Association between free water and longitudinal dynamics of recent small subcortical infarcts: a study based on diffusion tensor imaging

The mechanisms underlying the different morphological evolution of recent small subcortical infarcts (RSSIs)-ranging from cavitation to complete disappearance-remain incompletely understood. Free water (FW), derived from diffusion tensor image, has emerged as a sensitive marker reflecting various pathophysiological processes that may influence RSSI evolution. This study aimed to investigate whether baseline FW measures and their longitudinal changes are associated with the morphological evolution of RSSIs. We prospectively enrolled 42 RSSI patients who underwent comprehensive clinical assessments and magnetic resonance imaging scans at baseline and the 1-year follow-up. FW values were calculated for the lesion, ipsilesional white matter (WM), and contralesional WM, as well as the longitudinal changes in FW within ipsilesional and contralesional WM. Linear regression analyses were performed to examine the associations between FW measures and RSSI cavitation, as well as between cavitation and long-term changes in functional and cognitive outcomes. At the 1-year follow-up, 86 % of RSSIs showed some degree of cavitation and 14 % showed complete disappearance on 3D T1 sequence, with a median cavitation proportion of 10 %. We found that higher baseline ipsilesional WM FW was significantly associated with a greater proportion of RSSI cavitation (β = 0.459, p = 0.015). However, cavity formation was not correlated with changes in functional or cognitive outcomes at the 1-year follow-up. Our findings suggest that baseline ipsilesional WM FW may serve as a sensitive imaging biomarker associated with cavity formation in RSSIs. Given the exploratory nature of this study, future research involving larger sample sizes and longer follow-up periods is needed to further elucidate the relationship between cavity formation and clinical outcomes.