| Computer # |
| 4024.
 | 1 | Functional and structural connectivity changes in neocortical regions of the brain in a mouse model of Alzheimer’s disease Ziyi Wang1, Hui Li1, Bowen Shi1, Qikai Qin1, Qiong Ye2, and Garth John Thompson1
1iHuman institute, ShanghaiTech University, Shanghai, China, 2High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Shanghai, China Keywords: Alzheimer's Disease, Alzheimer's Disease, fMRI; DTI; brain function and structure Motivation: The early diagosis of Alzheimer's disease clinically using non-invasive techniques is important, find the relationship of brain structural and functional connectivity will helpful to diagnosing. Goal(s): We used multimodal MRI technique to elucidate the differences between different ages of AD and WT mice and analyze the relationship between brain structure and brain function. Approach: We used rs-fMRI to measure the functional connectivity, used DTI to measure the microstructure and structural connectivity of the brain. Results: Our results showed higher structural connectivity causes higher functional connectivity, but in gustatory region, the functional connectivity had a negative correlation with structure. Impact: Early diagnose is the important part to delay the progression of AD, the relationship of structural and functional connectivity is helpful to drug discovery. Our results suggest several potential early
biomarkers for study in young versus old, humans and mice. |
| 4025.
 | 2 | Comprehensive Assessment of Age-Related Hippocampal Changes in Murine Models Through Multimodal MRI and Spectroscopy Zhonghui Qie1, Yanting Yang1, Scott A. Small2,3, and Jia Guo1,4
1Zuckerman Institute, Columbia University, New York, NY, United States, 2Department of Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United States, 3Department of Neurology, Columbia University, New York, NY, United States, 4Department of Psychiatry, Columbia University, New York, NY, United States Keywords: Aging, Aging, hippocampus, CBV, TBM, glutamate, semi-LASER Motivation: Analyzing aging mice and controls reveals insights into structural, functional, and neurochemical alterations linked to cognitive decline, and offers potential therapeutic leads.
Goal(s): To comprehensively analyze age-related alterations in the hippocampus of mice with MRI, and to elucidate the underlying mechanisms of aging.
Approach: We utilized a multimodality MRI protocol to investigate age-related changes in the mouse hippocampus. Aging mice and a control group were compared.
Results: Structural MRI revealed a significant reduction in hippocampal size in the aging mice. Cerebral blood volume (CBV) MRI showed reduced CBV, indicating hypometabolism. Proton MRS identified significant glutamate (GLU) reductions, suggesting neuronal function alterations.
Impact: Our study of age-related hippocampal changes in mice, revealing reduced hippocampal volume, metabolism and GLU levels. This translational multimodality approach enhances understanding of age-related deficits in the hippocampus, and promotes potential therapies interventions for both preclinical and human studies. |
| 4026.
 | 3 | Cerebral hemodynamics in the ageing marmoset monkeys using ECG-synchronized PCMRI. Caroline Fonta1, Germain Arribarat2, Murial Mescam1, Olivier Balédent3, and Franck Desmoulin2
1CerCo, CNRS-Toulouse University, Toulouse, France, 2U1214 ToNIC, Inserm-Toulouse University, Toulouse, France, 3Image Processing, Hospital University Center of Amiens-Picardie, Amiens, France Keywords: Neurofluids, Aging Motivation: Some cerebrovascular function alterations and cognitive changes are related to ageing. We investigated this issue in marmoset monkeys, offering human-like physiological models. Goal(s): We aimed at describing age-related changes in brain hemodynamics and their potential interest as early markers of normal/pathological ageing. Approach: We analyzed blood flow in intracranial arteries and sinuses by using ECG-synchronized PCMRI. Results: The arterial (basilar trunk and carotids) inflow and venous (inferior and superior sinuses ) outflow sequence is earlier and shorter along the cardiac cycle in old versus young adult marmoset brains. Consequently, neurofluid oscillations appear different during the cardiac cycle as a function of age. Impact: Our study highlights the importance of nonhuman primate models in studying age-related cerebrovascular changes, offering insights into the link between vascular health, brain ageing, and cognitive decline, with implications for early neurodegenerative diseases. |
| 4027.
