Within-lesion heterogeneity of subcortical DWI lesion evolution, and stroke outcome: A voxel-based analysis

Abstract

The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline (n = 45), six months (n = 45), and three years (n = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, p = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.

Keywords: Clinical outcome; diffusion tensor imaging; free water; stroke; subcortical infarction.

Figure 1.

Heterogeneity of tissue fate within a DWI lesion followed over six months. Baseline (left) and follow-up images (right) of an example DWI lesion. The margin was automatically identified on baseline DWI (trace image) and is marked by a black line. Voxels within this margin were classified into the following three classes using images obtained six months post-stroke. C: cavitation (red); H: T2 hyperintense (green); N: normal (blue).

Figure 2.

Tissue fate at six months post-stroke. Proportions of DWI lesion voxels appearing cavitated (C), hyperintense (H), and normal (N) six months post-stroke. (a) Results for individual DWI lesions (n = 59). Lesions are arranged from left to right by decreasing extent of cavitation. (b) Boxplots for the whole sample of DWI lesions.

Figure 3.

The extent of cavitation predicts clinical outcome. Swarm plots showing the distribution of modified Rankin scale scores at follow-up plotted against the proportion of DWI lesion voxels that turned into a cavitation at six months post-stroke. Vertical bars represent median values.

Figure 4.

DWI lesion volume at baseline predicts the extent of cavitation at six months post-stroke.

Figure 5.

Diffusion measures at baseline predict tissue fate. Boxplots showing average values for mean diffusivity (MD, panel a), free water corrected tissue MD (MDt, panel b), and free water fraction (panel c) at baseline stratified according to tissue fates at six months post-stroke (C: cavitation; H: hyperintense; N: normal). Diffusion characteristics in contralateral control regions (Con) are shown for comparison.