Kirsten M Lynch¹, Giuseppe Barisano¹, Arthur W Toga¹, and Farshid Sepehrband^1
1Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, United States

The perivascular space (PVS) is a major component of the glymphatic system and it promotes functional brain clearance. PVS enlargement has been observed in neurological disorders and is considered a biomarker for vascular pathology, however its role in normative development is not well understood. Using a novel technique to segment PVS, we sought to quantify age-related changes in PVS across the lifespan in a large cross-sectional cohort of cognitively normal individuals. We found age was significantly and positively associated with PVS throughout the brain and these results provide a first step towards understanding the typical evolution of brain clearance mechanisms. 

Yolanda Ohene¹, Ian F. Harrison¹, David L. Thomas^2,3,4, Mark F. Lythgoe ¹, and Jack A. Wells ^1
1Centre for Advanced Biomedical Imaging, UCL, London, United Kingdom, ²Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, UCL, London, United Kingdom, ³Dementia Research Centre, UCL Queen Square Institute of Neurology, UCL, London, United Kingdom, ⁴Wellcome Centre for Humans Neuroimaging, UCL Queen Square Institute of Neurology, UCL, London, United Kingdom

Multi-TE ASL technique detects a significant increase (32%) in blood-brain interface (BBI) permeability in the ageing brain. The change in BBI water permeability is associated with a marked increase (1.9 ± 0.4 fold) in expression of PDGFRβ, an index of pericyte coverage, and changes to aquaporin water channels and their anchoring proteins in the ageing brain. This technique is a promising non-invasive tool to measure age-related changes to the BBI, that may play a mechanistic role in the pathogenesis of neurodegenerative conditions.

Joseph Alisch¹, Nikkita Khattar¹, Richard Wonjoong Kim¹, Abinand C. Rejimon¹, Luis E. Cortina¹, Wenshu Qian¹, Mustapha Bouhrara¹, and Richard G. Spencer^1
1NIA, NIH, Baltimore, MD, United States

Cerebral blood flow (CBF) has been shown to decline with age and differs between men and women. However, limited work has been conducted on cognitively unimpaired subjects. Furthermore, most investigations focus on gray matter (GM), with few results reported for white matter (WM), in which CBF is lower and represents a particularly challenging measurement. We investigate associations of age and sex with CBF in GM and WM regions in a cohort of cognitively unimpaired subjects across a wide age range.  We find significant correlations between CBF and age, as well as sexual dimorphism of CBF, in critical brain structures.
 

Yongxian Qian¹, Karthik Lakshmanan¹, Yulin Ge¹, Yvonne W. Lui¹, Thomas Wisniewski², and Fernando E. Boada^1
1Radiology, New York University, New York, NY, United States, ²Neurology, New York University, New York, NY, United States

This study presents preliminary data to demonstrate the potential of dynamic sodium MRI for mapping cerebrospinal fluid (CSF) bulk flow in extracellular space of tissues in whole brain.

Abigail Cember^1,2, Puneet Bagga¹, Hari Hariharan¹, and Ravinder Reddy^1
1Center for Magnetic Resonance and Optical Imaging, University of Pennsylvania, Philadelphia, PA, United States, ²Graduate Group in Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, United States

In investigating the problem of CEST correction methods for low saturation B₁, we observed differences in the behavior of the CEST asymmetry signal as a function of age. We believe this incidental observation to be a manifestation of the low saturation power induced NOE reported in other literature. In this case, we hypothesize that the physiological phenomenon underlying the pattern we observe is a decrease in myelin or other lipids in the aging brain. Our T₁ maps corroborate literature collected at lower field strength that T₁ values increase with age; however, this appears to be an independent, if related, phenomenon. 

