Zhiva Skachokova¹, Felix Schlegel¹, Horea-Ioan Ioanas¹, Aileen Schroeter¹, and Markus Rudin^1,2
1ETH Zurich, Zurich, Switzerland, ²University of Zurich, Zurich, Switzerland

How is the BOLD fMRI signal generated still remains unclear. By using a combination of simultaneous calcium imaging and fMRI, we studied the involvement of both astrocytes and neurons in blood flow regulation during electrical hindpaw stimulation in mice. The observed response duration varies based on the anesthesia used, however a strong correlation between astrocytic calcium and BOLD signal was present. Our method allows the study of neurovascular coupling mechanisms in the intact brain and points to the importance of astrocytes in this process, and can be further used to study BOLD signal alterations e.g. in models of neurodegeneration.

Maxime Leclercq¹, Jean Christophe Deloulme², Michèle Bertacchi³, Michèle Studer³, and Hana Lahrech^1
1BrainTech Lab Inserm U1205, Grenoble, France, ²GIN Inserm U836, Grenoble, France, ³iBV Inserm U1091, Nice, France

Microscopic 3D-DTI was applied to detect brain connection defects in COUP-TFI-mutant mice. Several tractography abnormalities were identified supporting a major role of COUP-TFI gene acting in the formation and guidance of forebrain commissures. DTI results are in agreement with those using fluorescent dyes, but identifies deficiencies of other cortical tracts not previously described. As COUP-TFI (NR2F1 in humans) mutations were also linked to a complex neurodevelopmental disease in humans, this work underlines the interest of 3D-DTI to study the whole brain in patients as those affected with Bosch-Boonstra-Schaaf optic-atrophy syndrome due to NR2F1 gene mutations/deletions, an emerging rare neurodevelopmental disease.

Yuhei Takado¹, Maiko Ono², Keiichiro Minatohara², Masafumi Shimojo², Nobuhiro Nitta², Sayaka Shibata², Naruhiko Sahara², Ichio Aoki², Masato Hasegawa³, and Makoto Higuchi^2
1Department of Functional Brain Imaging Research, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan, ²National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan, ³Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

To develop therapeutic strategies, in vivo detection of the early pathological changes in Parkinson’s disease is critically important. In this work, we aimed to detect early pathological changes caused by the propagation of α-synuclein in mouse brain using MRS. Recombinant α-synuclein and fibrils were prepared and injected into C57BL6 mice. 8 weeks after the injection, glutamate levels were decreased significantly compared to saline-injected control mice, which was in accordance with decreased synapsin staining in the cortex. We demonstrated that MRS can detect synaptic dysfunction caused by α-synuclein propagation in vivo.

Zhiliang Wei^1,2, Jiadi Xu^1,2, Kerstin E. Braunstein³, Lin Chen^1,2, Tong Li³, Philip C. Wong³, and Hanzhang Lu^1,2,4
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Alzheimer’s disease (AD) has been the leading cause of cognitive impairment and decline in elder individuals. Cross-sectional human studies have reported declined cerebral oxygen metabolism in AD patients tentatively attributed to reduced neuron cells. However, longitudinal change in oxygen metabolism remains unclear. We, therefore, performed a multi-modality (MRI, behavior test, and histology) study on a novel AD mouse model, dubbed as Tau4RΔK-AP, which largely mimics the pathological processes of tau-tangles and amyloid plaques as in human AD. Enhanced oxygen metabolism has been found in Tau4RΔK-AP mice, possibly indicating a compensatory response or an inefficiency of the brain energy consumption.

F. Andrew Bagdasarian^1,2, Shannon Helsper^1,2, Xuegang Yuan^1,2, Jens T. Rosenberg¹, and Samuel Colles Grant^1,2
1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, ²Chemical & Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, United States

This study extends diffusion weighted imaging at 21.1-T to identify the pattern of potential recovery of apparent diffusion coefficient (ADC) in rodent ischemic stroke with novel stem cell therapy using dissociated aggregate human mesenchymal stem cells (d-hMSC) from different donors. All scanning was performed at 21.1 T with the goal of quantitatively assessing treatment efficacy longitudinally, spanning a 3 weeks post ischemia. Results show donor resultant ADC discrepancies at various time points and regions.

Warda Syeda^1,2,3, Charlotte Ermine¹, David Wright⁴, Vanessa Brait¹, Lachlan Thompson¹, Jess Nithianantharajah¹, Scott Kolbe⁴, Leigh Johnston^1,2, and Amy Brodtmann^1
1The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia, ²The Melbourne Brain Centre Imaging Unit, The University of Melbourne, Melborne, Australia, ³Melbourne Neuropsychiatry Centre, The University of Melbourne, Melborne, Australia, ⁴Department of Neuroscience, Monash University, Melbourne, Australia

Accumulating clinical evidence suggests remote neurodegeneration occurs in non-ischemic brain regions distant to the site of infarction in stroke, driven by both axonal degeneration and global brain inflammation. Prior preclinical studies of remote degeneration have mainly focused on brain changes over a few days or weeks post-stroke. We investigated long-term structural brain changes in an endothelin-1 model of mild focal ischemic stroke in rats, using a clinically relevant period of 48-weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We found significant cortical atrophy and white matter alterations, suggesting widespread stroke-related degenerations.

