used in clinical evaluation of neurodegenerative disorders and recently a fixel-based analysis method was developed to analyse diffusion data. We implemented a multi-shell diffusion weighted acquisition and analysis in the zQ175 HD model. The results of the whole-brain and region-based diffusion tensor, diffusion kurtosis and fixel-based analysis indicate the presence of micro- and macrostructural differences in the zQ175 HD model in overall white matter fibers that can be attributed to significant changes in many fiber populations throughout the brain. 

Nan-Hao Chen^1,2, Kuan-Hung Cho², Yi-Ping Chao^3,4, Sheng-Min Huang², Norihiro Sadato⁵, Li-Wei Kuo^2,6, and Masaki Fukunaga^5
1Biomedical engineering and Environmental sciences, National Tsing Hua University, Hsinchu, Taiwan, ²Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan, ³Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan, Taiwan, ⁴Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan, ⁵Division of Cerebral Integration, Department of System Neuroscience, National Institute for Physiological Sciences, Okazaki, Japan, ⁶Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan

Diffusion spectrum imaging (DSI) is a model-free diffusion MRI technique capable of resolving complex fiber orientations. The capability of DSI at different field strengths and spatial resolutions remains unexplored. This study aimed to investigate the reproducibility of DSI quantified by orientational similarity and deviation angle at 3T and 7T. Our results show that DSI reproducibility at 3T and 7T for single-fiber group are comparable, whereas DSI at 7T could provide relatively better reproducibility than that at 3T for crossing-fiber group. The comparison of spatial resolutions for crossing-fiber group suggests that partial volume effect may be less dominant than signal-to-noise ratio.

Yuning Gu¹, Lulu Wang², Hongyi Yang², Yun Wu², Yong Chen³, Kai Zhong², and Xin Yu^1,3,4
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China, ³Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁴Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

A 3D MRF method was developed for T₁ and T₂ mapping of the entire monkey brain with high spatial resolution (0.35x0.35x1 mm³).  A conformal head coil was used for improved SNR, which enabled a 24-fold acceleration in data acquisition. B₁ inhomogeneity was corrected in dictionary matching.  Comparison of the T₁ and T₂ maps showed a ~20% reduction of T₂ in the globus pallidus of 6-year-old monkeys compared to 4-year-old monkeys.

Li Liu¹, Stephen Dodd¹, Ryan Hunt¹, Nikorn Pothayee¹, Nadia Nadia Bouraoud¹, Dragan Maric¹, E Ashley Moseman¹, Dorian B McGavern¹, and Alan P Koretsky^1
1National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, United States

MRI was used to follow bleeding and T cell infiltration in mouse model of nasal infection of the brain with VSV.  Microbleeds were identified as an early pathological and neuroimaging marker using high-resolution T₂*-weighted MRI. Adoptive transfer of virus specific CD8 T cells helped clear VSV, decreased microbleeds but did not stop all microbleeds.  Labeling T cells with MPIOs enabled MRI cell tracking and showed the earliest T cell infiltration in the brain. CD8 T cell infiltration and vessel rupture happened 1-day post-infection at glomerular layer, while T cells could be detected at the center of bulb before vessel breakdown.

Lei Wei¹, Ming Ding¹, Xiao Xiao¹, and He Wang^1,2
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, shanghai, China, ²Human Phenome Institute, Fudan University, Shanghai, China, Shanghai, China

In our study, we used the ultra-high field magnetic imaging to show the brain functional and structure has changed in the rats of  chronic  pain model. then we also find the expression levels of the protein marker p-Erk has changed in some brain region, including insula, NAc, S1 and so on, and insula has been shown more significant activation. This results are same to the MRI functional data analysis. Finally, we hope to combine MRI and cell imaging technique could to verify the importance of insula in non-human chronic pain.

Maëlig Chauvel¹, Ivy Uszynski¹, William Hopkins², Jean-François Mangin¹, and Cyril Poupon^1
1Université Paris-Saclay, CEA, CNRS, BAOBAB, Neurospin, Gif-sur-Yvette, France, ²Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United States

A way to better appreciate the ancient or evolved Homo sapiens brain characteristics relies on comparative investigations with homologous species. Chimpanzees remain our closest living hominid relatives, making it a pertinent model for brain studies. Few investigations address the structural connectivity of the chimpanzee brain, whereas its proximity with humans could be key to understanding the human brain. Thanks to the unique imaging data collection provided by the National Yerkes Primate Research Center and the access to elaborated diffusion MRI tools to investigate brain connectivity, we propose a novel long bundle atlas of the white matter of the chimpanzee brain.

Patrick McCunn¹, Xiaoyun Xu², Alex Li², Arthur Brown², and Robert Bartha^2
1Patrick McCunn, SickKids Research Institute, Toronto, ON, Canada, ²Robarts Research Institute, London, ON, Canada

Identification of immediate microstructural changes following repetitive mild traumatic brain injury (mTBI) could shed light on the pathophysiology of second impact syndrome. The purpose of this study was to apply Neurite Orientation Dispersion and Density Imaging (NODDI) to a preclinical model of repetitive mTBI. In the corpus callosum, neurite density index (NDI) showed a significant increase within two hours following both the first and second injury, while orientation dispersion index (ODI) showed an increase after the first injury only. These results suggest an early microstructural response to repetitive mTBI which may follow a dose-dependent like response.

