| 08:15 | 0047.
 | Metabolic characterization of the rat motor cortex with fMRS upon chemogenetic excitation Nathalie Just1
1DRCMR, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark, Denmark Keywords: Biology, Models, Methods, Metabolism, Chemogenetics, fMRS Motivation: To complement previous fMRI studies of interhemispheric pathways, we propose to characterize the interhemispheric metabolism using functional magnetic resonance spectroscopy (1H-fMRS). Goal(s): To demonstrate the feasibility of chemogenetic 1H-fMRS in the rat brain at 7T. Approach: DREADDs and Sham viruses were injected in the right motor cortex of rat. Neural activation was induced by a 1mg/kg IP bolus of Clozapine-N Oxide (CNO). Spectra were acquired continuously prior and following CNO injection and quantified with a temporal resolution of 5 minutes. Results: Relative concentration changes were found for myo-Inositol, Taurine, Glutamate and NAA in the motor cortex of chemo-induced rats following CNO injection. Impact: Functional metabolic findings will greatly complement our knowledge of interhemispheric pathway allowing a better understanding of long-distance circuits known to initiate both excitation and inhibition. |
| 08:27 | 0048.
 | Establishment, behavioral, structural and functional characterization of a hindlimb amputation model in mice with multimodal MRI and MRS Claudia Falfán-Melgoza1, Carmen La Porta2, Anke Tappe-Theodor2, and Wolfgang Weber-Fahr1
1RG Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, 2Pharmacology institute, Medical Faculty, University of Heidelberg, Heidelberg, Germany Keywords: Small Animals, Spectroscopy Motivation: Limb amputation frequently leads to pain in residual limb and phantom sensations, but there is no comprehensively described mouse model for translational research. Goal(s): To extensively phenotype a mouse model of limb amputation to investigate contributing factors of pain. Approach: Behavioral characterization and multimodal in vivo brain imaging (Voxel-based Morphometry, resting-state functional Magnetic Resonance Imaging and MR-spectroscopy). Results: VBM showed reduction in primary somatosensory and visual areas (ipsilateral-hemisphere). Functional analysis showed potential neurocompensatory mechanisms and reorganization (left hemisphere). Metabolic data indicated reduced glutamate in the left somatosensory area, and increased N-acetylaspartate in the right somatosensory area. Impact: We phenotyped a mouse model of limb amputation and showed that sensory and motor areas are involved in the manifestation of pain, which strengthens previous evidence and guides future research. |
| 08:39 | 0049.
 | Cross-species comparison: imaging and mapping gastric motor functions in humans and rats using contrast-enhanced rapid MRI Xiaokai Wang1, Fatimah Alkaabi1, Ulrich Scheven2, Minkyu Choi3, Douglas Noll1, and Zhongming Liu4
1Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States, 2Mechanical Engineering, University of Michigan, Ann Arbor, MI, United States, 3Electrical and Computer Engineering, University of Michigan, Ann Arbor, MI, United States, 4Biomedical Engineering, Electrical and Computer Engineering, University of Michigan, Ann Arbor, MI, United States Keywords: Digestive, Digestive, Gastrointestinal, Stomach Motivation: Direct and granular cross-species comparisons of gastric motor functions remain scarce in the literature. Goal(s): This study aims to establish functional similarities and distinctions of the stomach between humans and rats, and lay the foundation for integrating preclinical findings into clinical gastrointestinal studies. Approach: Using comparable MRI protocols, we examined the interspecies parallels and distinctions in their functions as pressure and peristaltic pumps. Results: Similarities were confirmed with high-resolution spatial maps, including intragastric pressure gradient and spatial distribution of peristaltic amplitude and frequency, despite their differences in scale. We highlighted the pronounced variance in initialization and spatial coordination of peristaltic contractions across species.
Impact: This work serves as the first one to map and compare gastric motor events with comparable MRI protocols, laying the foundation for preclinical rat research to clinical translation using contrast-enhanced gastrointestinal MRI. |
| 08:51 | 0050.
 | Impact of Gender on Alzheimer’s disease: a Behavioral and Metabolic Analysis in AβPP-PS1 Mouse Model Akila Ramesh1,2 and Anant Bahadur Patel1,2
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, India, 2Academy of Scientific and Innovative Research, Ghaziabad, India Keywords: Alzheimer's Disease, Metabolism, Neurodegeneration, Alzheimer's disease Motivation: Sex specific status of neurometabolic activity in Alzheimer’s disease is poorly understood. Goal(s): To assess glutamatergic and GABAergic neurometabolism in different brain regions of male and female AβPP-PS1 mouse model of AD. Approach: Tracer approach involving infusion of [1,6-13C2]glucose in AβPP-PS1 mouse model of AD together with 1H-[13C]-NMR spectroscopy was used to estimate rate of neuronal Glucose oxidation (CMRGlc(Ox)) in AD mice. Results: The neuronal metabolic activity reduced in the cerebral cortex, hippocampus and cerebellum of female AβPP-PS1 mice. However, only hippocampal neurometabolic activity was reduced in the male mice. This suggests a differential progression of AD in male and female AβPP-PS1 mice. Impact: The findings of the study suggest differential progression of AD in male and female AβPP-PS1 mice. These factors require attention for future interventions for AD treatment. |
| 09:03 | 0051.