 | 4 | A Comparative Study of DTI and SANDI for Discriminating Alzheimer's Pathology in a 5xFAD Mouse Model Zhuoheng Liu1, Adrienne Gaughan2, and Nian Wang1
1Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, United States, 2Indiana University School of Medicine, Indianapolis, IN, United States Keywords: Alzheimer's Disease, Alzheimer's Disease, DTI, SANDI Motivation: This study aims to assess DTI and SANDI's ability to detect Alzheimer's disease (AD) in a 5xFAD mouse model. Goal(s): Employ logistic regression and ROC curve analysis on data from 166 brain regions to compare the performance of DTI and SANDI. Approach: Data collection from 5xFAD mice, brain region segmentation, logistic regression modeling, and ROC curve generation. Results: SANDI exhibits superior AD detection capabilities compared to DTI, as evidenced by a higher AUC value, indicating enhanced sensitivity and specificity. These findings highlight SANDI's potential for nuanced preclinical AD biomarkers. Impact: Implementing SANDI over DTI may improve early detection of
Alzheimer's, potentially leading to better patient outcomes through earlier
intervention and more targeted therapeutic strategies in preclinical settings. |
| 4028.
 | 5 | Examining the changes of default-mode network in the developmental brain of transgenic monkeys with Huntington’s disease using rsfMRI Chun-Xia Li1 and Xiaodong Zhang1
1EPC Imaging Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United States Keywords: Other Neurodegeneration, Genetic Diseases, monkey Motivation: The dysfunction of the default-mode network (DMN) in Huntington Disease (HD) patients has been reported in previous studies, but the results remain inconclusive. Goal(s): This study aimed to investigate the dysfunction of the DMN during the evolution of the disease using a transgenic monkey model. Approach: Four HD and 4 age-matched wild-type monkeys were utilized and functional connectivity (FC) data at 3, 4 and 5 years of age were analyzed. Results: Decreased FC in posterior cingulate cortex (PCC) - PCC and increased FC in anterior cingulate cortex (ACC) - PCC in HD monkeys were observed. Impact: The
findings suggest divergent FC alteration patterns in different DMN area exist
concurrently with the evolution of the disease, and the monkey models could
provide a unique platform for preclinical studies of dysfunctionality and
cognitive decline in HD. |
| 4029.
 | 6 | Longitudinal T2 MRI and spectroscopy are sensitive to neuronal damage in an inducible TDP-43 mouse model of ALS Rohan S Virgincar1, Stephen Vito2, Man Kin Choy1, Becca Leahey2, William J Meilandt2, and Luke Xie1
1Translational Imaging, Genentech, South San Francisco, CA, United States, 2Neuroscience, Genentech, South San Francisco, CA, United States Keywords: Other Neurodegeneration, Neurodegeneration, ALS Motivation: MRI is commonly used to monitor different neuropathologies, but has not been widely used for ALS research. Goal(s): We sought to investigate the utility of longitudinal MRI and MRS to assess the course of disease progression in an inducible TDP-43 mouse model of ALS Approach: T2, volume and NAA/tCr (N-acetyl aspartate/total creatine) were measured longitudinally in disease-relevant regions. Results: These metrics significantly changed in the 6-week induction phase of the model and reversed in the 6-week recovery phase, which was consistent with Amino-Cupric-Silver staining for degenerating neurons. NAA/tCr exhibited the greatest change: −29±14% at peak disease. Impact: We have demonstrated that T2 mapping, volumetric MRI, and MRS are sensitive to neuronal damage in a mouse model of ALS. These non-invasive endpoints therefore have the potential to be used clinically to monitor ALS progression and therapeutic efficacy. |
| 4030.
 | 7 | Probing alterations of brain microstructure in 3xTg-AD mouse via water and metabolites diffusion time-dependence Ke Zhou1, Ziyan Wang2, Jiaqiang Zhou3, Chunli Cai4, Yi-Cheng Hsu5, and Min wang1,3
1College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China, 2MR Research&Development Digital, Siemens Shenzhen Magnetic Resonance Ltd, Shenzhen, China, 3Department of Endocrinology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China, 4Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China, 5MR Collaboration, Siemens Healthcare Ltd, Shanghai, China Keywords: Alzheimer's Disease, Diffusion/other diffusion imaging techniques, DW-MRS Motivation: Diffusion-weighted MR Spectroscopy(DW-MRS) gives access to diffusion properties of endogenous intracellular metabolites to characterize brain cell microstructureµenvironment, which could potentially reflect changes in neuropathology during early Alzheimer's disease(AD). Goal(s): To measure the time-dependent diffusion and kurtosis of the intracellular metabolites and water in the 3xTg-AD mouse. Approach: In-vivo DW-MRS was applied to measure the hippocampus location at different diffusion-times(Td) in four 3xTg mice and four wild-type-C57BL/6 mice(200-day-old/females). Results: The intracellular metabolites change distinctly compared to water in Td-dependency and restricted diffusion between AD and control group. The Kurtosis of metabolites increased significantly in early-AD while water diffusion showed no difference between 2 groups. Impact: This work provides a unique insight into the diffusion time-dependency and kurtosis measurements of intracellular metabolites and water to probe the microstructural changes during the early presymptomatic stages of AD, which helps revealing some underlying processes during AD pathogenesis. |
| 4031.