Cheng-Yu Chen^1,2,3,4, Po-Chih Kuo⁵, Yung-Chieh Chen¹, Yu-Chieh Jill Kao², Ching-Yen Lee⁶, Hsiao-Wen Chung⁷, and Duen-Pang Kuo^1
1Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, ²Translational Imaging Research Center, Taipei, Taiwan, ³Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ⁴Radiogenomic Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ⁵Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, ⁶TMU Research Center for Artifical Intelligence in Medicine, Taipei, Taiwan, ⁷Graduate Institute of Biomedical Electrics and Bioinformatics, National Taiwan University, Taipei, Taiwan

In the present study, we developed a 2-level classification model with an overall accuracy of 88.1 ± 6.7% for discriminating the stroke hemisphere into the infarct core (IC), ischemic penumbra (IP), and normal tissue regions on a voxel-wise basis in a permanent left middle cerebral artery occlusion model. According to the analysis results, we suggest that a single diffusion tensor imaging (DTI) sequence combined with machine learning (ML) algorithms can dichotomize ischemic tissue into the IC and IP, which are comparable to the conventional perfusion–diffusion mismatch.

Marina Khodanovich¹, Ilya Gubskiy ², Darya Namestnikova ², Marina Kudabaeva¹, Valentina Glazacheva¹, Tatyana Anan'ina¹, and Vasily Yarnykh^1,3
1Tomsk State University, Tomsk, Russian Federation, ²Pirogov Russian National Research Medical University, Moscow, Russian Federation, ³University of Washington, Seattle, WA, United States

The study, performed on a rat model of ischemic stroke, aimed to evaluate a recently proposed myelin biomarker, macromolecular proton fraction (MPF) as a non-invasive tool for monitoring recovery after stroke. Longitudinal observations showed the different time courses of MPF evolution in the infarct zones undergoing subsequent demyelination (DZ) or remyelination (RZ). After a sharp decrease at days 1-5 after MCAO, MPF showed a further decline in the DZ and a restoration in the RZ to day 56. These findings were confirmed by histology which showed similar tissue evolution zones and enhancement of neurogenesis and oligodendrogenesis in the ischemic core.

Marlene Wiart¹, Maryna Basalay², Fabien Chauveau³, Chloe Dumot¹, Christelle Leon¹, Camille Amaz⁴, Radu Bolbos⁵, Diana Cash⁶, Eugene Kim⁶, Tae-Hee Cho⁷, Norbert Nighoghossian⁷, Sean Davidson², Michel Ovize¹, and Derek Yellon^2
1Université Lyon, CarMeN laboratory, Inserm U1060, Lyon, France, ²The Hatter Cardiovascular Institute, London, United Kingdom, ³Université Lyon, Lyon Neuroscience Research Center, CNRS UMR5292, Inserm U1028, Lyon, France, ⁴Clinical Investigation Center, HCL, Lyon, France, ⁵CERMEP-Imagerie du Vivant, Bron, France, ⁶Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, ⁷Stroke Medicine, Université Lyon, CREATIS CNRS UMR 5220-INSERM U1206, Lyon, France

The main objective of this study was to test the neuroprotective effects of remote ischemic conditioning (RIC: 4 cycles of 5-min hind limb ischemia interleaved with 5-min reperfusion) in a rat model of transient ischemic stroke (90 minutes) in a two-center study using translational MR imaging endpoints. Neuroscores and edema-corrected infarct size measured at 24h on T2-weighted MRI and expressed as percentage of the area at risk on per-occlusion MRI were significantly reduced in the RIC-treated group compared to the control group. The use of longitudinal MRI increases results robustness, which is greatly needed for successful RIC clinical translation.

Grzegorz Kwiatkowski¹, Georgios Louloudis¹, Jan Klohs¹, and Sebastian Kozerke^2
1Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland, ²ETH Zurich, Zurich, Switzerland

Quantitative analysis of magnetization transfer (qMT) based on a two-pool model was employed to characterized changes in the mouse brain following a transient middle cerebral artery occlusion (tMCAO) model of cerebral ischemia.The changes in qMT were compared to the standard MR metrics of an ischemic lesion (T₁, T₂, ADC, FLAIR) to examine the possible overlap of mechanisms affecting these magnetic resonance imaging contrasts. Notable changes of all MR metrics were found in the brain of the tMCAO group while only the qMT analysis revealed significant alterations in the sham-operated animals.

Yu-Chieh Jill Kao^1,2,3, Chia-Feng Lu⁴, Bao-Yu Hsieh⁵, and Cheng-Yu Chen^1,2,3,6
1Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan, ²Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ³Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ⁴Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ⁵Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, ⁶Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan

Significant improvement of locomotor activity and anxiety-like behavior along with reorganization of motor and default mode network was observed after NAC or NAC plus MINO treatment after repetitive closed-head injury, suggesting tentative treatment using drugs in patients with repetitive mild traumatic brain injury.

