Spatial Signature of White Matter Hyperintensities in Stroke Patients.

Markus D Schirmer,Natalia S Rost,Steven M Greenberg,Lisa Cloonan,Mark R Etherton,Panagiotis Fotiadis,Ona Wu,Anand Viswanathan,Anne-Katrin Giese

doi:10.3389/fneur.2019.00208

Abstract

Purpose: White matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke (AIS).Materials and Methods: We created a novel age-appropriate high-resolution brain template and anatomically delineated the cerebral vascular territories. We used WMH masks derived from the clinical T2 Fluid Attenuated Inverse Recovery (FLAIR) MRI scans and spatial normalization of the template to discriminate between WMH volume within each subject's anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories. Linear regression modeling including age, sex, common vascular risk factors, and TOAST stroke subtypes was used to assess for spatial specificity of WMH volume (WMHv) in a cohort of 882 AIS patients.Results: Mean age of this cohort was 65.23 ± 14.79 years, 61.7% were male, 63.6% were hypertensive, 35.8% never smoked. Mean WMHv was 11.58c ± 13.49 cc. There were significant differences in territory-specific, relative to global, WMH burden. In contrast to PCA territory, age (0.018 ± 0.002, p < 0.001) and small-vessel stroke subtype (0.212 ± 0.098, p < 0.001) were associated with relative increase of WMH burden within the anterior (ACA and MCA) territories, whereas male sex (−0.275 ± 0.067, p < 0.001) was associated with a relative decrease in WMHv.Conclusions: Our data establish the spatial specificity of WMH distribution in relation to vascular territory and risk factor exposure in AIS patients and offer new insights into the underlying pathology.

Highlights

White matter hyperintensity (WMH) is an important and widely studied radiographic phenotype [1]
We investigate the efficacy of this model, compared to a baseline model, where the WMHvrel is solely explained by volume of the territory in subject space (Vterr), given by
Final Cohort and Territorial WMH Burden Characterization Each subject is non-linearly registered to the 3D-Fluid Attenuated Inverse Recovery (FLAIR) template and the vascular territory map transformed into low-resolution subject space

Summary

Introduction

White matter hyperintensity (WMH) is an important and widely studied radiographic phenotype [1]. Spatial Signature of WMH burden can be summarized as WMH volume (WMHv) [1,2,3] It has been shown, that WMHv presents an accurate and uniform way of quantifying this phenotype in clinical populations, such as acute ischemic stroke (AIS) patients [4]. Summarizing the burden on such a high level, i.e., total WMHv, eliminates potential spatial specificity, which in turn may provide insight with regard to underlying vascular pathology and disease progression. The anterior supratentorial circulation is comprised of the anterior (ACA) and middle cerebral artery (MCA), while the posterior cerebral artery (PCA) supplies the posterior supratentorial vascular area. Infratentorial structures receive their blood supply through the posterior circulation. Large-scale analysis of WMH burden for each vascular territory is limited, as manual assessment and differentiation of individual vascular territories is time consuming and results in inter-rater variations

Methods

Results

Conclusion