Biology subjects

Chad, J. A.

Publications and source records attributed to Chad, J. A..

4 recordsLinked to original sources

bioRxiv2022

Sensitivity of diffusion-tensor and correlated diffusion imaging to white-matter microstructural abnormalities: application in COVID-19

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion MRI methods for detecting such effects. In this work, the sensitivities of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at baseline and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in water diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a sensitive single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

biophysics↗

bioRxiv2022

Is adiposity associated with white matter microstructural health and intelligence differently in men and women?

The role of vascular risk in age-related brain degeneration has long been the subject of intense study. As a sub-category of vascular risk, obesity has an increasingly recognized role in influencing brain health and health-care strategies, but its association with brain health remains under-studied. Notably, no prior study has addressed sex differences in the association between adiposity and white-matter microstructural integrity, an important early marker of brain degeneration, despite known sex differences in fat storage and usage. This study focuses on the associations between adiposity (abdominal fat ratio: AFR, and liver proton density fat fraction: PDFF) and brain microstructural health (measures of white-matter microstructure using diffusion-tensor imaging, DTI). We found that fluid intelligence and reaction time are indeed associated with body fat differently in men and women. We also found significant differences in the associations of AFR with DTI metrics between sexes. These sex differences are mirrored in the associations of SBP and age with DTI metrics. Moreover, these sex differences in the AFR and SBP associations with DTI metrics persist when controlling for age. Taken together, these findings suggest that there are inherent sex-driven differences in how brain health is associated with vascular risk factors such as obesity.

systems biology↗

bioRxiv2021

Lower Aβ-PET signal in white matter lesions relates to higher extracellular free water in mixed small vessel disease and Alzheimer's pathology

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (A{beta}-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered A{beta}-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to A{beta}-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in A{beta}-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in A{beta}-PET related more closely to higher cortical A{beta} (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and A{beta}-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.

neuroscience↗

bioRxiv2021

White matter microstructural integrity across the adult lifespan: Combined perspective of diffusion tensor and kurtosis imaging

Studies of healthy brain aging have reported diffusivity patterns associated with white matter degeneration using diffusion tensor imaging (DTI), which assumes that diffusion measured at the typical b-value (approximately 1000 s/mm2) is Gaussian. Diffusion kurtosis imaging (DKI) is an extension of DTI that measures non-Gaussian diffusion (kurtosis) to better capture microenvironmental changes by incorporating additional data at a higher b-value. In this study, using UK Biobank data (b values of 1000 and 2000 s/mm2), we investigate (1) the extent of novel information gained from adding diffusional kurtosis to diffusivity observations in aging, and (2) how conventional DTI metrics in aging compare with diffusivity metrics derived from DKI, which are corrected for kurtosis. We find a general pattern of lower kurtosis alongside higher diffusivity among older adults. We also find differences between diffusivity metrics derived from DTI and DKI, emphasizing the importance of accounting for non-Gaussian diffusion. This work highlights the utility of measuring diffusional kurtosis as a simple addition to conventional diffusion imaging of aging.

neuroscience↗