| Computer # |
| 4103.
 | 81 | Histological validation of Quantitative Gradient Recalled Echo (qGRE) MRI as in vivo early neurodegeneration biomarker in Alzheimer’s Disease Michal R Tomaszewski1, Alexander L Sukstansky2, Hyking Haley1, Xiangjun Meng1, Corey O Miller1, and Dmitriy A Yablonskiy2
1Translational Imaging, Merck & Co., Inc., West Point, PA, United States, 2Washington University, St Louis, MO, United States Keywords: Biomarkers, Neurodegeneration Motivation: Robust methods are urgently needed for preclinical evaluation of novel Alzheimer Disease (AD) therapies to accelerate drug discovery. MRI methods hold significant promise, with quantitative Gradient Recalled Echo (qGRE) shown to provide insight into neurodegeneration in AD prior to atrophy development in humans. Goal(s): In this study a novel method is shown to non-invasively measure the longitudinal neuronal loss in the hippocampus of a mouse model of AD. Approach: Histological validation of the findings is performed. Results: A strong correlation is revealed between the MRI metric and myelin content, hence offering the explanation for the mechanism of observed contrast. Impact: A
robust method for longitudinal in-vivo quantification of neuronal density loss
in a mouse model of AD is presented and validated, allowing for efficient
preclinical evaluation of novel AD therapeutics and accelerated drug
development in the field. |
| 4104.
 | 82 | Discrepancy in the distribution of H217O and Gd-DTPA during and after intrathecal infusion in chronic unilateral hypoperfusion model mice. Takayuki Obata1, Manami Takahashi1, Nobuhiro Nitta1, Jeff Kershaw1, Hiroyuki Kameda2, Kohsuke Kudo2, and Hiroyuki Takuwa1
1National Institutes for Quantum Science and Technology, Chiba, Japan, 2Department of Diagnostic and Interventional Radiology, Hokkaido University, Sapporo, Japan Keywords: Neurofluids, Neurofluids Motivation: It is desirable to accurately evaluate water movement within the brain so that it can be compared with neurofluid flow observed with other tracers. Goal(s): The aim of this study was to evaluate the motion of neurofluids in a mouse model of chronic unilateral hypoperfusion using H217O and Gd-DTPA as MRI tracers. Approach: Dynamic T2WI and T1WI were performed during and after intrathecal infusion of H217O and Gd-DTPA, respectively. Results: There was a clear difference in the distributions of H217O and Gd-DTPA after intrathecal injection. This suggests that different mechanisms are involved in the transport of water and other molecules in the brain. Impact: The difference in distribution of the tracers in the UCCAO model suggests that this method may be useful for investigating the pathological mechanism of various brain diseases. |
| 4105.
 | 83 | Application of Synthetic MRI in Neonatal Brain Myelin Development Evaluation Shili Liu1, Zhiqiang Chen2, Shaoru Zhang3, Yunshu Zhou3, Ruodi Zhang3, Xiaohua Chen3, Yuhui Xiong4, and Aijun Wang5
1Clinical medicine school of Ningxia Medical University, YinChuan, China, 2Department of Radiology ,the First Hospital Affiliated to Hainan Medical College, Haikou, China, 3Clinical medicine school of Ningxia Medical University, Yinchuan, China, 4GE Healthcare，MR Reseaich, Beijing, Beijing, China, 5General Hospital of Ningxia Medical University, Yinchuan, China Keywords: fMRI Analysis, Neonatal, Synthetic Magnetic Resonance Imaging,Myelination；Brain；Relaxometry; Development Motivation: Conventional MRI sequences used in clinical practice cannot quantitatively evaluate the development of white matter in newborns. Goal(s): To explore the feasibility and application value of Synthetic MRI (SyMRI) in cerebral white matter myelin development of full-term neonates. Approach: Use intra-group and inter-group comparison of quantitative relaxation metrics obtained by SyMRI to evaluate the white matter myelin development level in newborns of different gestational ages. Results: Quantitative relaxation metrics derived by SyMRI can quantitatively evaluate the formation of myelin and brain maturity in full-term newborns. T1 and T2 values in different regions can reflect the differences in myelin sheath formation time. Impact: SyMRI can be used in clinical practice to investigate the myelin development of white matter in full-term newborns, and provide imaging basis for early detection and diagnosis of neonatal brain developmental dysplasia and disease conditions in newborns. |
| 4106.
