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Mapping white matter diffusion and cerebrovascular reactivity in carotid occlusive disease

Objective: To characterize the relationship between cerebrovascular reactivity (CVR) and white matter (WM) diffusion in patients with internal carotid artery (ICA) occlusive disease. Methods: In this exploratory observational study, 41 patients with severe stenosis or occlusion of the extracranial ICA and 12 healthy control subjects underwent CVR mapping using the fMRI response to hypercapnia. Conventional anatomic and diffusion-weighted MRI sequences were used to calculate maps of the apparent diffusion coefficient (ADC) and to exclude areas of previous ischemic injury. In all subjects, ADC was compared between WM with positive and negative CVR. In 27 patients with unilateral ICA involvement, ADC and CVR were compared between ipsilateral and contralateral WM while covarying for relevant clinical risk factors. Results: In patients with bilateral disease and in the ipsilateral hemisphere of patients with unilateral disease, negative CVR was associated with increased WM ADC (p < 0.01 and p < 0.005, respectively). In patients with unilateral disease, the ipsilateral CVR deficit was correlated with the degree of hemispheric WM ADC elevation (p < 0.005). ADC elevation remained significant after correction for potential confounding risk factors. Conclusions: CVR impairment is associated with ADC elevation in normal-appearing WM of patients with severe stenosis or occlusion of the extracranial ICA. This finding is consistent with the presence of early, low-grade ischemic injury.