Quantifying neuroinflammation within deep gray matter in small vessel disease using diffusion tensor based free-water imaging: a longitudinal study.

Purpose: Employing free water (FW) imaging, a cutting-edge diffusion MRI technique, we assessed neuroinflammation within deep gray matter (DGM) in small vessel disease (SVD) over 1-2 years.

Method: One hundred and seventy SVD patients and 21 healthy controls (HCs) underwent MRI scans and neuropsychological evaluations at baseline. These patients were then categorized into two groups: 67 displayed no cognitive impairment (NCI), while 103 exhibited vascular mild cognitive impairment (VaMCI). A follow-up study 1-2 years later included 23 from the NCI group and 28 from the VaMCI group. Calculation of FW values within DGM facilitated both cross-sectional and longitudinal analysis, revealing partial correlations between FW value changes and cognitive function alternations.

Results: Baseline examinations disclosed significant differences in DGM FW values among the three participant groups. We found increased mean FW values in the left pulvinar (Pul), bilateral lateral nuclei (LN) and bilateral internal medullary lamina of the thalamus in VaMCI participants compared with their NCI counterparts in longitudinal analysis. Notably, negative associations emerged between the FW value changes in the left Pul and the right LN of the thalamus and MoCA score changes in the VaMCI group over 1-2 years.

Conclusions: These findings support the hypothesis that increased FW value is present at the preclinical stage of SVD and remains persistent during the early course of the disease, potentially acting as the biomarker for the mechanism of underlying cognitive decline in SVD.