 | 84 | The universe is asymmetric, the mouse brain too. Alejandro Rivera-Olvera1, Danielle J. Houwing2,3, Jacob Ellegood4, Shang Masifi3, Stephany L.L. Martina3, Andrew Silberfeld5,6, Olivier Pourquie5,6,7, Jason P. Lerch8,9, Clyde Francks2,3,10, Judith R. Homberg3, Sabrina van Heukelum3, and Joanes Grandjean3,10
1Cognitive Neuroscience, Donders Institute for Brain, Behaviour, and Cognition, Nijmegen, Netherlands, 2Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands, 3Donders Institute for Brain, Behaviour, and Cognition, Nijmegen, Netherlands, 4Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, 5Harvard Medical School, Boston, MA, United States, 6Brigham and Women's Hospital, Boston, MA, United States, 7Harvard University, Cambridge, MA, United States, 8Mouse Imaging Centre, Toronto, ON, Canada, 9Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom, 10Radboud University Medical Center, Nijmegen, Netherlands Keywords: Small Animals, Brain, Asymmetry Motivation: Exploring the mechanistic insights into the development of (altered) brain asymmetry in cognitive and psychiatric conditions requires the use of preclinical models. However, as asymmetry patterns are generally nuanced, even within human populations, substantial sample sizes are required to describe this phenomenon accurately. Goal(s): Our goal was to explore the presence of brain asymmetry in the mouse overcoming the sample size limitations. Approach: We leveraged a dataset encompassing MRI data from over 2000 mice. Results: We found robust brain asymmetry in the mouse, as well as asymmetry patterns that differ from those observed in humans.
Impact: The mouse brain is asymmetric and there are some similarities between humans and mice, but species-specific asymmetry patterns need to be taken into account for translational research, reevaluating traditional assumptions and exploring the complexities of brain function across species. |
| 4107.
 | 85 | Diffusion Tensor Imaging Along the Perivascular Space Index in Idiopathic Intracranial Hypertension Alan Finkelstein1, Derrek Schartz2, Giovanni Schifitto2,3,4, and Jianhui Zhong1,2,5
1Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States, 2Department of Imaging Sciences, University of Rochester, Rochester, NY, United States, 3Department of Neurology, University of Rochester, Rochester, NY, United States, 4Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, United States, 5Department of Physics and Astronomy, University of Rochester, Rochester, NY, United States Keywords: Biomarkers, Diffusion/other diffusion imaging techniques, Idiopathic Intracranial Hypertension, DTI-ALPS Motivation: Idiopathic intracranial hypertension (IIH) is caused by elevated intracranial pressure of unknown etiology. In recent years, growing evidence has suggested that impaired glymphatic clearance may mediate IIH pathogenesis. Goal(s): We hypothesized that individuals with IIH would exhibit impaired glymphatic outflow, which could be directly measured using diffusion tensor imaging along the perivascular space (DTI-ALPS). Approach: This work used DTI-ALPS to investigate glymphatic clearance in individuals with IIH, and its association with symptom severity and comorbidities. Results: Impaired glymphatic clearance was directly related to the clinical severity of IIH, as suggested by a lower DTI-ALPS index. Impact: We employed perivascular diffusion tensor imaging to study glymphatic flow in IIH patients. Lower ALPS index correlated with greater clinical severity, offering insights into IIH's pathomechanism and its potential for diagnosis and treatment evaluation. |
| 4108.
 | 86 | Susceptibility tensor imaging of ex vivo human hemibrain using 7T human MR scanner Yuto Uchida1, Hyeong-Geol Shin2, Javier Redding-Ochoa3, Kengo Onda1, Alexander Barrett3, Adnan Bibic1,2, Juan C. Troncoso3, Peter van Zijl1,2, Kenichi Oishi1,4, and Xu Li1,2
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Department of Pathology, Johns Hopkins University, Baltimore, MD, United States, 4The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Baltimore, MD, United States Keywords: Preclinical Image Analysis, Microstructure Motivation: High-resolution ex vivo susceptibility tensor imaging (STI) shows promise in visualizing detailed microstructural neuroanatomy related to tissue magnetic susceptibility contrast but is usually challenging with large human brain samples. Goal(s): This work aimed to demonstrate a feasible protocol for STI on postmortem human hemibrain using a 7T human MR scanner. Approach: De-identified human brain samples of the left hemisphere were collected, prepared, and scanned with a 3D multi-echo gradient echo sequence with 0.5 mm isotropic resolution. Results: Multi-orientation quantitative susceptibility mapping and STI with a maximum of 12 orientations were obtained. Myelinated fibers and iron deposition in cortical substructures were visualized. Impact: The proposed ex vivo MRI protocol is expected to be helpful to researchers
interested in STI. The ex vivo STI acquired through this protocol may provide
anatomical references for in vivo STI studies. |
| 4109.