Dan Benjamini^1,2, Michal Komlosh^1,2, Elizabeth Hutchinson³, and Peter Basser^1
1National Institutes of Health, Bethesda, MD, United States, ²Uniformed Service University of the Health Sciences, Bethesda, MD, United States, ³The University of Arizona, Tucson, AZ, United States

Diffusion MRI techniques that extend beyond diffusion tensor imaging (DTI) – including double diffusion encoding (DDE) – could provide more specific tools to probe abnormalities in disease or injury states. Here, DDE is applied to reveal the diffusion correlation spectrum on a voxelwise basis, which allows to directly assess the microscopic anisotropy in healthy and injured ferret spinal cords.

Praveen Kulkarni¹, Ju Qiao², and Craig Ferris^1
1Psychology, Northeastern University, Boston, MA, United States, ²A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

Failure in the blood brain barrier (BBB) lies at the foundation of small vessel disease that is precursor to neurodegenerative diseases. There are multiple risk factors leading to increased permeability in the BBB; one prevalent risk factor is repetitive mild TBI.  Imaging the subtle changes in BBB permeability is not possible with standard imaging protocols. With quantitative ultra-short time-to-echo, contrast-enhanced (QUTE-CE) MRI, using the superparamagnetic iron oxide nanoparticle ferumoxytol, we can image changes in BBB permeability following rmTBI. With this novel methodology we can measure the immediate effects of rmTBI on changes in BBB permeability across the entire rat brain.

Abdalla Z Mohamed¹ and Fatima Abdalla Nasrallah^1
1Queensland Brain institute, The University of Queensland, Brisbane, Australia

Traumatic brain injury (TBI) is a severe problem worldwide. The non-invasive investigation of the microstructural alterations is of significant benefit for early diagnosis and interventions. In this study, we applied diffusion tensor imaging (DTI) to monitor the longitudinal microstructural changes in a controlled cortical impact rodent model of TBI from 2 hours and up to 6 months post-injury. Using DTI, we observe ongoing white matter changes following TBI, that initiate in corpus callosum and injury location at early timepoints and persists to exist up to 6 months, suggesting the temporal sensitivity of DTI to detect ongoing microstructural changes following TBI.  

Hannes M. Wiesner¹, Wei Zhu¹, Yi Zhang¹, Manuel Esguerra², Colleen Hutchison², Mark J. Thomas², Xiao-Hong Zhu¹, and Wei Chen^1
1Department of Radiology, CMRR, University of Minnesota Medical School, Minneapolis, MN, United States, ²Departments of Neuroscience and Psychology, University of Minnesota, Minneapolis, MN, United States

Resting state fMRI (rs-fMRI) has been used to investigate alcohol use disorder (AUD), mostly in humans; and a wide array of commonly induced neurological changes due to acute and chronic use have been reported. In this work, we established a rat model of AUD to longitudinally study the effects of chronic alcohol abuse on the functional brain connectivity using rs-fMRI at ultrahigh fields. Preliminary results revealed potential changes in reward-processing circuit connectivity and global brain activity. Further research is advised to quantify early effects observed in and between different neural structures (NAc/IBST/PreL/IL and ACC) during withdrawal stress and relapse.

Yu Song^1,2, Hongbin Han^2,3,4, Qingwei Song¹, Yajuan Gao^2,3,4, Rui Wang^2,3,4, Xianjie Cai^2,3,4, Yumeng Cheng^2,3,4, and Zeqing Tang^2,3,4
1Department of Radiology, the First Affiliated Hospital of Dalian Medical University, Dalian, China, ²Key Laboratory of Magnetic Resonance Imaging Equipment and Technique, Beijing, China, ³Department of Radiology, Peking University Third Hospital, Beijing, China, ⁴Institute of Medical Technology（IMT）of Peking University Health Science Center（PKUHSC）, Beijing, China

Delivering pharmacologic agents directly into the brain has been proposed as a means of bypassing the blood brain barrier. Within this study we propose a novel system for delivering drugs into the brain named the simple diffusion (SDD) system. To validate this technique, rats were subjected to a sin- gle intracranial (at the caudate nucleus), or intraperitoneal injection, of the compound citicoline, followed two hours later by a permanent middle cerebral artery occlusion (pMCAO).  These results suggest that given the appropriate injection point, through SDD a pharmacologically effective concentration of citicoline can be administered.

Gustavo Chau Loo Kung¹, Juliet Knowles², Erpeng Dai³, John Huguenard², Michelle Monje², and Jennifer McNab^3
1Bioengineering Department, Stanford University, Stanford, CA, United States, ²Neurology Department, Stanford University, Stanford, CA, United States, ³Radiology Department, Stanford University, Stanford, CA, United States

A previously unexplored possibility is that maladaptive myelination may contribute to both the predisposition to seizures and cognitive impairment in diseases such as absence epilepsy. This work presents MRI white matter microstructural measurements in ex vivo mouse brains from the  Scn8amed+/- model of absence epilepsy. We obtained estimates of fractional anisotropy, myelin volume fraction and g-ratio. Our results are suggestive of thicker myelin sheaths, which is consistent with g-ratio data obtained by electron microscopy. We look to expand the current analysis to perform longitudinal measurements of the evolution of this particular type of epilepsy and its interplay with aberrant myelination. 