 | 8 | In Vivo Assessment of Cerebral β-Hydroxybutyrate Metabolism in APPNL-F/NL-F Mouse Model of Alzheimer's Disease using 2H MR Spectroscopy Narayan Datt Soni1, Anshuman Swain1, Paul Jacobs1, Halvor Juul1, and Ravinder Reddy1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States Keywords: Alzheimer's Disease, Deuterium, 2H-MRS, Brain, Alzheimer's disease, Metabolism Motivation: Among all, glucose hypometabolism is a characteristic pathology in Alzheimer’s disease (AD), under such conditions β-Hydroxy butyrate (BHB) can serve as an alternate source of energy. Measurement of BHB metabolism using a sensitive method could serve as a method for early diagnosis of AD. Goal(s): To monitor BHB metabolism in APPNL-F/NL-F mice. Approach: Monitoring cerebral 2H2-Glx labeling in mice following subcutaneous administration of 2H4-BHB using pulse-acquired 2H-MRS. Results: Although rate of cerebral 2H4-BHB uptake was similar in wild type (WT) and AD mice, moderately enhanced labeling of 2H2-Glx was observed in AD mice compared to WT indicates relatively efficient BHB metabolism in AD. Impact: Although BHB metabolism has been monitored in human and rodent brains
using PET and 13C-MRS, inherent limitations restrict their clinical
translation. Using a safe and sensitive method like 2H-MRS could be
helpful in studying BHB metabolism in various neurodegenerative diseases. |
| 4032.
 | 9 | Novel regional biomarkers of progressive brain degeneration in the TauPS2APP mouse model of Alzheimer’s Disease Man Kin Choy1, William J Meilandt2, Kai Barck1, Vineela D Gandham1, Rohan S Virgincar1, Jose Imperio2, Steve Vito2, Tiffany Wu2, Ainhoa Echeverria2, Chris Bohlen2, Robby M Weimer1, and Luke Xie1
1Translational Imaging, Genentech, South San Francisco, CA, United States, 2Neuroscience, Genentech, South San Francisco, CA, United States Keywords: Alzheimer's Disease, Alzheimer's Disease Motivation: The TauPS2APP mouse is a well-established model of Alzheimer’s Disease. Traditionally, analyses focus on hippocampus and isocortex, but brain-wide analysis may yield a more comprehensive description of brain degeneration and identify additional regional biomarkers.
Goal(s): Identifying robust signatures of brain degeneration resulting from amyloidosis and tauopathy Approach: We conducted a brain-wide voxel-based analysis of longitudinal MRI data from TauPS2APP mice collected from three studies (n=123).
Results: We found expected and persistent hippocampal and isocortical volume differences between wildtype and TauPS2APP mice. Also, we identified progressive atrophy in caudoputamen (95% of 123 TauPS2APP mice) and expansion in subiculum/hippocampal commissures (89% of 123 mice).
Impact: We identified novel and robust regional biomarkers of progressive brain degeneration in the TauPS2APP mouse model of AD. These regions are additional targets for assessing brain degeneration associated with amyloidosis and tauopathy, and for testing new therapies. |
| 4033.
 | 10 | Correlations between alterations in resting-state functional dynamics and memory impairments in the TgF344-AD rat model of Alzheimer’s Disease Sam de Waegenaere1,2, Alya Al-Awlaqi1,2, Lori Berckmans1,2, Marleen Verhoye1,2, and Mohit H Adhikari1,2
1Bio-Imaging Lab, Biomedical Sciences, University of Antwerp, Antwerp, Belgium, 2µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium Keywords: Alzheimer's Disease, Alzheimer's Disease Motivation: Resting-state fMRI studies of Alzheimer’s disease impact on brain’s function commonly use functional connectivity (FC) ignoring sensitive and dynamic readouts such as the co-activation patterns (CAPs) occurring at short timescales. Goal(s): We aimed to assess changes in CAPs, in addition to network-level FC, in a transgenic rat model of Alzheimer’s disease longitudinally. Approach: We acquired high temporal resolution resting-state fMRI and performed FC and CAP analysis. Results: We found increased lateral cortical network FC that correlated with memory impairments at the plaque stage, and hyper and hypoactivation of the default-mode-like-network and hippocampal regions in two CAPs at the pre-plaque and plaque stages respectively. Impact: Our
findings demonstrate that metrics of brain dysfunction of Alzheimer’s disease derived
from high temporal resolution resting-state fMRI not only explain behavioural
manifestations but also capture alterations preceding plaque formation further
validating their translational potential as an early, functional biomarker. |
| 4034.