 | 87 | Modeling structural and functional connectomics with proteomics in a preclinical model of tauopathy Elizabeth Hipskind1, Lindsay Fadel1, Caitlyn Ortiz2, Katherine Nelson2, Steen Pedersen2, Md. Abul Hassan Samee2, and Robia Pautler2
1Neuroscience, Baylor College of Medicine, Houston, TX, United States, 2Integrative Physiology, Baylor College of Medicine, Houston, TX, United States Keywords: Small Animals, Alzheimer's Disease, resting state fMRI, functional connectivity, tau Motivation: Identifying neurological changes in Alzheimer’s Disease (AD) is critical for early intervention. Tau accumulation is a key pathological feature in AD and other neurodegenerative diseases. Goal(s): This project investigates how tau accumulation impacts structural and functional connectivity in the brain and cognitive decline. Approach: We use behavioral assessments of learning and memory in the rTg4510 mouse model of tauopathy with awake resting-state fMRI and diffusion tensor imaging at three timepoints during the course of tau accumulation. Results: As tau accumulates, we identify patterns of functional connectivity changes. We plan to use machine learning to link these changes to cognitive decline. Impact: We study how tau accumulation affects brain functional
connectivity and cognitive decline in a mouse model of tauopathy. Magnetic
resonance imaging may offer non-invasive tools for assessing Alzheimer's
Disease pathology, potentially aiding in early diagnosis. |
| 4110.
 | 88 | Correlation between intra-axonal T2 and histological axon diameter in rat brain Veronica P Dell'Acqua1, Greg D Parker1, Chantal M W Tax1,2, Ruth Hughes3, Tom O'Sullivan4, Martin Fuller4, Michelle Peckham5, Erick Jorge Canales Rodriguez6, Jurgen E Schneider7, Irvin Teh7, and Derek K Jones1
1Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, United Kingdom, 2Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 3Bioimaging and Flow Cytometry Facility, University of Leeds, Leeds, United Kingdom, 4Astbury CryoEM facility, Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom, 5University of Leeds Astbury Centre for Structural Molecular Biology and the School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom, 6Signal Processing Laboratory 5 (LTS5), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 7Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom Keywords: Biology, Models, Methods, Validation, Axon Diameter, Diffusion-Relaxation, Relaxometry, data analysis Motivation: Alteration of the axon radii has been previously linked with neurodevelopmental disorders and neurologic pathologies. The possibility of resolving submicrometric axon diameter yields the potential to open new diagnostic avenues. Goal(s): Validation of the previously presented surface-based relaxation model, assessing the feasibility of estimating axon diameter based on intra-axonal transverse relaxation times. Approach: Correlating diffusion-relaxation MRI data acquired in an ex-vivo rat sample and axon diameter measures based on histology data in the Corpus Callosum. Results: The results confirm the previously reported linear relationship between intra-axonal T2 and axon diameter as estimated based on histology. Impact: This first direct validation experiment of the relationship between intra-axonal T2 and axon diameter employing a surface-based relaxation model could pave the way for a novel biomarker in neurological disease. |
| 4111.
 | 89 | Modeling Behavior, Functional Connectomics, and Proteomics in a Mouse Model of Alzheimer’s Disease Lindsay Fadel1, Elizabeth Hipskind1, Caitlyn Ortiz2, Katherine Nelson2, Steen Pedersen2, Md. Abul Hassan Samee2, and Robia Pautler2
1Neuroscience, BAYLOR COLLEGE OF MEDICINE, Houston, TX, United States, 2Integrative Physiology, BAYLOR COLLEGE OF MEDICINE, Houston, TX, United States Keywords: Small Animals, Alzheimer's Disease, resting state fMRI, Functional Connectivity, Spatial Proteomics Motivation: Alzheimer's Disease (AD) is a devastating neurodegenerative disease that affects 50 million people worldwide. Goal(s): Advancements in neuroimaging techniques that can detect deficits prior to significant accumulation of pathology and cognitive decline would aid in early detection, diagnosis, and possible therapeutic intervention. Approach: Resting state fMRI studies have identified early functional connectivity (FC) deficits in memory-related brain regions, preceding cognitive impairment, making it a promising clinical marker for AD. Results: Using an AD mouse model, our study has identified unique patterns of FC changes across disease progression. Using machine learning we are working to establish relationships between neuroimaging and cognitive and proteomic changes. Impact: This study aims to uncover dynamic alterations in functional connectivity and the link to cognitive and proteomic changes using a mouse model of Alzheimer's Disease. These findings offer potential insights for early detection and diagnostic advancements in Alzheimer's Disease research. |
| 4112.