Aline M. Thomas^1,2, Peter A. Calabresi^3,4, Michael T. McMahon^1,5, Peter C.M. van Zijl^1,5, and Jeff W.M. Bulte^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Institute for Cell Engineering, Imaging Section and Vascular Biology Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵Department of Radiology, Kennedy Krieger Institute, Baltimore, MD, United States

In multiple sclerosis (MS), immune cells damage the brain and spinal cord, often causing irreversible disability. Current imaging strategies visualize the resulting damage, but the heterogeneity of the damage observed complicates image interpretation. Evidence has emerged that the immunological attacks in MS are initiated in central nervous system-draining lymph nodes. Here, we demonstrate the potential of chemical exchange saturation transfer (CEST) MRI to monitor changes in these lymph nodes as disability progressed in a mouse model of experimental autoimmune encephalomyelitis.

Fangrong Zong¹, Yan Zhuo^2,3, Chengya Dong⁴, Baoshan Qiu⁴, Shunyin Zhao⁴, Baogui Zhang⁵, Yilong Wang⁴, and Xiangrong Liu^4
1Centre for Advanced Magnetic Resonance Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, ²State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, ³The Innovation Center of Excellence on Brain Science, Chinese Academy of Sciences, Beijing, China, ⁴China National Clinical Research Center for Neurological Diseases, Beijing, China, Beijing, China, ⁵Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China

The underlying mechanism of vascular dementia remains unclear which leads to difficulties in developing specific disease treatments. This contribution firstly developed a multi-modal MRI approach on a mouse model with unilateral carotid artery stenosis as non-invasive measures. A positive correlation was built between fractional anisotropy and cerebral blood flow under hypoperfusion conditions, which provides insights into understanding the pathological mechanism of vascular dementia.

Lin Chen^1,2, Zhiliang Wei^1,2, Kannie W.Y. Chan^1,2,3, Jianpan Huang⁴, Xiang Xu^1,2, Philip C. Wong^5,6, Hanzhang Lu^1,2, Peter C.M. van Zijl^1,2, Tong Li^5,6, and Jiadi Xu^1,2
1Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China, ⁴City University of Hong Kong, Hong Kong, China, ⁵Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁶Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States

In this study, we used onVDMP MRI to detect glucose uptake in tauopathy Alzheimer's disease (AD) mouse brain. Compared to wild-type mice, significantly reduced glucose uptake was observed in both cerebrospinal fluid (CSF) and parenchyma of AD mouse brain. Clearance of glucose through CSF was found in wild-type mice, but not in AD mice, which implicates dysfunction of the glymphatic system in AD mouse brain. The results in this study suggest that onVDMP MRI could be a cost-effective and widely available method for evaluating the functions of glucose transporter and glymphatic system, and hence diagnosing AD.

Laetitia Degiorgis¹, Marion Sourty^1,2, Julien Lamy¹, Vincent Noblet¹, Meltem Karatas^1,3,4, Thomas Bienert⁴, Marco Reisert⁴, Anne-Laurence Boutillier⁵, Jean-Paul Armspach¹, Frédéric Blanc^1,6, and Laura Harsan^1,7
1University of Strasbourg and CNRS, ICube Laboratory UMR 7357, Strasbourg, France, ²The University of Sydney, Faculty of Engineering, School of Aerospace, Mechanical and Mechatronic Engineering, Sydney, Australia, ³CNRS, University of Strasbourg, INCI, UMR 7168, Strasbourg, France, ⁴Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany, ⁵Laboratoire de Neuroscience Cognitives et Adaptatives, Strasbourg, France, ⁶University Hospital of Strasbourg, CM2R (Memory Resource and Research Centre), Day Hospital, Geriatrics Department, Strasbourg, France, ⁷Department of Biophysics and Nuclear Medicine, University Hospital of Strasbourg, Strasbourg, France

MRI is a unique tool to understand the complexity of the brain functional and structural communication evolution over time. Among the main mechanisms of AD, tauopathy remains poorly studied in preclinical imaging. We used graph theory approaches and DTI analysis in a longitudinal study of Thy-Tau22 mice, associated with behavioral evaluation. Alterations of the cholinergic septal circuitry, supporting memory and emotional processes, were found as the main hallmark of the progression of the pathology, associated with default mode network dysfunction, both starting before the first memory deficits.

Laura-Adela Harsan¹, Laetitia Degiorgis¹, Julien Todeschi², Lea Becker³, Maxence Thomas de la Pintière¹, Victor Mathis³, Chrystelle Po¹, and Ipek Yalcin^3
1ICube: Engineering science, computer science and imaging laboratory, University of Strasbourg, Strasbourg, France, ²ICube: Engineering science, computer science and imaging laboratory, Neurosurgery Department, University Hospital Strasbourg, University of Strasbourg, Strasbourg, France, ³Institute de Neurosciences Cellulaires et Intégratives, University of Strasbourg-CNRS, Strasbourg, France

