Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and neurotoxic Aβ in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study, we compared cerebral microcirculation in a cohort of AD and mild cognitive impairment (MCI) patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than 2 years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared with controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal, and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.

Quantitative study of the capillaries within the white matter of the Tg2576 mouse model of Alzheimer's disease

“…Moreover, in animal research, it is possible to conduct research in the early stage of AD, which is very important for the prevention of AD. Using dynamic susceptibility contrast magnetic resonance imaging, Eskildsen et al studied microvascular blood flow in white matter without damaging the brain (Eskildsen et al, ). Our stereological vascular study is a quantitative study of the internal structure of blood vessels, which is more reflective of the details of AD‐damaged blood vessels than just local blood flow.…”

August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data

“…Meanwhile, the absence of large vessel changes in Alzheimer's disease (AD) has led most researchers and physicians to discard the notion that vascular disease changes play a role in its etiology -although AD shares most risk factors with cardiovascular disease and stroke. Recently, however, capillary flow disturbances, indicative of insufficient tissue O 2 levels in brain tissue, were demonstrated in AD patients (Eskildsen et al 2017;Nielsen et al 2017), illustrating how our incomplete understanding of O 2 transport in tissue has misguided our approach to understand fundamental disease mechanisms.…”

Accelerated whole‐brain perfusion imaging using a simultaneous multislice spin‐echo and gradient‐echo sequence with joint virtual coil reconstruction

“…In addition, whole‐brain coverage advances the ability to visualize tumors outside of the narrower slice coverage that is typically used for DSC imaging, covering only the area surrounding a known tumor location, which could be difficult when imaging particularly large gliomas or capturing metastases in multiple locations in the brain. Whole‐brain coverage is also applicable in other areas of research with DSC, such as Alzheimer’s disease, where it is desirable to capture hypoperfusion across the entire brain . Supporting Information Table demonstrates the tradeoffs in resolution, slice coverage, SNR, and quantitative mapping from using a more conventional single‐echo DSC acquisition compared with the SAGE acquisition, with and without slice acceleration.…”