Abstract During aging, human white matter (WM) is subject to dynamic structural changes which have a deep impact on healthy and pathological evolution of the brain through the lifespan; characterizing this pattern is of key importance for understanding brain development, maturation and aging as well as for studying its pathological alterations. Diffusion Magnetic Resonance Imaging (MRI) can provide a quantitative assessment of the white-matter microstructural organization that characterizes these trajectories. Here, we use both conventional and advanced diffusion MRI in a cohort of 91 individuals (age range: 13-62) to study region- and sex-specific features of WM micro-structural integrity in healthy aging. We focus on the age at which microstructural imaging parameters invert their development trend as the timepoint which marks the onset of microstructural decline in WM. Importantly, our results indicate that age-related brain changes begin earlier in males than females and affect more frontal regions - in accordance with evolutionary theories and numerous evidences across non-MRI domains. Advanced diffusion MRI reveals age-related WM modifications patterns which cannot be detected using conventional DTI.
Age- and sex-related alterations in gene transcription have been demonstrated, however the underlying mechanisms are unresolved. Neuroepigenetic pathways regulate gene transcription in the brain. Here, we measure in vivo expression of the epigenetic enzymes, histone deacetylases (HDACs), across healthy human aging and between sexes using [11C]Martinostat positron emission tomography (PET) neuroimaging (n = 41). Relative HDAC expression increases with age in cerebral white matter, and correlates ...
: The human brain undergoes dramatic structural change over the life span. In a large imaging cohort of 801 individuals aged 7-84 years, we applied quantitative relaxometry and diffusion microstructure imaging in combination with diffusion tractography to investigate tissue property dynamics across the human life span. Significant nonlinear aging effects were consistently observed across tracts and tissue measures. The age at which white matter (WM) fascicles attain peak maturation varies substa...
Last. Susie Y. Huang(MIT: Massachusetts Institute of Technology)H-Index: 17
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Abstract Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to incr...
Abstract In multiple sclerosis (MS), it would be of clinical value to be able to track the progression of axonal pathology, especially before the manifestation of clinical disability. However, non-invasive evaluation of short-term longitudinal progression of white matter integrity is challenging. This study aims at assessing longitudinal changes in the restricted (i.e. intracellular) diffusion signal fraction (FR) in early-stage MS by using ultra-high gradient strength multi-shell diffusion magn...
#1Manu S. Goyal(WashU: Washington University in St. Louis)H-Index: 17
#2Tyler Blazey(WashU: Washington University in St. Louis)H-Index: 22
Last. Andrei G. Vlassenko(WashU: Washington University in St. Louis)H-Index: 22
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Sex differences influence brain morphology and physiology during both development and aging. Here we apply a machine learning algorithm to a multiparametric brain PET imaging dataset acquired in a cohort of 20- to 82-year-old, cognitively normal adults ( n = 205) to define their metabolic brain age. We find that throughout the adult life span the female brain has a persistently lower metabolic brain age—relative to their chronological age—compared with the male brain. The persistence of relative...
There is still disagreement among studies with respect to the magnitude, location, and direction of sex differences of local gray matter volume (GMV) in the human brain. Here, we applied a state-of-the-art technique examining GMV in a well-powered sample (n = 2,838) validating effects in two independent general-population cohorts, age range 21–90 years, measured using the same MRI scanner. More GMV in women than in men was prominent in medial and lateral prefrontal areas, the superior temporal s...
Last. Nicola Toschi(University of Rome Tor Vergata)H-Index: 37
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Abstract Irreversible white matter (WM) damage, including severe demyelination and axonal loss, is a main determinant of long-term disability in multiple sclerosis (MS). Non-invasive detection of changes in microstructural WM integrity in the disease is challenging since commonly used imaging metrics lack the necessary sensitivity, especially in the early phase of the disease. This study aims at assessing microstructural WM abnormalities in early-stage MS by using ultra-high gradient strength mu...