Ling-Yun Fan¹, Hsu-Lei Lee¹, Robert Sullivan¹, Elizabeth Coulson^1,2, Juan Carlos Polanco^1,2, and Kai-Hsiang Chuang^1,3
1Queensland Brain Institute, University of Queensland, St Lucia, Australia, ²Clem Jones Centre for Ageing Dementia Research, University of Queensland, St Lucia, Australia, ³Centre for Advanced Imaging, University of Queensland, St Lucia, Australia

Although pre-tangle stage of tauopathy is regarded as an important pathogenic factor in neurodegenerative disease, their relationship with brain functional connectivity (FC) is still ambiguous. We investigated a tau mouse (rTg4510) model at 2.5 month-old age by resting-state functional MRI, spatial memory task and histopathology. We found increased FC between hippocampus and medial temporal area in rTg4510. Moreover, increased FC is negatively related to learning performance even though the memory is intact. On pathology, there is little phosphorylated tau over temporal areas. Our results suggest FC alternation may be an early sign of neural dysfunction at pre-tangle stage.

Yujian Diao^1,2,3, Rolf Gruetter³, and Ileana O. Jelescu^1,2
1CIBM Center for Biomedical Imaging, Lausanne, Switzerland, ²Animal Imaging and Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Impaired brain glucose consumption is a possible trigger of Alzheimer’s disease (AD). Previous work revealed affected brain structure and function by insulin resistance in terms of altered static functional connectivity (FC) in an intracerebroventricular-streptozotocin (icv-STZ) rat model of AD. Here, we used the co-activation patterns (CAP) method, a dynamic FC approach, to assess differences between icv-STZ rats and healthy controls. STZ rats displayed early higher predominance of states involving brain regions shown as hyperconnected by the static FC analysis. Longitudinally, specific brain states declined in the STZ rats only.

Yuki Asada¹, Luke Xie², Skander Jemaa³, Kai H. Barck², Tracy Yuen⁴, Richard A.D. Carano³, and Gregory Z. Ferl^1
1Pharmacokinetics & Pharmacodynamics, Genentech, Inc., South San Francisco, CA, United States, ²Biomedical Imaging, Genentech, Inc., South San Francisco, CA, United States, ³PHC Data Science Imaging, Genentech, Inc., South San Francisco, CA, United States, ⁴Neuroscience, Genentech, Inc., South San Francisco, CA, United States

Here, we trained and evaluated a fully convolutional neural network for 3D images to automatically segment brain lesions in MRI images of a cuprizone mouse model of multiple sclerosis.  To improve performance, several pre-processing and data augmentation methods were tested and compared.  The impact of lesion size on network performance was evaluated and we applied the trained segmentation model to images from non-lesion control mice to assess the capacity of the network to detect the presence or absence of lesions.  We conclude that the trained network can 1) detect the presence of a lesion and 2) accurately segment the volume.

Ziqi Yu¹, Yuting Zhai¹, Wenjing Xu¹, Xiang Chen¹, and Xiao-Yong Zhang^1
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China

Skull stripping of the mouse brain on MR images is a crucial step for rodent neuroimaging preprocessing. The traditional methods for this task are time-consuming. To solve the problem, we present a deep learning model, U-Net with Nonlocal Position-aware (NPA) block using domain knowledge transfer. The results demonstrated that our end-to-end method achieves high dice scores in several MR modalities with ultrafast processing speed which is two orders of magnitude faster than atlas-based methods. To conclude, our automatic skull stripping approach may provide an alternative to previous complex preprocessing pipelines for high-throughput rodent neuroimaging applications.

Andreea Hertanu^1,2, Cem Karakus^3,4, Lucas Soustelle^1,2, Victor N. D. Carvalho^1,2,5, Gopal Varma⁶, David C. Alsop⁶, Bilal El Waly^3,4, Olivier M. Girard^1,2, Franck Debarbieux^3,4, and Guillaume Duhamel^1,2
1Aix Marseille Univ, CNRS, CRMBM, Marseille, France, ²APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France, ³Aix Marseille Univ, CNRS, INT, Marseille, France, ⁴Aix Marseille Univ, CNRS, CERIMED, Marseille, France, ⁵Aix Marseille Univ, CNRS, ICR, Marseille, France, ⁶Division of MR Research, Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Intoxication of oligodendrocytes with lysophosphatidylcholine (LPC) is a useful model for the study of focal demyelination and more recently, neuronal damage. We propose an ihMT-CARS analysis on a rodent model of LPC-induced demyelination and a quantitative (T₁, T₂ and T_1D, the dipolar relaxation time) characterization of the demyelinated area.