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Biomedical Imaging and Instrumentation

Evaluating the Relationship between White Matter Hyperintensities and Cerebrovascular Reactivity in White Matter Regions of Elderly Participants

(D-157) Evaluating the Relationship between White Matter Hyperintensities and Cerebrovascular Reactivity in White Matter Regions of Elderly Participants

Saturday, October 14, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row D - Poster # 157

Presenting Author(s)

CH

Claire M. Hsu (she/her/hers)

Undergraduate Researcher
Department of Biomedical Engineering, University of California Davis
Davis, California, United States

Co-Author(s)

QL

Quimby N. Lee

Graduate Researcher
Department of Neurology, University of California Davis, United States
GW

Gregory Wheeler

Graduate Researcher
Department of Biomedical Engineering, University of California Davis, United States

Primary Investigator(s)

AF

Audrey P. Fan

Assistant Professor
Department of Biomedical Engineering, University of California Davis; Department of Neurology, University of California Davis Health, United States

Introduction:: This abstract best fits the Magnetic Resonance Imaging and Applications (MRI) sub-tract.

White matter hyperintensities (WMH) are regions located in white matter of the brain that appear unexpectedly bright in fluid-attenuated inversion recovery (FLAIR) MRI scans. Despite being present in as many as 95% of individuals fifty years and older,1 WMH pathogenesis has been unclear. However, recent studies have shown that WMH are indicative of vascular damage. Another indicator of vascular health is cerebrovascular reactivity (CVR), or the ability of blood vessels to dilate in response to vasoactive stimuli. In this study, we measure CVR to investigate WMH’s effect on cerebrovascular health in white matter. CVR is calculated through the blood-oxygen level dependent (BOLD) signal of functional magnetic resonance imaging (fMRI). A limitation of traditional CVR assessment is the requirement of vasoactive stimuli, such as CO2, which adds burden to scan acquisition. To circumvent this gas challenge, resting state CVR (RS-CVR), which relies on intrinsic fluctuations in the BOLD signal, can be used to calculate relative CVR (rCVR) for each voxel compared to the whole-brain mean. Although both WMH burden and CVR reduction are indicators of cerebrovascular health in aging, their relationship in specific white matter tracts and their combined effects on cognitive function is poorly understood. In this study, we investigate this relationship by correlating percent WMH (%WMH) to rCVR in specific white matter tracts. We hypothesize that %WMH is inversely proportional to rCVR in white matter tracts.

Materials and Methods:: A T1-weighted structural scan, 8-minute resting state fMRI (rs-fMRI) scan, and T2 FLAIR scan were obtained for each of the 120 participants (64-97 years, 83 female) from the Alzheimer's Disease Research Center at UC Davis. Of the 120 participants, 97 were cognitively normal, 18 were mildly impaired, and 5 were diagnosed with dementia. The T1-weighted and rs-fMRI scans were preprocessed with standard steps of brain extraction, segmentation, motion correction, and registration of the fMRI image to structural and MNI brain template space. In addition, the resting state BOLD images were smoothed with a Gaussian kernel of 8mm. Relative CVR maps were generated using a voxelwise regression of the gray matter BOLD signal as a surrogate for the CO2 time series during natural breathing.2 The maps were then transformed from rs-fMRI space into MNI space using the registration from preprocessing. Finally, we calculated the average rCVR values for specific white matter tracts identified through the Johns Hopkins University atlas. To determine %WMH for each participant, the T2 FLAIR scans were segmented into gray matter, white matter, cerebrospinal fluid, and WMH regions through a semi-automated procedure described in previous studies.3,4 %WMH was then calculated by dividing the number of WMH voxels by the total number of brain voxels and multiplying that fraction by 100%. For analysis, %WMH was log-transformed to ensure the values were normally distributed. Linear regression was used to correlate the log(%WMH) for each participant to the rCVR values of the 20 white matter tracts.

Results, Conclusions, and Discussions:: Out of the 20 white matter tracts, we observed a strong negative trend (p< 0.1) between %WMH and rCVR in the left cingulate gyrus (m=-0.024, p=0.082), right cingulate gyrus (m=-0.030, p=0.074), and left uncinate fasciculus (m=-0.034, p=0.082). This finding aligns with our hypothesis that having a greater %WMH corresponds to a lower rCVR value. In addition, the identified white matter areas have previously shown vulnerability to WMH lesions and are involved in functional networks that change in aging and cognitive impairment, which our results associate with vascular injury (reduced rCVR).5 In the future, we will extend our linear models to account for age and cognitive status. Furthermore, correlating tract-specific WMH burden to rCVR may also reveal a more detailed relationship between the two measures. Overall, our work will strengthen our understanding of the pathogenesis of WMH and cerebrovascular diseases.

Acknowledgements (Optional): :

References (Optional): :

Ni L, Zhang B, Yang D, et al. Lower Cerebrovascular Reactivity Contributed to White Matter Hyperintensity‐related Cognitive Impairment: A Resting-State Functional MRI Study. Journal of Magnetic Resonance Imaging. 2020;53(3):703-711. doi:10.1002/jmri.27376

Bhogal AA. Medullary vein architecture modulates the white matter bold cerebrovascular reactivity signal response to CO2: Observations from high-resolution T2* weighted imaging at 7t. NeuroImage. 2021;245:118771. doi:10.1016/j.neuroimage.2021.118771

DeCarli C, Maisog J, Murphy DG, Teichberg D, Rapoport SI, Horwitz B. Method for quantification of brain, ventricular, and subarachnoid CSF volumes from Mr Images. Journal of Computer Assisted Tomography. 1992;16(2):274-284. doi:10.1097/00004728-199203000-00018

DeCarli C, Murphy DGM, Tranh M, et al. The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology. 1995;45(11):2077-2084. doi:10.1212/wnl.45.11.2077

Seiler S, Fletcher E, Hassan-Ali K, et al. Cerebral tract integrity relates to white matter hyperintensities, Cortex Volume, and cognition. Neurobiology of Aging. 2018;72:14-22. doi:10.1016/j.neurobiolaging.2018.08.005