Abstract Myelin breakdown and neural fiber loss occur in aging. This study used white matter tract integrity metrics derived from biophysical modeling using Diffusional Kurtosis Imaging to assess loss of myelin (i.e., extraaxonal diffusivity, radial direction, De,⊥) and axonal density (i.e., axonal water fraction) in cognitively unimpaired older adults. Tract-based spatial statistics and region of interest analyses sought to identify ontogenic differences and age-related changes in white matter ...
#2Simon R. Cox(Edin.: University of Edinburgh)H-Index: 30
Last. Ian J. Deary(Edin.: University of Edinburgh)H-Index: 21
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Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional...
Conventional diffusion-weighted MR imaging techniques provide limited specificity in disentangling disease-related microstructural alterations involving changes in both axonal density and myelination. By simultaneously probing multiple diffusion regimens, multi-shell diffusion MRI is capable of increasing specificity to different tissue sub-compartments and hence separate different contributions to changes in diffusion-weighted signal attenuation. Advanced multi-shell diffusion models impose sig...
#2L. Nabulsi(SC: University of Southern California)H-Index: 1
Last. Paul M. Thompson(SC: University of Southern California)H-Index: 201
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A comprehensive characterization of the brain9s white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter microstructure in a cross-sectional sample of 15,628 adults aged 45-80 years old (47.6% male, 52.4% female). Microstructure was assessed using the following four models: a conventional single-shell model, diffusion tensor imaging (DTI); a more advanc...
Diseases and aging-associated alterations of the nervous system often show sex-specific characteristics. Glial cells play a major role in the endogenous homeostatic response of neural tissue, and sex differences in the glial transcriptome and function have been described. Therefore, the possible role of these cells in the generation of sex differences in pathological alterations of the nervous system is reviewed here. Studies have shown that glia react to pathological insults with sex-specific n...
#1Emilie T. Reas(UCSD: University of California, San Diego)H-Index: 13
#2Donald J. Hagler(UCSD: University of California, San Diego)H-Index: 88
Last. Linda K. McEvoy(UCSD: University of California, San Diego)H-Index: 66
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Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial m...
#2John Plass(UM: University of Michigan)H-Index: 5
Last. Thad A. Polk(UM: University of Michigan)H-Index: 32
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Aging is associated with widespread alterations in cerebral white matter (WM). Most prior studies of age differences in WM have used diffusion tensor imaging (DTI), but typical DTI metrics (e.g., fractional anisotropy; FA) can reflect multiple neurobiological features, making interpretation challenging. Here, we used fixel-based analysis (FBA) to investigate age-related WM differences observed using DTI in a sample of 45 older and 25 younger healthy adults. Age-related FA differences were widesp...
#1Emilie T. Reas(UCSD: University of California, San Diego)H-Index: 13
#2Donald J. Hagler(UCSD: University of California, San Diego)H-Index: 88
Last. Linda K. McEvoy(UCSD: University of California, San Diego)H-Index: 66
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Abstract Cytoarchitectural brain changes within gray matter and fiber tracts during normal aging remain poorly characterized, and it is unclear whether rates and patterns of brain aging differ by sex. This study used restriction spectrum imaging (RSI) to examine associations between age and brain microstructure in 147 community-dwelling participants (aged 56-99). Widespread associations with older age in multiple diffusion compartments, including increased free water, decreased restricted and hi...
Abstract The biophysical modeling efforts in diffusion MRI have grown considerably over the past 25 years. In this review, we dwell on the various challenges along the journey of bringing a biophysical model from initial design to clinical implementation, identifying both hurdles that have been already overcome and outstanding issues. First, we describe the critical initial task of selecting which features of tissue microstructure can be estimated using a model and which acquisition protocol nee...
#2John Plass(UM: University of Michigan)H-Index: 5
Last. Thad A. Polk(UM: University of Michigan)H-Index: 32
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Abstract Older adults tend to perform worse on cognitive, behavioral, motor, and sensory tasks compared to younger adults, and differences in white matter that may be associated with this phenomenon are being actively investigated. Most prior studies of white matter differences between older and younger adults have analyzed diffusion weighted images using diffusion tensor imaging (DTI) analysis. But DTI results can be affected by many different factors (e.g., fiber density, fiber cross-section, ...