The main objective of this study is to modulate and map the anterior cyngulate cortex (ACC) functional connectivity (FC) pathways underlying depression development in a mouse model. We use the optogenetic approaches to create the depression phenotype in mice, by activating the pyramidal ACC neurons expressing Channel rhodopsin 2 (ChR). We further use resting state functional MRI (rsfMRI) as non-invasive read-out of the effects at the level of functional brain connectivity. Four consecutive sessions of optogenetic ACC stimulation induced strong depression phenotype and major modifications of the functional mouse brain connectivity including perturbed mesocorticolimbic pathways and default mode network patterns

Do-Wan Lee¹, Chul-Woong Woo², Hwon Heo³, Jae-Im Kwon², Yeon Ji Chae³, Su Jung Ham⁴, Jeong Kon Kim¹, Kyung Won Kim^1,4, Dong-Cheol Woo^2,3, and Dong-Hoon Lee^5
1Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ²Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea, ³Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ⁴Asan Image Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea, ⁵Faculty of Health Sciences and Brain & Mind Centre, The University of Sydney, Sydney, Australia

Research on changes to glutamate signaling in the white matter of demyelinating diseases may provide important biophysical information for diagnostic and prognostic assessment. We attempted to evaluate glutamate signals in a cuprizone-induced rat model of demyelination by GluCEST imaging. GluCEST imaging provides in vivo image contrast of changing glutamate concentrations during demyelination and subsequent remyelination. We also performed histological validation to analyze the state of myelinated axons. GluCEST imaging could be a useful tool to evaluate brain metabolism in demyelination and remyelination models and provide quantitative results that are highly representative of changes to glutamate levels in vivo.

Lucy Liu^1,2, Andre Bongers², Lynne Bilston^1,2, and Lauriane Jugé^1,2
1Neuroscience Research Australia, Sydney, Australia, ²University of New South Wales, Sydney, Australia

Maternal infection during pregnancy can cause enlarged ventricles and compromise brain microstructure, which conventional imaging techniques cannot identify. We investigated the potential of magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) in detecting brain microstructural changes in offspring of Poly (I:C)-induced maternal immune activated rats. Results showed that DTI and MRE were sensitive to neurodevelopmental microstructural changes, but not to subtle longitudinal microstructural changes related to maternal infection. DTI showed that white matter injury differs between perinatal and adolescent Poly(I:C) rats, while MRE was not sensitive enough to detect subtle compromise of gray matter microstructure in Poly (I:C) rats.

Talaignair N Venkatraman¹, Haichen Wang², Chris Petty¹, Allen W Song¹, and Christopher D Lascola^1
1Radiology, Duke University Medical Center, Durham, NC, United States, ²Neurology, Duke University Medical Center, Durham, NC, United States

Ex-Vivo high resolution (3D) volumetric, tractographic and  connectomic analysis carried out on a mouse model of CNS Lupus at 7T. The results show strong therapeutic effect of a novel QR II inhibitor.

Kwangyeol Baek¹, Rachel Bennett², Bradley Hyman², Woo Hyun Shim³, and Young Ro Kim^4,5
1School of Biomedical Convergence Engineering, Pusan National University, Busan, Republic of Korea, ²Department of Neurology, Massachusetts General Hospital and Harvard Medical School,, Boston, MA, United States, ³Department of Radiology, Asan Medical Center, Seoul, Korea, Republic of, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ⁵Department of Radiology, Harvard Medical School, Boston, MA, United States

We assessed vascular disruption in rTg4510 mouse (age of 6 and 9 months), a tau expressing transgenic animal model of Alzheimer’s disease, using MRI metrics such as vessel size index (VSI), Gd-DTPA leakge through BBB and water exchange index (WEI). The rTg4510 mice showed age-dependent expansion of the hippocampal lesion and profound vascular alteration around the hippocampal lesion: Increase in VSI, mild Gd-DTPA leakage and increased WEI. Our findings suggest the role of vascular components in development of Alzheimer’s disease with tau pathology. Vascular MRI assessments might have a potential application in early diagnosis and monitoring of Alzheimer’s disease.

Zhenxiong Wang^1,2, Wenzhen Zhu¹, Shun Zhang¹, Guiling Zhang¹, Mehran Shaghaghi², and Kejia Cai^2
1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ²Departments of Radiology, Department of Bioengineering, and the Center for MR Research, Chicago, IL, United States

In this study we demonstrated the feasibility of longitudinal neurite orientation dispersion and density imaging (NODDI) in characterizing the microstructural alterations in rat brain tissues due to middle cerebral artery occlusion at a 3T MRI and validated the NODDI parameters with histology.

Zhiliang Wei^1,2, Qihong Wang³, Sung-Min Cho⁴, Romergryko Geocadin⁴, Hiren R. Modi³, Nitish V. Thakor³, and Hanzhang Lu^1,2,3
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Cardiac arrest (CA) is associated with low survival rate and unfavorable outcomes despite maximal medical care. For determining the timing of acute brain injury and delivering aggressive intervention at early stage to improve neurologic outcomes, an early-stage biomarker is compulsory. Here, we utilized MRI techniques to reveal the temporal trajectories of brain’s blood supply, oxygenation, and energy consumption in the first few hours following return-of-spontaneous-circulation, and found early physiologic measure is associated with 24-h neurologic deficit score. This finding may potentially facilitate the future research on CA management by providing a sensitive physiologic biomarker to determine appropriate medical intervention. 