 | 90 | Delayed CSF clearance may provide a more sensitive disease marker than blood-CSF-barrier impairment in an Alzheimer’s disease mouse model Yuhan Bian1,2,3, Hannah Fuehrer4, Di Cao1,2,3, Yuanqi Sun1,2,3, Chunming Gu1,2,3, Yinghao Li1,2,3, Adnan Bibic2, Yuguo Li2, Jiangyang Zhang5, Linda Knutsson2,3,6, Peter C.M. Van Zijl1,2,3, Wanli Smith4, and Jun Hua2,3
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Neurosection, Division of MRI Research, Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States, 5Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United States, 6Department of Neurology, Johns Hopkins University, Baltimore, MD, United States Keywords: Neurofluids, DSC & DCE Perfusion, Alzheimer' Disease; CSF clearance; GBCA Motivation: Accumulation of abnormal proteins in AD has been linked with barrier breakdown between blood and tissue or CSF, and impaired clearance from the brain. Goal(s): To use GBCA-induced signal changes in ventricular CSF following intravenous injection and its decay over time as indices to study the integrity of blood-CSF barrier (BCSFB) and GBCA clearance via CSF, respectively. Approach: Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed in the 3xTg-AD mouse model. Results: Impaired clearance in AD mice became significant at 8 months. The amount of GBCA crossing BCSFB appeared similar between AD and WT mice at these early stages. Impact: Our results suggest that delayed CSF clearance may provide a more sensitive marker for AD, and parameters measured during the clearance phase may be more robust than measures obtained immediately after GBCA administration. |
| 4113.
 | 91 | Progressive brain volume alterations in the zQ175DN mouse model of Huntington’s Disease using in vivo MRI Nicholas Vidas-Guscic1,2, Tamara Vasilkovska1,2, Stefanie Pluym1, Joëlle van Rijswijk1,2, Johan Van Audekerke1,2, Haiying Tang3, Roger Cachope3, Dorian Pustina3, Annemie Van der Linden1, Daniele Bertoglio1,2, and Marleen Verhoye1,2
1Bio-Imaging Lab, University of Antwerp, Wilrijk, Belgium, 2µNeuro Center for Excellence, University of Antwerp, Wilrijk, Belgium, 3CHDI Foundation Inc, Princeton, NJ, United States Keywords: Small Animals, Genetic Diseases, Volumetric Motivation: Robust translational imaging biomarkers are needed to facilitate the development of disease-modifying treatments for Huntington’s disease (HD), a rare inherited neurodegenerative disease. Goal(s): To determine the use of structural atrophy determined with MRI as a robust translational biomarker for testing therapeutics in mouse models prior to people with HD. Approach: In this work, we used semi-automatic delineations and tensor-based morphometry (TBM) of 3D high-resolution anatomical MR images to assess structural anomalies in the knock-in zQ175DN model of HD at different ages. Results: We detected progressive volumetric decrease in the zQ175DN mouse model, offering a powerful translational biomarker for the assessment of disease-modifying therapies. Impact: We report the first brain-wide structural study of zQ175DN mice using in vivo MRI. Our work supports structural atrophy as a robust translational biomarker for testing therapeutics in mouse models prior to people with HD. |
| 4114.
 | 92 | The impact of high-fat, obesogenic diets on brain volume in a commercially available mouse model of fatty liver disease. Sui-Seng Tee1, Li Jiang1, and Salaheldeen Elsaid1
1University of Maryland School of Medicine, Baltimore, MD, United States Keywords: Small Animals, Metabolism Motivation: Large-scale brain imaging studies have shown a significant association between altered brain structure in obesity. However, the exact biological processes remain elusive. Here, we use inbred mice, fed diets with pre-determined caloric contributions to elucidate diet-specific contributions to brain structure alterations in obesity. Goal(s): The goal of this study is to perform morphometric analysis of the brains of a commercially available mouse model of obesity. Approach: Mice were fed regular (5% fat), or obesogenic diets (40% fat). After 8 weeks all mice were scanned using MRI. Results: Obese mice show volume reduction, but not statistically significant. Neocortical volumes were larger in obese mice. Impact: The use of commercially available, diet-induced, obese mouse models provides an opportunity for the neuroimaging community to produce consistent structural and functional to support the assertion that obesity may be a ‘brain disease’. |
| 4115.
