Luis E. Cortina¹, Richard G. Spencer¹, and Mustapha Bouhrara^1
1NIA, Baltimore, MD, United States

Brainstem tissue microstructural properties change across the adult lifespan. However, investigations elucidating the biological processes that govern brainstem maturation and degeneration are lacking. Here, we implement a multi-parameter approach to characterize the sex- and age-differences in a large cognitively unimpaired adult cohort. Our findings demonstrate quadratic associations between MR metrics and age as well as sexual dimorphism in certain MR metrics. Finally, our results indicate that myelination follows a temporally symmetric time course across the adult lifespan, while axons appear to degenerate significantly more rapidly than they mature.

Maurizio Bergamino¹, Elizabeth G Keeling^1,2, Ryan R Walsh³, and Ashley M Stokes^1
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²School of Life Sciences, Arizona State University, Tempe, AZ, United States, ³Muhammad Ali Parkinson Center at Barrow Neurological Institute, Phoenix, AZ, United States

The objective of this study was to investigate differences in white matter (WM) integrity and grey matter (GM) volumes between males and females in healthy aging and Alzheimer’s Disease using free-water diffusion tensor imaging (FW-DTI) and voxel-based morphometry (VBM) analyses, respectively.

Mohammad Rakeen Niaz¹, Yingjuan Wu¹, Abdur Raquib Ridwan¹, Xiaoxiao Qi¹, 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

The Multichannel Illinois Institute of Technology & Rush university Aging (MIITRA) atlas contains high resolution (0.5mm) T1-weighted (T1w) and diffusion tensor imaging (DTI) templates, constructed using high quality MRI data on a large (N=400), diverse, community cohort of non-demented older adults. The purpose of this work was twofold: a) to construct high resolution gray matter labels for the MIITRA atlas based on manually edited gray matter labels of the older adults included in the atlas, and b) to evaluate the performance of the new labels in labeling the gray matter of a separate group of older adults.

fei gao¹, fuxin ren¹, weibo chen², and muwei li^3
1Shandong Medical Imaging Research Institute, Shandong University, jinan, China, ²Philips Healthcare, shanghai, China, ³Vanderbilt University Institute of Imaging Science, Nashville, TN, United States

Previous studies have linked Presbycusis (PC) to cognitive impairment and incident Alzheimer’s disease. However, the neural mechanisms of cognitive impairment in patients with PC remain unclear. Although resting-state functional MRI studies have explored low-frequency oscillation (LFO) connectivity or amplitude of PC-related neural activity, it remains unclear whether the abnormalities occur within all frequency bands or within specific frequency bands. Therefore, we applied ALFF to examine changes in LFO amplitudes in PC patients at different frequency bands (slow-4 and slow-5). Then, we used brain regions showing altered ALFF as seeds to explore FC between these regions and all other brain voxels.

Geon-Ho Jahng^1,2, Ji Yoon Lee³, Seung-Hyun Lim¹, Hak Young Rhee⁴, Soonchan Park^1,2, Jongho Lee⁵, and Chang-Woo Ryu^1,2
1Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of, ²Medicine, Kyung Hee University, Seoul, Korea, Republic of, ³Biomedical Engineering, Kyung Hee University, Yongin-si, Korea, Republic of, ⁴Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of, ⁵Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of

The objective of this study was to investigate myelin loss in participants with AD, MCI, and cognitively normal (CN) elderly using the whole brain MWF map. The ViSTa-GRASE sequence provides the good MWF map in a reasonable scan time to evaluate myelin loss in AD patients. MWF was significantly reduced in AD compared with CN, indicating the presence of widespread demyelination in AD. In addition, MWF was significantly correlated with memory decline, indicating that MWF could serve as a potential imaging biomarker for AD for evaluating demyelination and predicting treatment outcomes.

Yangyingqiu Liu¹, Yanwei Miao¹, Ailian Liu¹, Lizhi Xie², and Bing Wu^2
1Department of Radiology, First Affiliated Hospital of Dalian Medical University, Dalian, China, ²GE healthcare, Beijing, China

Iron deposition of the gray matter nucleus is quantitatively assessed by magnetic sensitivity value (MSV)using quantitative susceptibility mapping (QSM), and its’correlation to cognitive scores is also analyzed in patients with Alzheimer's disease (AD).The results show that increased MSV value of gray matter nucleus in AD patients may affect cognitive scores.  

