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Courtney J Comrie¹, Laurel A Dieckhaus¹, Tom G Beach², Geidy E Serrano², and Elizabeth B Hutchinson^1
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States, ²Brain and Body Donation Program, Banner Sun Health Research Institute, Sun City, AZ, United States

Keywords: Alzheimer's Disease, Alzheimer's Disease

Alzheimer’s is an irreversible degenerative brain disease. Clinical MRI may visualize severe brain atrophy but fails to recognize earlier biomarkers associated with subtle microstructural changes. Microstructural MRI techniques such as DTI, MAP-MRI, and MSDKI may sensitively detect and distinguish tissue degeneration, tauopathies, and beta amyloid plaques in the hippocampus and entorhinal cortex. The capability of these techniques was investigated in post-mortem human temporal lobe specimens at high resolution and high image quality. Prominent findings seen were differences between DTI and MAP-MRI anisotropy metrics, and striking differences between the hippocampus and entorhinal cortex for restriction due to plaques.

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Yingjuan Wu¹, Abdur Raquib Ridwan², Mohammad Rakeen Niaz¹, David A. Bennett², and Konstantinos Arfanakis^1,2
1Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, United States

Keywords: Alzheimer's Disease, Aging, Atlas

A high quality FOD template of the older adult brain can enhance the sensitivity and accuracy of white matter investigations in older adults. The present work compared several FOD template construction methods for the purpose of developing a high-resolution FOD template of the older adult brain in the space of the MIITRA atlas. The preferred method employed multichannel registration based on T1w, FA and FOD information, followed by additional FOD single modality registration. The resulting FOD template exhibited high image quality, was constructed based on precisely matched FOD data, and exhibited high spatial matching to other existing MIITRA templates.

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Kurt Schilling¹, Francois Rheault², Dmitri Shastin³, Leon Y Cai⁴, Andrea T Shafer⁵, Susan M Resnick⁵, Bennett A Landman⁴, and Maxime Chamberland^6
1VUMC, Nashville, TN, United States, ²Sherbrooke University, Sherbrooke, QC, Canada, ³Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, United Kingdom, ⁴Vanderbilt University, Nashville, TN, United States, ⁵National Institute on Aging, Baltimore, MD, United States, ⁶Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands

Keywords: Alzheimer's Disease, Alzheimer's Disease

Medical imaging is a promising tool in detecting altered brain tissue states related to cognitive impairment and dementia, however, clinical heterogeneity challenges interpretation of these changes. Recent work in normative modeling has paved the way for not only group-based comparisons of control/cohorts, but detection of deviations in individual subjects. Here, we apply this framework to detect anomalies in individuals with cognitive impairment by assessing the classification power of microstructural and macrostructural features of different tissue types, and also attributing anomalies to specific features of brain tissue. 

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Jennapher Lingo VanGilder¹, Leslie C. Baxter², Andrew Hooyman¹, Leland S. Hu³, Yuxiang Zhou³, Richard J. Caselli⁴, Kurt G. Schilling⁵, and Scott C. Beeman^1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States, ²Psychiatry and Psychology, Mayo Clinic, Scottsdale, AZ, United States, ³Radiology, Mayo Clinic, Scottsdale, AZ, United States, ⁴Neurology, Mayo Clinic, Scottsdale, AZ, United States, ⁵Radiology, Vanderbilt University, Nashville, TN, United States

Keywords: Alzheimer's Disease, Alzheimer's Disease, ApoE4; genetic-risk

We have recently shown that the functional connectivity of the left hippocampus is significantly related to memory trajectory in cognitively intact ApoE4 carriers, independent of hippocampal volume. The purpose of this preliminary study was to determine if dendritic orientation dispersion of the left hippocampus explains variance in delayed verbal memory in this cohort. Results indicated that dendritic complexity of the left hippocampus was related to delayed memory in ApoE4 carriers. These findings suggest that ApoE4 carriers may experience subtle microstructural declines in the left hippocampus at the cognitively-intact stage.

Meng Li¹, Shanwen Liu², Yuqi Zhi¹, Rong Liu¹, Zhen Jiang¹, Xiaoyun Liang^3,4, Hua Hu², Yunzhu Wu⁵, Yang Song⁵, and Jiangtao Zhu^1
1Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China, ²Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China, ³Institute of Artificial Intelligence and Clinical Innovation, Neusoft Medical Systems Co., Ltd., Shanghai, China, ⁴Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia, ⁵MR Scientific Marketing, SIEMENS Healthineers Ltd., Shanghai, China

Keywords: Alzheimer's Disease, Alzheimer's Disease

We collected diffusion-weighted images of all subjects and divided them into four groups: HC, MCI, mild AD and moderate AD. The differences of FD, FC and FDC were analyzed by FBA method. The results showed that the three metrics in AD group were significantly lower than those in HC Group, but there was no significant difference in MCI Group. This study indicates that there is a microstructural or macrostructural degeneration in the white matter of AD patients.