 | 11 | Using Amide Proton Transfer Imaging to Detect Alzheimer’s Disease Pathology in Mouse Models Jingpu Wu1,2, Jieru Wan3, Yunfan Zou2,4, Chongjun Yang5, Puyang Wang2, Dapeng Liu2, Xiaoning Han3, Shanshan Jiang2, and Jinyuan Zhou2
1Department of Electrical and Computer Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, United States, 2Department of Radiology, School of Medicine, Johns Hopkins University, Baltimore, MD, United States, 3Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States, 4Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, United States, 5Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, United States Keywords: Alzheimer's Disease, CEST & MT, Alzheimer's Disease Motivation: APTw imaging can detect abnormal proteins associated with AD, but the APT signal is confounded by the NOE signal, which affects the diagnostic performance. Goal(s): We want to separate APT and NOE signals and see if the clean signals are better biomarkers for AD diagnosis than APTw signal. Approach: EMR fitting was performed voxel-wise. Group-based analysis of fitted APT#, NOE# and APTw signal values was performed inside cortex and hippocampus. Results: APT# and NOE# provide better contrast than APTw for AD diagnosis. The impact of NOE may explain the discrepancy between animal and human studies for AD. Impact: The fitted APT#
and NOE# signals provide better diagnostic values for AD compared to
traditional APTw imaging. The impact of NOE may explain the discrepancy between
animal and human studies for AD and is worthy of further study. |
| 4035.
 | 12 | Imaging cerebrovascular structure and function in the transgenic mouse model of Alzheimer’s disease Hansol Lee1, Sophia Mirrione1, Nancy E. Ruiz Uribe2, Susie Y. Huang1, Rachel E. Bennett2, and Yi-Fen Yen1
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2Department of Neurology, Massachusetts General Hospital, Charlestown, MA, United States Keywords: Alzheimer's Disease, Blood vessels Motivation: Our previous study in humans found changes in vascular structure in AD/MCI patients but its time course and relationship to AD pathology were unknown. Goal(s): The aim of this study was to assess alterations in the structure and function of blood vessels in transgenic mouse models of AD. Approach: Litters with all four genotypes (wild-type, Aβ only, tau only, and Aβ+tau) underwent perfusion MRI and vessel size imaging as part of a longitudinal study. Results: The vessel size correlates significantly with cerebral blood volume and blood flow in the hippocampus. No group difference was found at the baseline pre-symptom stage. Impact: Success in this study, in conjunction with ex-vivo microscopy, will enhance
our ability to interpret in vivo vascular imaging in people and enable
us to identify individuals for vasculature-targeted therapies and evaluate how
interventions may ameliorate vascular health in AD. |
| 4036.
 | 13 | Exploring the Effects of Phospholipase A2 Inhibition on Brain Metabolism and Pathology in a Rat Model of Alzheimer’s Disease Emily Hiles1,2, Ved Hatolkar2, Colleen Bailey2, Wendy Oakden2, Tina Beckett2, Mary Brown2, JoAnne McLaurin2,3, and Jamie Near1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, 2Sunnybrook Research Institute, Toronto, ON, Canada, 3Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Keywords: Alzheimer's Disease, Spectroscopy Motivation: Current AD treatments do not improve cognitive deficits. Gaining a deeper understanding of the mechanisms underlying AD may reveal new therapeutic targets. Goal(s): Previous work demonstrated elevated choline levels in a preclinical model which may implicate the PLA2 pathway in AD. We aim to explore the role of PLA2 in AD. Approach: To understand the role of PLA2 in AD, we pharmacologically inhibited PLA2 in a preclinical model of AD. Metabolic, behavioural, and pathological aspects of AD were then explored using MRS, Barnes maze, immunostaining, and RNA sequencing. Results: Preliminary data indicate PLA2 inhibition reduces choline levels and improves long-term memory formation. Impact: This work may reveal PLA2 as new therapeutic target that improves cognitive deficits in Alzheimer’s disease. By linking behaviour, pathology, and metabolic processes, this study will give a well-rounded picture of how PLA2 activity impacts AD progression. |
| 4037.