Geon-Ho Jahng^1,2, Chang Hyun Yoo³, Seokha Jin⁴, DongKyu Lee⁴, and HyungJoon Cho^4
1Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of, ²Medicine, Kyung Hee University, Seoul, Korea, Republic of, ³Physics, Kyung Hee University, Seoul, Korea, Republic of, ⁴Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Korea, Republic of

We simulated the changes in microvascular (MV) MRI signals with and without existing amyloid-beta plaques or microbleeds in an imaging voxel. The Monte Carlo simulations with the finite perturber method were used to calculate MV indices of mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), blood volume fraction (BVf), and microvessel-weighted imaging (MvWI). The simulation was performed with three different voxel environmental conditions: only the MV structures, MV structures with amyloid-beta plaques, and MV structures with microbleeds.

Geon-Ho Jahng^1,2, Ji Yoon Lee³, Hak Young Rhee⁴, Wonchae Choe⁵, and Chang-Woo Ryu^1,2
1Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of, ²Medicine, Kyung Hee University, Seoul, Korea, Republic of, ³Biomedical Engineering, Kyung Hee University, Yongin-si, Korea, Republic of, ⁴Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of, ⁵Biochemistry and Molecular Biology, Kyung Hee University, Seoul, Korea, Republic of

We evaluated the relationship between imaging biomarker by GMV changes and blood biomarkers by plasma levels of HO-1, PPIA, and IRE1 in the groups of cognitively normal (CN), amnestic mild cognitive impairment (MCI), and AD participants. Our study demonstrates that subjects with AD have lower circulating levels of HO-1 than subjects with MCI and the plasma HO-1 levels were positively associated with the global GMV. Considering the potential roles of each enzyme in pathogenesis of AD, the plasma circulating levels of these enzymes possibly reflect the pathological changes of the brain in AD and would be candidates for blood-based biomarkers.

Xiuxiu Liu¹, Lei Du^1,2, Wenwen Gao¹, Bing Liu^1,2, Yue Chen¹, Yige Wang^1,2, Guolin Ma¹, and Weiyin Liu^3
1Department of Radiology, China-Japan Friendship Hospital, Beijing, China, ²Graduate School of Peking Union Medical College, Beijing, China, ³GE Healthcare, Beijing, China

Whether excessive iron deposition in basal ganglia of Alzheimer’s patients can affect the diffusion function of white matter is still unknown. There were 30 Alzheimer’s patients and 19 healthy controls in this study. We used diffusion tensor imaging and quantitative susceptibility mapping to discover the alterations of diffusion function and magnetic susceptibility of brain and associations between diffusion indexes, magnetic susceptibility, and cognitive function. This study revealed that diffusion indexes and magnetic susceptibility changed which were related to cognitive impairment. In addition, increasing magnetic susceptibility due to iron deposition may adversely affect the diffusion function of brain.
 

Erik Taylor^1
1Radiology, University of New Mexico, Albuquerque, NM, United States

Diseases with age as the primary risk factor increase in prevalence as life expectancy increases. Aging is implicated in cardiovascular (CV) disease and neurodegeneration. As the stiffness of the proximal aorta increases, damaging pulses of pressure have been postulated to propagate into the brain. The purpose of this study was to relate vascular and brain pathology through non-invasive measures in normal and hypertensive rodents. Brain pathology was detected by multiple MRI contrast mechanisms, while specific vascular parameters were derived from ultrasound in the aorta. Non-invasive measures relating brain and vascular aging could aid in the future development of therapeutic strategies.

Xiaole Zhong¹ and J. Jean Chen^1,2
1Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada, ²Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Frequency and amplitude features for EEG and resting-state functional magnetic resonance imaging (rs-fMRI) data are individually used in human brain aging research. However, the association between the age effects on these two modalities is still unknown. In this study, we examined age effects on EEG and rs-fMRI from both frequency and amplitude perspectives. We found that while both EEG and fMRI are affected by age, there is no association between these respective age effects.  