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Wenji Xu¹, Xiaochun Wang², Hui Zhang², and Yan Tan*^2
1College of Medical Imaging, Shanxi Medical University, Taiyuan, China, ²Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan, China

Keywords: Alzheimer's Disease, Alzheimer's Disease, Alzheimer’s disease; aluminum exposure; diffusion kurtosis imaging

In this work, we focused on the Al-exposed workers and  confirm the findings that DKI can discriminate MCI from NC, furthermore we assess the severity of cognitive impairment in Al-exposed workers, and find the MK, Kr, MD and FA values are correlated with MoCA scores，which may provide quantitative imaging biomarkers for Al-exposed MCI workers.

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Samantha N Schatz¹, Courtney J Comrie¹, Laurel A Dieckhaus¹, and Elizabeth B Hutchinson^1
1University of Arizona, Tucson, AZ, United States

Keywords: Alzheimer's Disease, Diffusion Tensor Imaging, Repository Data, Cognitive Impairment, Tensor Based Morphometry, Hippocampus

Alzheimer's disease is generally accompanied by brain atrophy, which can be evident on MRI based evaluation at late stages, but there is a need for earlier stage MRI markers that may predict progressive cognitive impairment. Using the NACC Uniform Data Set, a robust pipeline was developed for registering DTI maps to a Human Connectome Project template space and an analysis framework for ROI based, voxel-wise, and morphometric analysis was applied. Prominent results include increased trace in the hippocampus and an increase in ventricle volume in the group with severe cognitive impairment.

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Elizabeth Hutchinson¹, Jean-Pierre Galons², Courtney Comrie¹, Seraphina Solders³, Geidy Serrano⁴, Thomas Beach⁴, Vitaly Galinsky³, and Lawrence Frank^3
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States, ²Medical Imaging, University of Arizona, Tucson, AZ, United States, ³Center for Scientific Computing in Imaging, University of California, San Diego, CA, United States, ⁴Banner Sun Health, Sun City, AZ, United States

Keywords: Alzheimer's Disease, Diffusion/other diffusion imaging techniques, double diffusion encoding

Double diffusion encoding (DDE) MRI provides unique sensitization to microscale anisotropy although scalar representation of DDE data is challenging. The diffusion tensor subspace imaging (DiTSI) framework generates metrics from DDE images. In this study, post-mortem human brain tissue specimens were imaged and comparative analysis found that DiTSI but not DTI was able to provide distinct contrast in gray matter regions and at the gray/white interface. Additionally, small cranial nerve fibers of the brain stem were detectable using DiTSI, but not DTI or NODDI approaches and also showed remarkable abnormalities in Alzheimer’s disease tissue that were absent for DTI.

Aniket Aman¹, Neha Yadav¹, Arkaprava Majumdar¹, and Vivek Tiwari^1
1Department of Biological Sciences, Indian Institute of Science Education and Research, Berhampur, Berhampur, India

Keywords: Dementia, Aging, White Matter Hyperintensity, APOE E4, Cognition, Hypertension

Transformation of brain heath with aging comprehend a series of brain structure, vascular and functional changes over time. The key to understanding the brain health in normal and pathological aging is to identify the series of early, intermediate and late events that encodes for brain health. Here, we have investigated the temporal and spatial orders of brain volumetry, small vessel pathology (white matter hyperintensity) and its kinetics with normal aging and aging with cardiovascular risks and gene defects such as APOE ε4, across subjects classified as cognitively Normal (CN), Mild Cognitive Impairment (MCI) and Dementia (DM).