 | 14 | Correlations of Blood and Brain NMR Metabolomics with Mouse Models of Alzheimer’s Disease Franz Knörnschild1, Ella Zhang1, Marta Kobus1, Jiashang Chen1, Jonathan X. Zhou1, Joseph Sun1, Xiaoyu Wang1, Wei Li2, Isabella H. Muti1, Piet Habbel3, Johannes Nowak4,5, Zhongcong Xie2, Yiying Zhang2, and Leo L. Cheng1
1Radiology and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, 2Anesthesia, Massachusetts General Hospital, Boston, MA, United States, 3Charité – Universitätsmedizin Berlin, Berlin, Germany, 4Radiology Gotha, SRH Poliklinik Gera GmbH, Gotha, Germany, 5SRH University of Applied Health Sciences, Gera, Germany Keywords: Alzheimer's Disease, Spectroscopy, Metabolomics, metabolomic imaging, nuclear magnetic resonance, neurodegeneration, small animals Motivation: Alzheimer’s disease (AD) diagnosis currently relies on clinical evaluation, and definitive disease characterization can only be accomplished from tissue pathology during autopsy. Goal(s): Evaluations of AD metabolomics using nuclear magnetic resonance (NMR) spectroscopy to identify potential biomarkers that can differentiate AD from non-AD conditions. Approach: We collected cortex, hippocampus, and blood samples from mice with and without AD, followed by NMR analysis. Results: NMR could differentiate between AD and wild-type (WT) conditions for all tissue types, and metabolomic differences in several spectral regions were observed across disease conditions, leading to the identification of potential contributing metabolites and metabolic pathways. Impact: HRMAS NMR-based metabolomic evaluations can
differentiate mice with and without Alzheimer’s disease (AD), characterize
metabolic states within brain and blood samples, and identify possible AD
biomarkers. It has potential for in vivo implementation and may improve AD
diagnosis in clinic. |
| 4038.
 | 15 | Sex Specific changes in Glutamate and Other Neurometabolites in a Mouse Model of Alzheimer’s Disease: A GluCEST MRI and 1H-MRS Study Narayan Datt Soni1, Anshuman Swain1, Angele Oye-Mba1, Halvor Juul1, Ravi Prakash Reddy Nanga1, and Ravinder Reddy1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States Keywords: Alzheimer's Disease, Alzheimer's Disease, Glutamate, GluCEST, 1H-MRS Motivation: It is well known that prevalence and progression of Alzheimer’s disease (AD), is different across two sexes. Glutamate regulates various cognitive functions including learning and memory and is known to be perturbed in AD though sex specific in vivo studies are limited. Goal(s): To monitor sex-specific changes in cerebral glutamate and other neurometabolites in APPNL-F/NL-F and WT mice. Approach: Glutamate weighted Chemical Exchange Saturation Transfer (GluCEST) MRI and localized 1H-MRS. Results: Significant neurometabolite alterations in the hippocampus of male AD mice were observed, while females remained unaffected. This could be broadly attributed to neuroprotective effects of female reproductive hormones e.g., estrogen. Impact: Although the sex bias in AD pathology has been long known, the actual mechanism
remains elusive. Results obtained from this study provides a way to further explore
the factors responsible for intact regional glutamate levels in female AD mice. |
| 4039.
 | 16 | Longitudinal changes of in vivo Quantitative Susceptibility Mapping (QSM) in the 3xTg-AD mouse model of Alzheimer's disease Qiong Ye1, Ziyi Wang2, Hui Li2, Bowen Shi2, and Garth J Thompson2
1High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China, 2iHuman Institute, ShanghaiTech University, Shanghai, China Keywords: Quantitative Imaging, Alzheimer's Disease, Quantitative susceptibility mapping Motivation: To investigate the longitudinal change of in vivo QSM of 3xTg-AD mice, age matched wile-type (WT) mice were used as a reference group. Goal(s): The regional variation of in vivo QSM in 3xTg-AD mice, and how they change with ageing. To investigate the sensitivity of in vivo QSM to the pathophysiological changes in 3xTg-AD mice. Approach: The 3xTg-AD and WT mice with 22 and 40 weeks old were scanned. A 3D multi-echo gradient echo sequence (mGRE) was acquired for the quantification of QSM. Results: Notable differences in QSM values were observed between various brain regions across ages and genotypes. Impact: The in vivo QSM of the mouse brain can be
obtained within approximately 21 minutes of scanning time. Significant
variations were observed between different age groups and genotypes in various
brain regions closely associated with the pathophysiology of Alzheimer's disease. |