Lucy V Hiscox¹, Emma M Tinney¹, Peyton L Delgorio¹, Matthew DJ McGarry², Alyssa Lanzi³, James M Ellison⁴, Matthew L Cohen³, Chris R Martens⁵, and Curtis L Johnson^1
1Department of Biomedical Engineering, University of Delaware, Newark, DE, United States, ²Dartmouth College, Hanover, NH, United States, ³Department of Communication Sciences & Disorders, University of Delaware, Newark, DE, United States, ⁴Swank Center for Memory Care and Geriatric Consultation, ChristianaCare, Wilmington, DE, United States, ⁵Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States

The health and integrity of the hippocampus is implicated in the development of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Neuroimaging techniques evaluate the characteristics of hippocampal health in vivo, including its size, diffusion properties, and blood flow. In this study, we show that the mechanical properties of the hippocampus, obtained through magnetic resonance elastography (MRE), are associated with an increased risk of MCI, when other techniques are not. Establishing risk based on practically relevant quantitative changes in neuroimaging variables can help identify participants likely to develop cognitive impairment and assist in establishing the effectiveness of treatment interventions.

Roman Fleysher¹, Mohammad Mansouri¹, and Michael L Lipton^1
1Radiology, Albert Einstein College of Medicine, Bronx, NY, United States

Despite best efforts, performance of automatic brain segmentation is inferior in older adults. We hypothesize that worsening of segmentation quality with age is related to brain atrophy and changes to image contrast. To disentangle the two possibilities, we simulated brain atrophy and confirmed worse segmentation performance. We then propose and demonstrate “brain rejuvenation” as a method to improve segmentation of the aged brain.

Maryam H. Alsameen¹, Wenshu Qian¹, Matthew Kiely¹, Curtis Triebswetter¹, Zhaoyuan Gong¹, and Mustapha Bouhrara^1
1National Institute on Aging, NIH, Baltimore, MD, United States

The NODDI approach has been shown to overestimate the CSF and neurite density (NDI) fractions in white matter. We propose a new modification to the NODDI algorithm to address these issues. Our approach requires minimal extension of the total acquisition time. While the neurite orientation dispersion (ODI) values were consistent between the two approaches, the modified NODDI approach provides lower, more physiologically plausible, NDI values as compared to those derived using the original NODDI approach. Further, NDI and ODI exhibit, overall, quadratic associations with age. These associations were more pronounced and significant from results derived using the modified NODDI approach.

 

Curtis G. Triebswetter¹, Nikkita Khattar¹, Matthew Kiely¹, Maryam H. Alsameen¹, Zhaoyuan Gong¹, Susan M. Resnick², and Mustapha Bouhrara^1
1Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, ²Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, United States

Little is known about the role of APOE isoforms in cerebral myelination. Although several quantitative MRI studies have demonstrated the influence of APOE on cerebral tissue integrity, its specific implication in brain myelination remains to be established. In this work, we investigated associations between APOE isoforms ε2 or ε4 and myelination, probed using specific and nonspecific measures of myelin content, in multiple brain regions in a cohort of cognitively unimpaired participants spanning a wide age range. We show significant correlations between APOE isoforms ε2 or ε4 and myelin content in several brain structures.

Caitlin F Fowler^1,2, Dan Madularu³, Gabriel A Devenyi^4,5, John Breitner^5,6, and Jamie Near^1,4,5
1Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada, ²Cerebral Imaging Centre, Douglas Hospital Research Centre, Verdun, QC, Canada, ³Center for Translational Neuroimaging, Northeastern University, Boston, MA, United States, ⁴Cerebral Imaging Centre, Douglas Hospital Research Institute, Verdun, QC, Canada, ⁵Psychiatry, McGill University, Montreal, QC, Canada, ⁶Division of Human Neurosciences, Douglas Hospital Research Centre, Verdun, QC, Canada

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no effective treatments or known biomarkers for definitive diagnosis, substantiating the need for early detection and intervention. This project employs Magnetic Resonance Spectroscopy to quantify neurochemical changes in the TgF344-AD rat model of AD in response to early versus late administration of a common non-steroidal anti-inflammatory drug, specifically addressing the critical question of treatment timing. Preliminary results suggest the TgF344-AD rat recapitulates most neurochemical features of human AD and that early treatment is more effective than late treatment at mitigating disease-related neurochemical changes.

