Friday, May 9, 2025
5/9/2025
Quantitative clinical imaging of demyelination and remyelination in ischemic stroke - Myelin is a major structural component of the brain playing a vital role for its proper function. Demyelination is commonly observed in numerous neurological conditions where it can be either a primary pathological substrate or a direct consequence of damage to axons, neurons, or oligodendroglia caused by various injuries. Recent animal studies indicate that demyelination is an important component of the sequence of pathological events in ischemic stroke. After initial myelin damage, infarcted brain tissue undergoes either progressive demyelination and necrosis or remyelination accompanied by axonal remodeling. Current knowledge about myelin damage and repair in stroke is exclusively based on animal models. We propose a clinical study that aims to a) demonstrate the feasibility of quantifying myelin loss and recovery in stroke patients; b) establish a relationship of demyelination and remyelination with various clinical factors; and c) identify associations of demyelination and subsequent remyelination with functional recovery after stroke. The study is driven by the overarching hypothesis that demyelination in stroke provides an indicator of the extent of overall tissue injury, and, vice versa, brain tissue repair after stroke can be monitored by quantifying remyelination. Demyelination and remyelination in stroke can be assessed with high specificity and sensitivity using a novel quantitative magnetic resonance imaging (MRI) technique named single-point macromolecular proton fraction (MPF) mapping. This method has been extensively validated by histology in animal models and demonstrated promising results in human studies of neurological diseases and brain development. As a clinically-targeted quantitative myelin imaging modality, MPF mapping offers a number of advantages including fast acquisition, independence of magnetic field strength, insensitivity to changes in magnetic relaxation caused by iron deposition, high reproducibility, and straightforward implementation in a clinical setting. In the proposed study, we will further improve the MPF mapping method by accelerating acquisition and introducing a novel reconstruction algorithm that computes absolute macromolecular proton concentration (MPC) to eliminate the confounding effect of edema on MPF. Whole-brain MPF mapping protocols with less than 3 minutes total scan time will be implemented for the most widely used clinical MRI platforms based on unmodified manufactures’ pulse sequences. We will prospectively recruit acute and sub-acute ischemic stroke patients during inpatient treatment and conduct follow-up examinations for six months. Based on longitudinal quantitative myelin assessment using MPF/MPC and a series of clinical outcome measures in several functional domains, the following hypotheses will be tested: 1) MPF/MPC is capable of detecting remyelination during post-stroke brain tissue recovery; 2) an extent of demyelination at baseline and/or subsequent remyelination observed longitudinally is associated with outcomes of rehabilitation; and 3) inclusion of quantitative myelin measures into predictive statistical models improves prognosis of post-stroke rehabilitation.
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