 | Brain metabolic alteration at a late phase of immune fatigue model mice using parahydrogen-polarized [1-13C] pyruvate MRI. Shingo Matsumoto1, Hayate Tomiyama1, and Hiroshi Hirata1
1Information Science and Technology, Hokkaido University, Sapporo, Japan Keywords: Biomarkers, Hyperpolarized MR (Non-Gas) Motivation: Long-lasting brain issues including cognitive impairments after infections have become a worldwide problem after COVID-19. Goal(s): Our goal was to detect brain metabolic alteration at a late phase of immune fatigue. Approach: Parahydrogen-polarized 13C MRI of pyruvate metabolism was applied in the brain of 3 days poly I:C treated mice. Results: Alteration of brain pyruvate metabolism toward glycolysis was observed in both acute phase at day 3 and late phase at day 14 of immune fatigue model mice, which was correlated with diminished dopamine signal marker and nighttime moving distance in open-field test. Impact: Our demonstration of a detectable alteration of brain pyruvate metabolism by parahydrogen-polarized 13C MRI at a late phase of immune fatigue mice can be a useful biomarker of cognitive impairments after infections such as brain fog of long-COVID. |
| 09:15 | 0052.
 | Cell-Specific Mapping of MR Spectroscopic Signatures: A Pilot Study in a Murine Glioma Model Yizun Wang1,2, Urbi Saha3, Marina Milad4, Edward J Roy3,5, Andrew M Smith1,5, and Fan Lam1,2,5,6
1Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 2Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 3Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 4Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 5Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 6Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States Keywords: Spectroscopy, Spectroscopy Motivation: Effective monitoring of tumor progression and therapeutic efficacy should benefit from new in vivo imaging capability to resolve cell-specific contributions at tissue level. Goal(s): To develop a new MRSI-based approach to resolve tumor cell-specific components at individual imaging voxels leveraging the spectral dimensions. Approach: We proposed a multiscale experimental and computational MRSI framework that learns cell-specific spectroscopic signatures from glioma cell lines and resolves intravoxel nontumor and tumor-specific components in vivo using the learned signatures. Results: Results from cellular mixtures and glioma-bearing mice demonstrated the potential of our method. Time-dependent, spatially-resolved tumor cell maps can be obtained, showing tumor growth in vivo. Impact: The proposed approach marks a potential new paradigm to map cellular complexity at tissue level leveraging additional imaging dimensions and machine learning. It holds the promise to provide new tools for tumor grading, progression monitoring and treatment assessment. |
| 09:27 | 0053.
 | Magnetic Resonance Elastography captures tumor invasiveness and therapy response in the invasive S24-glioma model Hannah Elisabeth Fels-Palesandro1,2, Sophie Heuer3,4, Berin Boztepe1,5, Yannik Streibel1, Chenchen Pan3,4, Ina Maria Weidenfeld1,2, Manuel Fischer1, Volker Sturm1, Daniel Dominguez-Azorin3,4, Ralph Sinkus6,7, Amir Abdollahi2,8, Sabine Heiland1, Frank Winkler3,4, Martin Bendszus1, Michael Breckwoldt1,5, and Katharina Schregel1,4
1Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany, 2Clinical Cooperation Unit Translational Radiation Oncology, Deutsches Krebsforschungszentrum, Heidelberg, Germany, 3Neurology, Heidelberg University Hospital, Heidelberg, Germany, 4Clinical Cooperation Unit Neurooncology, Deutsches Krebsforschungszentrum, Heidelberg, Germany, 5Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, Deutsches Krebsforschungszentrum, Heidelberg, Germany, 6School of Biomechanical Engineering and Imaging Science, King's College London, London, United Kingdom, 7INSERM UMRS1148 - Laboratory for Vascular Translational Science, University of Paris, Paris, France, 8Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany Keywords: Elastography, Elastography, Cancer, Neuro Motivation: In a neurooncological setting clinically established MRI-sequences have shortcomings with regards to tumor invasion and therapy-associated parenchyma changes. Goal(s): Our goal was to determine if MRE and the ADC could improve detection of tumor cell invasion and radiotherapy effects. Approach: 23 tumor-bearing mice and 9 sham injected mice underwent MRE- and MRI-scans for up to 16 weeks, a subgroup of animals underwent additional radiotherapy. Results: MRE was sensitive to early tumor invasion and MRE and ADC captured radiotherapy effects so far not detectable with established MRI-sequences. Impact: In a preclinical setting the ADC and especially MRE allow for a better characterization of therapeutic effects and tumor cell invasion and should thus also be evaluated in a clinical setting. |
| 09:39 | 0054.
