In Vivo Quantification of Myelin Injury Following Ischemic Stroke.

Abstract

Purpose: Ischemic stroke involves substantial myelinated white matter injury, a key cause of long-term neurological deficits. However, conventional MRI often lacks sufficient sensitivity and specificity to detect myelin pathology and resolve lesional heterogeneity, limiting accurate correlation with clinical outcomes and prognostic assessment. To address this limitation, we recently developed a myelin-targeted PET radiotracer, [¹¹C]MeDAS, which enables in vivo characterization of myelin integrity with high sensitivity and specificity. To establish its utility in ischemic stroke, we conducted a translational imaging study across species.

Procedures: Dynamic [¹¹C]MeDAS-PET/CT imaging, incorporating perfusion correction, was performed sequantially in a rodent middle cerebral artery occlusion (MCAO) model, a rhesus monkey with spontaneous ischemic stroke, and a cohort of six patients with acute ischemic stroke.

Results: In MCAO rats, tracer uptake was significantly reduced in the lesioned hemisphere (SUV ratio: 0.64 ± 0.08, P < 0.001), closely correlating with histological myelin loss. In the non-human primate, infarcted regions exhibited up to 60% SUV reduction in SUV, while stroke patients demonstrated 26-43% lower uptake in infarct cores. Notably, these reductions persisted after perfusion correction. Furthermore, voxel-level analyses revealed pathological heterogeneity within lesions that appeared homogeneous on MRI.

Conclusions: This translational study in rodent model, non-human primates, and human patients demonstrates that [¹¹C]MeDAS-PET is a promising molecular imaging approach for assessing tissue alterations following ischemic stroke. These findings warrant further investigation of [¹¹C]MeDAS-PET as an imaging marker for ischemic stroke.