Manoj K. Sammi¹, Katherine Powers¹, Chloe Robinson¹, Selda Yildiz^1,2, Miranda Lim^2,3,4,5,6, Jeffrey J Iliff^7,8,9,10,11, and William D Rooney^1,2,5,9
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Department of Neurology, Oregon Health & Science University, Portland, OR, United States, ³VA Portland Health Care System, Portland, OR, United States, ⁴Department of Medicine, Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, United States, ⁵Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States, ⁶Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, United States, ⁷Department of Neurology, University of Washington, Seattle, WA, United States, ⁸Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States, ⁹Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States, ¹⁰VISN 20 Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, WA, United States, ¹¹Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States

Lactate dynamics during sleep-awake cycle in human brain are studied non-invasively using single voxel diffusion weighted magnetic resonance spectroscopy (MRS) technique with simultaneous polysomnography (PSG) recordings to characterize sleep stages. Awake lactate apparent diffusion coefficients (ADC) values are large compared to other brain metabolites and may support active transport - Astrocyte-Neuron Lactate Shuttle (ANLS) mechanism. Lactate ADC are reduced in deep sleep stage in young subjects but are unchanged in older subjects.  These results may reflect different interstitial fluid exchange activity or changed metabolic state with aging and require further research.

Chaitali Anand¹, Dalal Khatib¹, Cheryl Dahle², Naftali Raz², and Jeffrey Stanley^1
1Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI, United States, ²Psychology, Wayne State University, Institute of Gerontology, Detroit, MI, United States

Memory declines early in normal aging, worsening in dementia. Glutamatergic neurons, abundant in the hippocampus, play a pivotal role in synaptic plasticity underlying formation of associations. We have previously demonstrated with ¹H fMRS, significant modulation of hippocampal glutamate during encoding of object-location associations. We observed that the timing of modulation differentiated proficiency in acquiring the associations. Because age-related hippocampal atrophy may be accompanied by glutamatergic dysfunction, age-differences in task-related levels of hippocampal glutamate may provide a marker of age-related memory deficits. Here, we identified age-differences in hippocampal glutamate modulation during associative memory encoding, which may underlie age-related associative memory deficits.

Peyton L Delgorio¹, Lucy V Hiscox¹, Ryan T Pohlig¹, Faria Sanjana¹, Ana M Daugherty², Hillary Schwarb³, Christopher R Martens¹, Matthew DJ McGarry⁴, and Curtis L Johnson^1
1University of Delaware, Newark, DE, United States, ²Wayne State University, Detroit, MI, United States, ³University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Dartmouth College, Hanover, NH, United States

The goal of this study is to generate the first high-resolution magnetic resonance elastography (MRE) protocol specifically for characterizing viscoelasticity of the hippocampal subfields (HCsf) and analyzing the effects of age on HCsf properties. We demonstrated that the protocol can sensitively and reliably differentiate between HCsf regions. We find that each HCsf decreases in stiffness and increases in damping ratio with age, and that HCsf exhibit differential relationships with age. This protocol shows promise for investigating the HCsf in health and disease.

Koji Kamagata¹, Christina Andica¹, Kazunori Shimada², Hideyoshi Kaga³, Yuki Someya^3,4, Yuya Saito^1,5, Toshiaki Akashi¹, Akihiko Wada¹, Yoshifumi Tamura^3,4, Ryuzo Kawamori^3,4, Hirotaka Watada³, Hiroyuki Daida², and Shigeki Aoki^1
1Department of Radiology, Juntendo University, Tokyo, Japan, ²Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan, ³Department of Metabolism & Endocrinology, Juntendo University, Tokyo, Japan, ⁴Sportology Center, Juntendo University, Tokyo, Japan, ⁵Department of Radiological Sciences, Tokyo Metropolitan University, Tokyo, Japan

Arterial stiffness has been shown to be associated with structural and functional abnormalities in the brain; however, white matter pathology related to arterial stiffness is poorly understood. In this study, we used white matter (WM) sensitive techniques (diffusion tensor imaging, neurite orientation dispersion and density imaging, free-water imaging, and magnetization transfer-saturation imaging) to better understand the impact of arterial stiffness on the WM microstructure in healthy elderly individuals. Our results suggest that arterial stiffness largely affects the content of cerebral myelin, as reflected by the myelin volume fraction.