Jing Yuan¹, Zhizheng Zhuo¹, Bing Wu², and Yaou Liu^1
1Beijing Tiantan Hospital, Capital Medical University, Beijing, China, ²GE Healthcare, China, Beijing, China

Early postoperative cerebral perfusion changes after direct revascularization surgery in moyamoya disease were studied. The preoperative and postoperative perfusion parameters from ASL and CT perfusion studied were compared based on perfusion territory showed by ssASL technique. Two types of perfusion changes were found, group I represented perfusion territory redistribution and group II represented perfusion improvement.

Claudia Falfán-Melgoza¹, Livia Asan², Johannes Knabbe², Carlo Beretta^2,3, Thomas Kuner², and Wolfgang Weber-Fahr^1
1RG Translational Imaging, Central Institute of Mental Heath, Mannheim, Germany, ²Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany, ³CellNetworks Math-Clinic, Bioquant BQ001, Heidelberg University, Heidelberg, Germany

Insights gained from Voxel Based morphometry (VBM) tremendously advance the understanding of neurologic and psychiatric diseases.  However, the cellular basis of VBM changes remains largely unclear.  We used longitudinal two-photon fluorescence and magnetic resonance imaging in mice to explore the cellular basis of VBM. Our data shows that MRI volume changes are only limited reflected by physical volume changes, yet dominated by cellular composition and cytoarchitectural characteristics. This has great implications for findings in neuroimaging in general, and the novel approach introduced by this study can be applied to various disease models to potentially unravel key mechanisms of brain pathophysiology.

Xingzheng Pan¹, Eric R. Muir², Paul J. Donaldson^1,3, Ehsan Vaghefi¹, Zhao Jiang², Caterina Sellitto⁴, and Thomas W. White^4
1School of Optometry and Vision Science, University of Auckland, Auckland, New Zealand, ²Department of Radiology, School of Medicine, Stony Brook University, Stony Brook, NY, United States, ³Department of Physiology, School of Medical Sciences, University of Auckland, Auckland, New Zealand, ⁴Department of Physiology & Biophysics, School of Medicine, Stony Brook University, Stony Brook, NY, United States

The physiological optics of the crystallin lens depend on its water content, water-bound protein ratios and surface geometry^1,2.  To maintain these properties, the lens generate a circulating flux of ions that actively removes water from the lens center via an intracellular pathway mediated by gap junction channels³.  In this study, we established and optimised T1&T2 mapping and structural scan to study the physiological optics the mouse lens at 7T. These protocols were then applied to a transgenic mouse model in which we have genetically modified the number of gap junction channels to alter the removal of water from the lens.

Frederick C. Damen¹, Steve Zaldua², Jin Gao³, Weiguo Li³, Leon Tai², and Kejia Cai^1
1Radiology, University of Illinois at Chicago, CHICAGO, IL, United States, ²Anatomy and Cell Biology, University of Illinois at Chicago, CHICAGO, IL, United States, ³Research Resources Center, University of Illinois at Chicago, CHICAGO, IL, United States

In neurodegenerative diseases, e.g., Alzheimer’s disease, it is important to study cerebral blood flow (CBF) and blood brain barrier (BBB) permeability. Arterial Spin Labeling (ASL), used to measure CBF, is hampered by physiological variability, requiring many averages, and thus, fast imaging.  Echo Planner Imaging, the most used fast imaging method, suffers from massive distortions and blurring for mice brain imaging at high field MRI. Alternatively, in this study we successfully implemented steady state free precession fast imaging for the measurement of the BBB leakage in mouse brain at 9.4T.

Paula Ramos Delgado¹, Christian Prinz¹, Jason M. Millward¹, Helmar Waiczies², Ludger Starke¹, Joao Periquito¹, Laura Boehmert¹, Thoralf Niendorf^1,3, Andreas Pohlmann¹, and Sonia Waiczies^1
1Berlin Ultrahigh Field Facility (B.U.F.F), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, ²MRI.tools GmbH, Berlin, Germany, ³Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

The low SNR inherent to fluorine (¹⁹F) MRI necessitates sensitivity-enhancing methods. SNR-efficient imaging techniques such as RARE and SNR-enhancing cryogenically-cooled RF coils (CRP) create new challenges. The strong spatially-varying B₁ fields of transceive surface RF coils hamper quantification and no analytical signal intensity equation for B₁⁺ correction exists for RARE. We developed a B₁ correction method that makes use of experimental data to model the signal intensity from RARE and we established a workflow to correct and quantify ¹⁹F MR signals originating from inflammatory regions of the mouse brain that were acquired using a ¹⁹F-CRP.

