Clinical determinants of microvascular perfusion in minor ischemic stroke: evidence from dynamic susceptibility contrast MRI in the ENIGMA cohort

Microvascular dysfunction is increasingly recognized as a key mechanism in cerebrovascular disease, including ischemic stroke and cerebral small vessel disease (cSVD). Dynamic susceptibility contrast (DSC) MRI measures cerebral perfusion and microvascular flow disturbances and allow estimation of their impact on brain oxygenation. In a cohort of patients with acute ischemic stroke or transient ischemic attack, we used contralateral normal-appearing white matter (NAWM) perfusion as a proxy for pre-stroke microvascular status and examined its relation to stroke etiology, cSVD burden, and patient risk factors. Patients ( n = 136) with acute ischemic stroke or transient ischemic attack underwent 3T MRI, including DSC MRI with gradient-echo (GRE) and microvessel-weighted spin-echo (SE) sequences the day after symptom onset. Perfusion and oxygenation metrics, including capillary transit-time heterogeneity (CTH), and estimates of oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) were assessed in contralateral NAWM and compared to TOAST subtype, composite cSVD burden scores, age, sex, and vascular risk factors. The cohort comprised patients with mainly mild strokes (median NIHSS score 3 [IQR 1–5]). Median infarct volume was 0.69 mL (IQR 0.29–3.18), and median cSVD score was 4 (IQR 2–5). Across stroke subtypes, SE-based cerebral blood volume (CBV) ( p = 0.011), cerebral blood flow (CBF) ( p = 0.043), and CMRO₂ ( p = 0.022) in contralateral NAWM were higher in patients with strokes attributed to large artery atherosclerosis. Perfusion metrics were not associated with cSVD burden (all p > 0.2). Higher age and male sex were associated with lower CBF, higher CTH, and lower CMRO 2 (all p < 0.02). Vascular risk factors were associated with distinct microvascular changes as measured by SE-based DCS and less so with GE based DSC MRI. Contralateral NAWM perfusion and oxygenation metrics were not associated with structural cSVD burden and did not show the expected association with small-vessel occlusion. Instead, SE-derived metrics were more closely associated with age, sex, and vascular risk factors, suggesting that contralateral NAWM hemodynamics may reflect broader clinical vascular determinants rather than stroke subtype or cSVD burden alone. ClinicalTrials.gov, NCT06257823. First submitted: 6 February 2024. Retrospectively registered.