M. Dylan Tisdall¹, Daniel Ohm², Rebecca Lobrovich², Sandhitsu R Das¹, Gabor Mizsei¹, Karthik Prabhakaran², Ranjit Ittyerah¹, Sydney Lim¹, Corey T McMillan², James Gee¹, John Q Trojanowski³, Edward B Lee³, David Wolk², John A Detre^1,2, Paul Yushkevich¹, Murray Grossman², and David Irwin^2
1Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ²Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ³Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

We describe novel, focal iron-rich pathology in frontotemporal lobar degeneration (FTLD), detected via combined ex vivo 7 T whole-hemisphere MRI and MRI-guided histopathology. While previous work has shown iron-positive plaques in AD, and focal iron-positive pathology in the motor cortex of ALS patients, we find novel focal pathologic features across a diverse range of FTLD patients, including both FTLD-tau and FTLD-TDP. These focal features occurred in regions often missed with standardized diagnostic sampling, demonstrating the sensitivity of an MRI-guided approach to histopathology. Additionally, these focal iron deposits are candidates for future in vivo detection, providing new sources of imaging contrast.

Abdur Raquib Ridwan¹, Yingjuan Wu¹, 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

Construction of an optimal T1-weighted (T1w) template for older adults often requires selection of a target anatomy for nonlinear-registrations, however a poorly chosen template may introduce bias due to large structural discrepancies between template and subjects used for template construction. Such a bias may introduce misregistration and cause loss of important anatomical details. In addition, large structural brain differences across older adults may introduce registration errors despite using state-of-the-art registration algorithms. The purpose of this work was to construct a minimum deformation T1w template of the older adult brain using a sparse, patch-based, detail-preserving template construction method that minimizes biases.

Jason F. Moody¹, Douglas C. Dean III^1,2,3, Steven R. Kecskemeti ³, Sterling C. Johnson^4,5, Barbara B. Bendlin⁴, and Andrew L. Alexander^1,3,6
1Department of Medical Physics, University of Wisconsin Madison, Madison, WI, United States, ²Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States, ³Waisman Center, University of Wisconsin Madison, Madison, WI, United States, ⁴Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin Madison, Madison, WI, United States, ⁵Geriatric Research Education and Clinical Center, Middleton Memorial VA Hospital, University of Wisconsin-Madison, Madison, WI, United States, ⁶Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, United States

We implement mean apparent propagator (MAP) MRI to investigate distinct white matter (WM) microstructural changes associated with aging and AD dementia. Age trajectories of MAP MRI parameters extracted from the cingulum, corpus callosum, and superior longitudinal fasciculus reveal evidence for structurally affected axons in aging populations.  Return to origin probability (RTOP) and non-Gaussianity (NG) age trajectories are significantly flatter in AD dementia subjects compared to healthy controls, indicating that these measures could serve as markers for WM deterioration characteristic of dementia. Our findings provide an early quantitative framework for identifying specific WM microstructural deficiencies associated with aging and dementia.

Tongtong Li¹, Yu Zhang¹, Xiuwei Fu², Xianchang Zhang³, Yuan Luo⁴, and Hongyan Ni^5
1First Central Clinical College, Tianjin Medical University, Tianjin, China, ²Tianjin Medical University General Hospital, Tianjin, China, ³MR Collaboration, Siemens Healthcare Ltd, Beijing, China, ⁴Department of Radiology, China-Japan Friendship Hospital, Beijing, China, ⁵Department of Radiology, Tianjin First Central Hospital, Tianjin, China

Previous studies that used diffusion kurtosis imaging to study Alzheimer's disease (AD) mostly analyzed data based on regions of interest method, which may be biased by subjectivity. This study used Tract-based Spatial Statistics (TBSS) method to analyze the DKI data and found that kurtosis fractional anisotropy (KFA) values outperformed other DKI-derived parameters in sensitive detection of microstructural white matter damage for early diagnosis of amnestic mild cognitive impairment (aMCI) and AD.