Jérémie P. Fouquet¹, Luc Tremblay¹, Andreas Deistung², Renat Sibgatulin³, Martin Krämer³, Karl-Heinz Herrmann³, Réjean Lebel¹, Jürgen R. Reichenbach³, and Martin Lepage^1
1Sherbrooke Molecular Imaging Center (CIMS), Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada, ²Faculty of Medicine, Universitätsklinikum Halle, Halle, Germany, ³Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany

Anesthetic conditions may have important effects on the blood oxygen saturation in rodents. However, the size of those effects has not been directly quantified in the mouse brain. We use Quantitative Susceptibility Mapping to provide a direct estimate of the oxygen saturation in the mouse brain under anesthesia. Three commonly used anesthetics, namely isoflurane, dexmedetomidine, and ketamine-xylazine, are evaluated. The effect of breathing gas is also evaluated.

Kwangyeol Baek¹, Chae Ri Park², Siwan Jang³, Woo Hyun Shim², and Young Ro Kim^1
1Massachusetts General Hospital, Boston, MA, United States, ²Asan Medical Center, Seoul, Korea, Republic of, ³Portsmouth Abbey School, Portsmouth, RI, United States

Resting state fMRI study in animal model often involved use of anesthetics, but the effect of anesthetics on the spontaneous neural activity is not well known. We investigated how different types and doses of anesthetics (isoflurane and α-chloralose) influence the LFP activity and functional connectivity in comparison with the awake state. We observed distinct effects of these anesthetics on spontaneous neural activity (e.g. burst-suppression pattern and nonspecific correlation for high dose of isoflurane) and evoked response (e.g. potentified sensory-evoked response in bilateral cortices with α-chloralose). The effect of anesthetics should be taken into account in animal resting state fMRI studies.

Horea-Ioan Ioanas¹, Bechara John Saab², and Markus Rudin^1
1Institute for Biomedical Engineering, ETH and University of Zurich, Zurich, Switzerland, ²Preclinical Laboratory for Translational Research into Affective Disorder, University of Zurich Psychiatric Hospital, Zurich, Switzerland

The definition of neurophenotypes for the function of key neurotransmitter systems is vital to the improvement of drug development in psychopharmacology. In this study we present a whole-brain map of stimulus-evoked VTA dopaminergic function in mice, alongside a parameter analysis for this novel assay. This study shows overall coherence between functional and known structural connectivity, but provides additional evidence for functional connectivity towards the dorsal striatum (first indicated in the rat model). We propose that this thoroughly explored new assay can provide an invaluable read-out for dopaminergic dysfunction and dopaminergic intervention modelling.

Jae-Im Kwon¹, Hwon Heo², Sang Tae Kim¹, Su Jeong Ham¹, Yeon Ji Chae¹, Young Jin Kim¹, Do-Wan Lee², Kyung Won Kim³, Dong Cheol Woo^1,2, and Chul-Woong Woo^1
1Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, Republic of, ²Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ³Radiology, Asan Medical Center, Seoul, Korea, Republic of

Emerging evidence suggests that aryl hydrocarbon receptor (AhR) antagonism could attenuate neuronal damage caused by transient ischemic stroke. However, the optimal timing of AhR antagonist administration for maximum neuroprotective efficacy has yet to be established. The present study explored this issue via MRIs in rats with transient ischemic stroke and demonstrated that infarct volume and apoptosis were alleviated in rats that received AhR antagonists 10 or 50 minutes after ischemia. In addition, the timing of AhR antagonist administration was shown to affect edema formation caused by transient ischemic stroke.

Lore M. Peeters¹, Monica Van den Berg¹, Rukun Hinz¹, and Georgios A. Keliris^1
1Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium

Understanding the role of the basal forebrain (BFB) in controlling the dynamics of brain processes is of great interest. We aimed to investigate the influence of selective unilateral stimulation of BFB cholinergic neurons on functional connectivity (FC) in the rodent default-mode like network (DMLN). By combining resting-state functional MRI (rsfMRI) with chemogenetics, we demonstrate that stimulation of the cholinergic neurons in the right BFB significantly decreased right intra-hemispheric and inter-hemispheric FC in the DMLN in rats. These findings provide new critical insights into the interplay between attentional networks and DMLN in rodents.

Marija Markicevic¹, Oliver Sturman ², Johannes Bohacek², Markus Rudin^3,4, Nicole Wenderoth¹, and Valerio Zerbi^1
1Neural Control of Movement lab, DHEST, ETH Zurich, Zurich, Switzerland, ²Laboratory of Molecular and Behavioural Neuroscience, DHEST, ETH Zurich, Zurich, Switzerland, ³Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ⁴Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

RsfMRI is used to investigate healthy and diseased brains via temporal correlations of distinct brain regions i.e. functional connectivity (FC). However, this gives little insight into the contribution of specific cell-types to the recorded signals. To tackle this, we measured rsfMRI in mice while chemogenetically exciting or inhibiting D1 expressing cells in dorsomedial striatum (dmCP) via DREADDs. Initial results illustrate opposing effects of excitation and inhibition on FC, observed only within anatomically connected nodes of corticostriatal circuitry. These results are the first, necessary step for further disentangling the role of dmCP on motor control and behavior.   