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Jasmin A. Keller¹, Sigurdur Sigurdsson ², Mark A. van Buchem¹, Lenore J. Launer³, Matthias J.P. van Osch¹, Vilmundur Gudnason^2,4, and Jeroen H.J.M. de Bresser^1
1Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Icelandic Heart Association, Kopavogur, Iceland, ³Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, MD, United States, ⁴Faculty of Medicine, University of Iceland, Reykjavik, Iceland

Keywords: Dementia, Aging, Cerebral small vessel disease

White matter hyperintensity (WMH) shape was recently introduced as a novel small vessel disease (SVD) marker that may provide a more detailed characterization of WMH than volume alone. We aimed to investigate the association between baseline WMH shape and cerebrovascular disease progression over 5 years. A more irregular shape of periventricular/confluent and deep WMH at baseline is associated with increased progression of WMH volume. Moreover, a more irregular shape of periventricular/confluent WMH was associated with occurrence of new microbleeds and new subcortical infarcts at follow-up. Our findings indicate that a more irregular WMH shape is associated with SVD progression.

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Michal R Tomaszewski¹, Alexander L Sukstansky², Hyking Haley¹, Xiangjun Meng¹, Corey O Miller¹, and Dmitriy A Yablonskiy^2
1Translational Imaging, Merck & Co, West Point, PA, United States, ²Mallinckrodt Institute of Radiology, Washington University, St Louis, MO, United States

Keywords: Alzheimer's Disease, Animals

There is an unmet need for non-invasive technique for measurement of neurodegeneration in Alzheimer’s Disease (AD). Quantitative Gradient-Recalled-Echo (qGRE) MRI showed promise to address this in patients through quantification of tissue specific R2* relaxation showing neurodegeneration before atrophy. Here qGRE is optimized and applied for the first time to measure progression of this preatrophic neurodegeneration in Tg4510 mouse model of AD. Histological neuronal density quantification and test-retest measurements validated R2* measurements. We showed significant decrease in normalized median hippocampus R2* between 3, 5 and 6 month-old Tg4510 mice. The method can be applied in AD drug discovery and model development.

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Anjan Bhattarai ^1,2, Pauline Maillard¹, Charles DeCarli¹, and Audrey Fan^1,2
1Department of Neurology, University of California Davis, Davis, CA, United States, ²Department of Biomedical Engineering, University of California Davis, Davis, CA, United States

Keywords: Alzheimer's Disease, Diffusion/other diffusion imaging techniques, Fixel based analysis

We investigated fibre tract-specific changes in the whole-brain white matter in individuals with   Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) using Fixel Based Analysis (FBA). The results show significant reduction in microstructural fibre bundles in AD, in regions including splenium of the corpus callosum, fornix, and the uncinate fasciculus. FBA-derived measures, including fibre density (FD), and combination of fibre density and cross-section (FDC) demonstrated sensitivity in detecting microstructural white matter alterations in AD. These findings highlight the utility of FBA as a potential biological marker for providing valuable insights into pathophysiologic changes in AD.

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Rasheed Abid¹, Abdur Raquib Ridwan², Yingjuan Wu¹, Mohammad Rakeen Niaz¹, Shengwei Zhang², Arnold M. Evia², David A. Bennett², and Konstantinos Arfanakis^1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, United States

Keywords: Alzheimer's Disease, Aging, Brain, Susceptibility, Atlas

Quantitative susceptibility mapping (QSM) is considered a promising tool for the detection and monitoring of disease processes that alter magnetic susceptibility in the brain of older adults. Voxel-wise and atlas-based QSM analyses require accurate spatial normalization of QSM data, which requires a high quality QSM template representative of the population. However, a QSM template of the older adult brain is not yet available. This study aimed to construct a high quality, high resolution QSM template of the older adult brain in the space of the MITRA atlas based on data from a large, diverse, community cohort of non-demented older adults.

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Jonghyun Bae^1,2,3, Ayesha Das³, Isabel Reyes⁴, Sawwal Qayyum⁵, Jin Zhang⁵, Arjun Masurkar⁴, and Sungheon Gene Kim^5
1Vilcek Institute of Graduate Biomedical Science, NYU School of Medicine, New York, NY, United States, ²Center for Advanced Imaging Innovation and Research, Radiology, NYU School of Medicine, New York, NY, United States, ³Radiology, Weill Cornell Medical College, New York, NY, United States, ⁴Neurology, NYU Langone Health, New York, NY, United States, ⁵Weill Cornell Medical College, New York, NY, United States

Keywords: Alzheimer's Disease, Aging

Recent studies have suggested that the increase in blood-brain barrier (BBB) permeability is associated with both aging and the progression of the Alzheimer’s disease (AD). However, the association of the amyloid pathology with the increased BBB leakage at different disease progression is still poorly understood. In this study, we performed a cross-sectional study to investigate the BBB permeability changes in AD transgenic mice with aging. We also propose the network-aided analysis allows the scan time reduction without compromising the accuracy of the detection of the subtle permeability

Ying Hu¹, Yawen Sun¹, Yiming Zhang¹, and Yan Zhou^1
1Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Keywords: Dementia, Aging

NVC is thought to reflect the interrelationship between nutrient demand and supply, whereby neuronal activity influences local changes in blood flow. Injuries to the NVU could be the crucial point to CSVD, but the mechanisms remain obscure. This is the first study investigating CSVD from the perspective of the NVC at the whole brain, modular and regional levels.

