Reduced CMRO₂ and cerebrovascular reserve in patients with severe intracranial arterial stenosis: a combined multiparametric qBOLD oxygenation and BOLD fMRI study

Abstract

Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO2 ) and cerebral metabolic rate of oxygen (CMRO2 ). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO2 and CMRO2 ), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO2 in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well-correlated with the amplitude of the CMRO2 deficit. The altered CMRO2 suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty-stenting.

Keywords: BOLD fMRI; brain; cerebral metabolic rate of oxygen (CMRO2); cerebrovascular reserve; hypercapnia; intracranial arterial stenosis; microvasculature; perfusion; stroke; tissular oxygen saturation (StO2).

Figure 1

Diagram of the acquisition and processing schemes to obtain CVR, perfusion, and oxygenation maps. FLAIR, fluid attenuated inversion recovery; TOF, time of flight; BOLD, blood oxygen level dependent; MSME, multi spin‐echo; MGE3D, 3D multi gradient echo; SPM, statistical parametric mapping; CVR, cerebral vasoreactivity; CBV, cerebral blood volume; CBF, cerebral blood flow; MTT, mean transit time; Tmax, time‐to‐maximum; StO₂, tissular oxygen saturation; CMRO₂, cerebral metabolic rate of oxygen; Gd, gadolinium‐DOTA; Hct, hematocrit; Δχ ₀, change in magnetic susceptibility between oxy and deoxyhemoglobin; Ca, arterial oxygen content. CBV and CBF are obtained from the basal perfusion study. StO₂ is derived from R ${R^{\prime }}_2$ and CBV. CMRO₂ is derived from StO₂ and CBF. CVR is an independent estimate.

Figure 2

Regressor used for fMRI analyses based on mean EtCO₂ variation time courses during hypercapnia (green line). Percentage of BOLD signal averaged over three blocks. Mean BOLD signal time courses of MCA territories ipsilateral and contralateral to the SIAS were represented by red and blue lines, respectively. Both amplitude and initial slope of the BOLD time course decreased in the MCA territory ipsilateral to the SIAS.

Figure 3

(a) CBF, (b) CBV, (c) MTT, (d) Tmax, (e) CVR, and (f) CMRO₂ obtained from the SIAS ipsilateral and the contralateral MCA territories and averaged across patients (n = 12) (mean ± SD).

Figure 4

(a) LI_MCA_StO₂ versus LI_MCA_CBF, (b) LI_MCA_StO₂ versus LI_MCA_CVR, (c) LI_MCA_CMRO₂ versus LI_MCA_CBF, and (d) LI_MCA_CMRO₂ versus LI_MCA_CVR (n = 12). StO₂, tissular oxygen saturation; CBF, cerebral blood flow; CMRO₂, cerebral metabolic rate of oxygen; CVR, cerebrovascular reserve; LI_MCA, laterality indices in MCA territories. Each triangle, diamond and square represents patient with right (MCA/ICA), Left (MCA/ICA) or bilateral (MCA/ICA) stenosis, respectively.

Figure 5

Illustrative individual maps of Patient #12 (upper row, a–f) and Patient #4 (lower row, g–l), representing FLAIR (a, g), TOF with stenosis (white arrows) (b, h), ROIs used for delineate the MCA territories overlaid onto axial T ₁‐WI (c, i), BOLD response to hypercapnia (d, j), CMRO₂ (e, k), and CBF (f, l). Patient #12 had a combined reduction of CBF, CVR, and CMRO₂ in the left MCA territory downstream a left MCA SIAS, whereas Patient #4 with a left ICA SIAS had symmetrical values.