Satoshi Fujiwara¹, Sosuke Yoshinaga¹, Shigeto Iwamoto¹, Sayaka Shibata², Aiko Sekita², Nobuhiro Nitta², Tsuneo Saga², Ichio Aoki², and Hiroaki Terasawa^1
1Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan, ²Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan

Neuroinflammation is initiated by many types of neural disorders as a defensive response of the innate immune system in the central nervous system (CNS). Neuroinflammation is typically accompanied by the disruption of Ca²⁺ homeostasis. Manganese chloride (MnCl₂) is a useful positive MRI contrast agent that enters activated cells through Ca²⁺ channels, and is utilized in Manganese-Enhanced MRI (MEMRI) for functional neuroimaging. We sought to determine whether MEMRI could be used to assess the cellular/molecular alterations caused by acute neuroinflammation in vivo, by focusing on Mn²⁺ accumulation in the rodent brain.

Do-Wan Lee¹, Hwon Heo², Chul-Woong Woo³, Jae-Im Kwon³, Su Jung Ham⁴, Yeon Ji Chae², Kyung Won Kim^1,4, Jeong Kon Kim¹, Dong-Cheol Woo^2,3, and Dong-Hoon Lee^5
1Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ²Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ³Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea, ⁴Asan Image Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea, ⁵Faculty of Health Sciences and Brain & Mind Centre, The University of Sydney, Sydney, Australia

Detecting glutamate signals in vivo within the brain may have a diagnostic potential. Recently, with many translational research efforts leading to clinical trials, presenting the normal in vivo glutamate distribution in pre-clinical data to establish a database for pre-clinical studies can be valuable. In this abstract, we investigated glutamate signal distributions in multiple brain regions of a healthy rat brain using GluCEST imaging. Quantified GluCEST signals showed significant differences between white and gray matter regions. Our findings and investigations yield a valuable database and insights for comparing glutamate signal changes in pre-clinical brain diseases.

Zengmin Li¹, Hsu-Lei Lee^1,2, Elizabeth Coulson^1,3, Pankaj Sah¹, Patricio Opazo¹, and Kai-Hsiang Chuang^1,2
1Queensland Brain Institute, The University of Queensland, St Lucia, Australia, ²Centre for Advance Imaging, The University of Queensland, St Lucia, Australia, ³School of Biomedical Sciences, The University of Queensland, St Lucia, Australia

·      After spatial learning, large-scale plasticity in functional networks were detected in mice using resting-state fMRI.

·      Different training intensity recruited different functional networks.

·      Functional connectivity reorganized to be less hippocampus dependent after 1 week of consolidation.

Loi Do¹, Adam Scott Bernstein¹, Pradyumna Bharadwaj², Chidi Ugonna¹, Marc A Zempare², Nan-kuei Chen¹, Gene E Alexander², Carol A Barnes², and Theodore Trouard^1
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States, ²Psychology, University of Arizona, Tucson, AZ, United States

High resolution 3D-RARE magnetic resonance imaging (MRI) was carried out in the brain of rats (n=114) of varying ages and cognitive performance.  Volumetric comparison of total intracranial volume (TIV) and total ventricular system (TVS) was performed using an atlas based analysis.  The TIV increases from young adult to middle age but plateaus through old age.  Average body weight increases from young adult to middle age but decreases from middle age to old age. No significant difference was found in TVS volume between ages or cognitive ability.

Robin A. de Graaf¹, Monique A. Thomas¹, Kevin L. Behar², and Henk M. De Feyter^1
1Dept. of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, ²Dept. of Psychiatry, Yale University, New Haven, CT, United States

Deuterium metabolic imaging (DMI) is a novel, non-invasive method to map metabolism from deuterated substrates in 3D. The replacement of protons with deuterons could potentially lead to kinetic isotope effects (KIEs), and loss of deuterons. Knowledge of the KIE levels, and label losses is required for DMI-based measurements of absolute metabolic rates. Here the deuterium KIE and label loss is investigated for glucose and acetate in rat brain in vivo using a double substrate/double labeling strategy. Significant, but predictable and reproducible label losses were observed in the metabolic products lactate, glutamate and glutamine. The measured KIE was relatively small (4-6%).

Yuning Gu¹, Yong Chen², Jesse I. Hamilton³, Kihwan Kim¹, Ciro Ramos-Estebanez⁴, Chris A. Flask², Nicole Seiberlich^2,3, Charlie Androjna⁵, and Xin Yu^1,2,6
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, ³Department of Radiology, University of Michigan, Ann Arbor, MI, United States, ⁴Department of Neurology, Case Western Reserve University, Cleveland, OH, United States, ⁵Cleveland Clinic Pre-Clinical Magnetic Resonance Imaging Center, Cleveland Clinic Foundation, Cleveland, OH, United States, ⁶Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

Simultaneous quantification of intravenously injected Gadolinium (Gd) and ¹⁷O-water through T₁ and T₂ shortening effect enables evaluation of BBB permeability to large and small molecules under pathological conditions. Magnetic resonance fingerprinting allows fast and simultaneous T₁ and T₂ mapping, though improvement in T₂ sensitivity is required for accurate quantification of ¹⁷O-water in brain. This study demonstrates that the combination of T₂-preparation module and small flip angle improves the accuracy in T₂ estimation in mouse brain. Further, the feasibility of using MRF method to quantify Gd and ¹⁷O-water concentration was explored in a phantom study.