Qiyuan Tian^1,2, Qiuyun Fan^1,2, Kimberly A. Stephens¹, Chanon Ngamsombat¹, Maya Polackal¹, Brian E. Edlow¹, Jennifer A. McNab³, David Salat¹, and Susie Y. Huang^1,2
1Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Department of Radiology, Harvard Medical School, Boston, MA, United States, ³Department of Radiology, Stanford University, Stanford, CA, United States

Return-to-origin probability (RTOP) measures the overall restriction of the microstructural environment and has been used to map microstructural changes related to age and pathology. However, measurement of RTOP requires either specialized acquisition (Cartesian q-space sampling) or processing (q-space gridding or modelling). We show that RTOP from multi-shell data is a weighted summation of the spherical mean signal of each individual shell. We apply our method to a multi-shell dataset of 40 subjects with b-values up to 17,800 s/mm2 and a dataset of 160 subjects from Lifespan Human Connectome Project in Aging and demonstrate its utility in mapping age-related microstructural change.

Inge Verheggen¹, Joost de Jong², Martin van Boxtel¹, Frans Verhey¹, Jacobus Jansen^2,3, and Walter Backes^2
1Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands, ²Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ³Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

Blood-brain barrier (BBB) disruption is assumed to increase with age, but this has not been demonstrated assessing gadolinium leakage using dynamic contrast-enhanced MRI.

We determined BBB leakage rate in healthy middle-aged to elderly individuals (47 - 91 years) combining DCE MRI with pharmacokinetic modeling. Results demonstrated BBB leakage in white and gray matter increased with age. However, this effect was not independent of white matter lesions or cortical thinning, so other physiological changes may influence the age and leakage association.Our study demonstrates that BBB disruption manifests in normal aging, before the emergence of neuropathology.

Elior Drori¹, Shir Filo¹, and Aviv Mezer^1
1The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

To date there are no in vivo tools for quantifying spatial changes in the microstructure of subcortical gray-matter nuclei. We have developed a quantitative MRI tool, with which we measured variations along the human dorsal striatum, using quantitative T1. We found monotonic gradients along the main axes, consistent with known biological gradients of the striatum. In addition, we found effects of laterality, as well as aging effects. Our method can prove useful for detection and quantification of microstructural irregularities in the striatum in patients suffering from basal ganglia disorders, such as Parkinson’s disease and ADHD.

Abdur Raquib Ridwan¹, Mohammad Rakeen Niaz¹, Yingjuan Wu¹, 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

One of the major challenges in constructing a longitudinal structural template of the older adult brain is to ensure spatio-temporal consistency. In this work, a new method was introduced to construct a spatio-temporally consistent longitudinal structural template of the older adult brain based on high quality cross-sectional older adult data from a large cohort. The new template was compared to templates generated with previously published methods in terms of spatio-temporal consistency, image quality, and representativeness of age-related brain changes, and was shown to have superior performance.  

Nahla M H Elsaid^1,2, Pierrick Coupé^3,4, Andrew J Saykin^1,2, and Yu-Chien Wu^1,2
1Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, United States, ²Indiana Alzheimer Disease Center, Indiana University, Indianapolis, IN, United States, ³LaBRI, UMR 5800, University of Bordeaux, Talence, France, ⁴LaBRI, UMR 5800, PICTURA, F-33400, CNRS, Talence, France

The aging process is known to cause morphological and structural alterations in the human brain.  Using a sub-millimeter super-resolution hybrid diffusion imaging (HYDI), we studied the effects of aging on the structural connectivity between the hippocampal subfields as well as between the hippocampus and the cerebral cortex.

Yan Li¹, Sean K. Sethi^2,3, Chengyan Wang⁴, Weibo Chen⁵, Naying He¹, Ewart Mark Haacke³, and Fuhua Yan^1
1Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ²The MRI Institute for Biomedical Research, Magnetic Resonance Innovations, Inc., Detroit, MI, United States, ³Department of Radiology, Wayne State University, Detroit, MI, United States, ⁴Human Phenome Institute, Fudan University, Shanghai, China, ⁵Philips Healthcare, Shanghai, China

To investigate the correlation of iron content in deep gray matter nuclei as a function of age by reconstructed quantitative susceptibility mapping (QSM) using both whole-structural and regional perspectives from three different MRI sites and three different scanners to show that QSM is a robust technology across manufacturers and resolution.