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Xiang Fan^1,2, Yuan Cai², Wanting Liu², Lin Shi², and Vincent CT Mok^2
1Peking University Shenzhen Hospital, Shenzhen, China, ²The Chinese University of Hong Kong, Hong Kong, SAR, China

Keywords: Alzheimer's Disease, Alzheimer's Disease

Alzheimer's disease (AD) resemblance atrophy index (AD-RAI) is a novel MRI-based machine-learning derived imaging biomarker for AD that is valid in detection of early AD. We selected 318 CU and MCI subjects in ADNI with four-year follow-up with 1471 serial MRI scans to assess longitudinal changes of the MRI biomarkers (i.e., AD-RAI, HV, HF, BPV, BPF) in correlation with the change in time and conversion status. We used generalized linear mixed-effects models to compute and show the predictive value. AD-RAI over time showed the highest classification accuracy for predicting converters when compared with other imaging biomarkers.

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Surendra Maharjan¹, Megan Renate Jewett¹, Abigail Wallace¹, and Nian Wang^1,2
1Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ²Stark Neurosciences Research Institute, Indianapolis, IN, United States

Keywords: Alzheimer's Disease, Alzheimer's Disease, mice

Alzheimer’s disease is a common neurodegenerative dementia. Although disease has no cure, early intervention can help to maintain normal mental function and slow down the progression of the disease. A comprehensive study incorporating diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), brain connectivity and fixel-based analysis (FBA) is still lacking. Hence, we aim to apply these methods in a novel SAA mouse model of Alzheimer’s disease. We found there was significant difference in cortex and hippocampus in between control B6 and SAA groups.

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Shu Matsushita¹, Hiroyuki Tatekawa¹, and Yukio Miki^1
1Department of Diagnostic and Interventional Radiology, Osaka Metropolitan University, Osaka, Japan

Keywords: Alzheimer's Disease, Alzheimer's Disease

Revealing the association of amyloid PET and metabolic MRI measurements would be useful for future studies or clinical situations that evaluate Alzheimer's disease (AD). We investigated the relationship between imaging measurements and clinical information in 29 AD patients and age- and sex-matched normal controls (NCs) using OASIS-3 dataset. A significant positive correlation was found between brain temperature and index of diffusivity along the perivascular space (ALPS index) among all subjects and NCs, while a significant negative correlation was found between age and ALPS index among all subjects, AD patients, and NCs.

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Katherine Anne Koenig¹, Sally Durgerian¹, Mark J Lowe¹, Frank DiFilippo¹, Lynn Bekris¹, James Leverenz¹, and Stephen Rao^1
1The Cleveland Clinic, Cleveland, OH, United States

Keywords: Alzheimer's Disease, Alzheimer's Disease, APOE

The apolipoprotein E (APOE) ε4 genotype is a genetic risk factor for late onset Alzheimer’s Disease (AD). Consistent differences in network connectivity have been described in ε4 carriers (e4+). Here, we compare resting state connectivity in the default mode network between elderly, cognitively intact e4+ and non-carriers (e4-) and assess the relationship of connectivity to AD-related biomarkers. Regional changes in the e4+ group primarily consisted of weakened connectivity. Connectivity strength in the middle temporal gyrus was negatively related to amyloid PET centiloid score and p-tau in the e4+ group. 

Xin Chen¹, Tao Gong¹, and Weibo Chen^2
1Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China, ²Philips Healthcare, Shanghai, China

Keywords: Alzheimer's Disease, Alzheimer's Disease

Amnestic mild cognitive impairment (aMCI) is a precursor to Alzheimer's disease (AD). The neurometabolic changes especially the neurotransmitters in the hippocampus contributed the course of AD. In-vivo magnetic resonance spectroscopy (MRS) can be used to measure brain metabolites noninvasively. In this study, we aim to explore the changes of hippocampal metabolic changes in aMCI patients using PRESS and MEGA-PRESS. aMCI patients exhibited decreased hippocampal Glx levels from MEGA-PRESS, having low concordance with PRESS.