 | 93 | Assessment of disease progression in the zQ175 Heterozygous Huntington’s mouse model Florian Schmid1, Graham Ruby1, and Johannes Riegler1
1Calico Life Sciences, South San Francisco, CA, United States Keywords: Biology, Models, Methods, Translational Studies, Huntington's Motivation: Suitable mouse models of Huntington's disease are crucial for the evaluation and translation of potential new treatments. Goal(s): We studied the zQ175 heterozygous model for Huntington's disease in comparison to wildtype controls. Approach: We compared brain MRI and behavioral readouts over a large part of the lifespan to characterize and quantify phenotypes. Results: The model only developed a mild brain atrophy phenotype, part of the size difference was shown to be due to reduced growth rather than atrophy. Impact: This study can help researchers to make better informed decisions on mouse model selection for evaluation of potential treatment efficacy in translational studies of Huntington's disease. |
| 4116.
 | 94 | DTI and NODDI to monitor treatment effect for stroke in middle cerebral artery occlusion mouse model Donghoon Lee1, Todd Richards1, Van Pham1, Stephanie Totten1, Brendan Schweitzer1, and Jonathan Weinstein1
1University of Washington, Seattle, WA, United States Keywords: Small Animals, Stroke Motivation: Stroke is a serious medical condition that can lead to long-term disability and death, yet has limited treatment options. Goal(s): This study aims to identify effective diffusion MRI biomarkers in monitoring treatment response with a repurposed drug for stroke. Approach: In vivo diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) were performed on the mouse brain with middle cerebral artery occlusion (MCAO). Mice were imaged on the 14T MR system on day 7 post-MCAO, following a 7-day treatment regimen with either Senicapoc or vehicle. Results: Certain DTI and NODDI parameters were found to demonstrate strong treatment effect. Impact: Both DTI and NODDI maps may provide useful
information in monitoring response to repurposed Senicapoc drug treatment for
stroke. |
| 4117.
 | 95 | Predicting Pain caused by the Intervertebral Disc Degeneration in Large Animal Model Using CEST MRI Data Karandeep S Cheema1,2, Chushu Shen1,2, Dante Rigo De Righi2, Wafa Tawackoli2, Yibin Xie2, Candace Floyd3, Dmitriy Sheyn4, and Debiao Li1,2
1Bioengineering, University of California, Los Angeles (UCLA), Los Angeles, CA, United States, 2Biomedical Imaging Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, United States, 3Emergency Medicine, Emory University, Atlanta, GA, United States, 4Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA, United States Keywords: Biomarkers, CEST & MT Motivation: Use MRI CEST data to predict lower back pain scores in porcine model. Goal(s): To use a porcine model to correlate MRI-based biomarkers with backpain associated with IVD degeneration. Approach: IVD injury was induced in the lower three lumbar discs while keeping the upper two intact. MRI scans were performed every 4 weeks upto 16 weeks post injury. Pearson Correlations were used for data analysis. Results: MTR and Exchange rate signal clearly separate the injured and the healthy disks. There is a positive correlation between higher exchange rate signal and higher back pain while a negative correlation between MTR and pain scores. Impact: The study bridges the gap between small animal models and
human clinical studies by employing a clinically relevant large animal
model. The development of MRI-based pain assessment biomarkers is
a critical step toward advancing our understanding of lower back
pain. |
| 4118.
 | 96 | Characterization of atlas based volumetric changes in unilateral 6-OHDA-induced Parkinson’s rat model Bharti Rana1, Sadhana Kumari2, S Senthil Kumaran2, Suman Jain3, and Shefali Chaudhary4
1Department of Computer Science, University of Delhi, Delhi, India, 2Department of NMR, All India Institute of Medical Sciences, New Delhi, India, 3Department of Physiology, All India Institute of Medical Sciences, New Delhi, India, 4Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States Keywords: Preclinical Image Analysis, Segmentation, Parcellation, atlas based volume extraction Motivation: Manual characterization of brain regions is studied without prior knowledge to identify changes in GM/WM volume in PD. Goal(s): Characterisation of GM and WM changes in 6-OHDA PD model as compared to sham control Approach: Parcellated the rat brain into predefined regions using a rat atlas and performed the Wilcoxon rank signed rank test to identify significant changes in GM/WM volume. Results: Significant loss in GM volume of a few brain regions in PD and Sham observed in 3rd and 7th week. Increase in WM volume for 3rd week is observed. Impact: We identified GM loss and WM gain in a few brain regions without manual intervention which helps in understanding the structural changes in the whole brain in PD and Sham. |