Visualization of Altered Neurovascular Coupling in Chronic Stroke Patients using Multimodal Functional MRI

Abstract

Evaluation of cortical reorganization in chronic stroke patients requires methods to accurately localize regions of neuronal activity. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is frequently employed; however, BOLD contrast depends on specific coupling relationships between the cerebral metabolic rate of oxygen (CMRO 2 ), cerebral blood flow (CBF), and volume (CBV), which may not exist following stroke. The aim of this study was to understand whether CBF-weighted (CBFw) and CBV-weighted (CBVw) fMRI could be used in sequence with BOLD to characterize neurovascular coupling mechanisms poststroke. Chronic stroke patients (n = 11) with motor impairment and age-matched controls (n = 11) performed four sets of unilateral motor tasks (60 seconds/30 seconds off/on) during CBFw, CBVw, and BOLD fMRI acquisition. While control participants elicited mean BOLD, CBFw, and CBVw responses in motor cortex (P < 0.01), patients showed only mean changes in CBF (P < 0.01) and CBV (P < 0.01), but absent mean BOLD responses (P = 0.20). BOLD intersubject variability was consistent with differing coupling indices between CBF, CBV, and CMRO 2 . Thus, CBFw and/or CBVw fMRI may provide crucial information not apparent from BOLD in these patients. A table is provided outlining distinct vascular and metabolic uncoupling possibilities that elicit different BOLD responses, and the strengths and limitations of the multimodal protocol are summarized.

Neurovascular Regulation in the Ischemic Brain

“…Similarly, wrist movement failed to increase the BOLD signal in the primary motor cortex in chronic stroke patients (13), suggesting impaired functional hyperemia in regions with increased functional activity. However, when cerebral blood flow and blood volume were assessed in response to functional activation using the more direct methods of arterial spin labeling (ASL) and vascular-space-occupancy-fluid attenuated inversion recovery, functional hyperemia was, in fact, maintained in the motor cortex after stroke (13). The reasons for the discrepancy between the results obtained with BOLD and ASL remain unclear.…”

Functional magnetic resonance imaging in chronic ischaemic stroke

“…In the remaining 75% of patients, who exhibited some BOLD response, no correlation was found between the amplitude of the BOLD response and the degree of hypercapnic reactivity of the major arterial vessels, though impaired microvascular reactivity was thus not excluded. Moreover, Blicher et al [31] observed no BOLD signal change, on average, in M1 in response to unilateral isolated wrist extension-flexion in patients with residual paralysis, yet arterial spin labelling (ASL) and VASO-FLAIR (vascular-spaceoccupancy fluid attenuated inversion recovery) showed this task elicited CBF and CBV increases that were indistinguishable from those observed in control subjects [31].…”

Neurovascular coupling in humans: Physiology, methodological advances and clinical implications

“…69 For example, individuals with ischemic stroke can exhibit a blunted, exaggerated or reduced functional MRI BOLD signal during visual stimulation, with exaggerated or blunted hyperemia. 69 Although these data indicate a mismatch between CBF delivery and oxygenation extraction/metabolism, 69 the mechanisms explaining the variability in the functional MRI BOLD signal responses during visual stimulation are unknown.…”