 | Post-Mortem Changes of Anisotropic Mechanical Properties in the Porcine Brain Assessed by MR Elastography Shuaihu Wang1, Kevin N Eckstein1, Charlotte A Guertler1, Curtis L Johnson2, Ruth J Okamoto1, Matthew DJ McGarry3, and Philip V Bayly1
1Washington University in St. Louis, St. Louis, MO, United States, 2University of Delaware, Newark, DE, United States, 3Dartmouth College, Hanover, NH, United States Keywords: Elastography, Elastography Motivation: Anisotropic mechanical properties of brain tissue define the mechanobiology of injury and disease, but most measurements of direction-dependent properties have been performed post-mortem. Goal(s): To characterize the post-mortem changes Approach: We use magnetic resonance elastography and diffusion tensor imaging with a transversely-isotropic nonlinear inversion algorithm to estimate anisotropic mechanical properties of minipig brain, both in vivo and at specific times after death. Results: White matter is stiffer, more dissipative, and more anisotropic than gray matter when the minipig is alive, but except for tensile anisotropy, these differences largely disappear post-mortem. Overall, brain tissue becomes stiffer, less dissipative, and less mechanically anisotropic after death. Impact: Our demonstration of significantly different mechanical properties in living versus post-mortem minipig brains is critical to improving computational models of TBI and correctly interpreting their predictions, which have relied on post-mortem measurements of brain material properties for several decades. |
| 09:51 | 0055.
 | An optimised framework for relating microstructural MRI to multi-stain histology metrics in the mouse brain Cristiana Tisca1, Mohamed Tachrount1, Adele Smart1, Frederik J Lange1, Amy FD Howard1, Chaoyue Wang1,2, Benjamin Tendler1, Lily Qiu1, Claire Bratley1, Daniel Z L Kor1, Istvan N Huszar1,3, Javier Ballarobre-Barreiro4, Manuel Mayr4, Jason Lerch1,5, Aurea B Martins-Bach1, and Karla L Miller1
1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 2SJTU-Ruijin-UIH Institute for Medical Imaging Technology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 3Athinoula A. Martinos Centre for Biomedical Imaging, Harvard University, Cambridge, MA, United States, 4British Heart Foundation Centre of Research Excellence, King's College London, London, UK, London, United Kingdom, 5Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada Keywords: Biology, Models, Methods, Microstructure, Validation Motivation: Voxel-wise MRI-histology comparisons routinely rely on manual segmentations of ROIs and subjective quantitative histological metrics, an error-prone and labour-intensive process.
Goal(s): We developed an automated framework for investigating relationships between multiple MRI metrics and immunostains.
Approach: We used MRI and histology protocols optimised for ex-vivo mouse brains. We co-registered this data and derived quantitative histological metrics. We conducted voxel-wise correlations in grey and white matter between MRI (diffusion, R2* and susceptibility) and immunohistochemistry (myelin, neurofilament and extracellular matrix proteins).
Results: Our framework successfully recapitulated known relationships for myelin and neurofilaments and, interestingly, demonstrated new relationships between MRI metrics and extracellular matrix protein stains.
Impact:
Our
optimised framework combines openly-shared software and MRI-histology protocols,
addressing current challenges, such as obtaining high-quality histology data, MRI-to-histology
registration and automatic extraction of quantitative histological metrics.
This can benefit future MRI-histology studies in mouse brains prepared for ex-vivo
MRI. |
| 10:03 | 0056.
 | Atlas-based Analysis and Deformation-Based Morphometry of Structural MRI to Study Effects of Hypertension on Rat Brain Structure Haley Elizabeth Wiskoski1,2, Loi Do1, Marc Zempare3, Natalie Carey3, Amy Delmendray3, Kimberly Young3, Kimberly Bohne3, Monica Chawla3, Pradyumna Bharadwaj4, Kenneth Mitchell5, Gene Alexander3,4,6, Carol Barnes3,4, and Theodore Trouard1,3,7
1Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, United States, 2James C. Wyant College of Optical Sciences, The University of Arizona, Tucson, AZ, United States, 3Evelyn F. McKnight Brain Institute, The University of Arizona, Tucson, AZ, United States, 4Department of Psychology, Neurology, and Neuroscience, The University of Arizona, Tucson, AZ, United States, 5Health Sciences Center, Tulane University, New Orleans, LA, United States, 6Division of Neural Systems, Memory, and Aging, The University of Arizona, Tucson, AZ, United States, 7Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States Keywords: Preclinical Image Analysis, Hypertension Motivation: Hypertension (HTN) is a known risk factor for cardiovascular disease and cognitive decline, with a need to understand its effects on brain function and structure using animal models. Goal(s): We aim to investigate impact of HTN on the brain of transgenic Cyp1a1-Ren2 rats through atlas-based and deformation-based analysis of high-resolution structural MRI. Approach: Rats were divided into control and hypertensive groups. Structural MRI was carried out, upon which atlas-based analysis and deformation-based morphometry were performed. Results: Induced HTN significantly affected peripheral organs but showed no significant brain volume changes or cognitive differences. This suggests potential brain protection mechanisms against HTN, warranting further investigation. Impact: This research
explores effects of hypertension on the brain using a rat model and structural MRI. Results show the brain appears resilient to
induced hypertension compared to peripheral organs, highlighting need for investigation into protective mechanisms and their potential
degradation. |