Abstract

Task-evoked Blood-oxygenation-level-dependent (BOLD-fMRI) signal activation is widely used to interrogate eloquence of brain areas. However, data interpretation can be improved, especially in regions with absent BOLD-fMRI signal activation. Absent BOLD-fMRI signal activation may actually represent false-negative activation due to impaired cerebrovascular reactivity (BOLD-CVR) of the vascular bed. The relationship between impaired BOLD-CVR and BOLD-fMRI signal activation may be better studied in healthy subjects where neurovascular coupling is known to be intact. Using a model-based prospective end-tidal carbon dioxide (CO2) targeting algorithm, we performed two controlled 3 tesla BOLD-CVR studies on 17 healthy subjects: 1: at the subjects’ individual resting end-tidal CO2 baseline. 2: Around +6.0 mmHg CO2 above the subjects’ individual resting baseline. Two BOLD-fMRI finger-tapping experiments were performed at similar normo- and hypercapnic levels. Relative BOLD fMRI signal activation and t-values were calculated for BOLD-CVR and BOLD-fMRI data. For each component of the cerebral motor-network (precentral gyrus, postcentral gyrus, supplementary motor area, cerebellum und fronto-operculum), the correlation between BOLD-CVR and BOLD-fMRI signal changes and t-values was investigated. Finally, a voxel-wise quantitative analysis of the impact of BOLD-CVR on BOLD-fMRI was performed. For the motor-network, the linear correlation coefficient between BOLD-CVR and BOLD-fMRI t-values were significant (p<0.01) and in the range 0.33–0.55, similar to the correlations between the CVR and fMRI Δ%signal (p<0.05; range 0.34–0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Δ%signal and t-value change between normo- and hypercapnia. Our main finding is that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-CVR and highlights the importance of a complementary BOLD-CVR assessment in addition to a task-evoked BOLD fMRI to identify brain areas at risk for false-negative BOLD-fMRI signal activation.

Highlights

  • Task-evoked blood oxygenation-level dependent functional magnetic resonance imaging (BOLD-fMRI) is based on neurovascular coupling and is widely used to interrogate eloquence of brain areas.[1, 2] Neurovascular coupling is considered to represent the biochemical cascade between neuronal activation and subsequent local cerebral blood flow (CBF) increase.[3]

  • By using a voxel-wise analysis, we found that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-cerebrovascular reactivity (CVR)

  • BOLD parameters used for both BOLD-CVR as well as the task-evoked BOLD-fMRI measurements consisted of axial two dimensional (2D) single-shot EPI sequence planned on the ACPC line plus 20 ̊ voxel size 3×3×3 mm3, acquisition matrix 64x64x35 ascending interleaved slice acquisition, slice gap 0.3 mm, GRAPPA factor 2 with 32 ref. lines, repetition time (TR)/ echo time (TE) 2000/30 ms, flip angle 85 ̊, bandwidth 2368 Hz/Px, Field of View 192x192 mm2

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Summary

Introduction

Task-evoked blood oxygenation-level dependent functional magnetic resonance imaging (BOLD-fMRI) is based on neurovascular coupling and is widely used to interrogate eloquence of brain areas.[1, 2] Neurovascular coupling is considered to represent the biochemical cascade between neuronal activation and subsequent local cerebral blood flow (CBF) increase.[3] This premise, imposes two major challenges for an accurate interpretation of BOLDfMRI studies. The extent and strength of the fMRI signal response to a task-related neuronal activation (for instance finger-tapping) varies considerably between subjects and requires a summation of repeated tests and arbitrary statistical data thresholding. BOLD-fMRI does not directly measure neuronal activity or blood flow, rather it shows the relative change in de-oxyhemoglobin concentration.[4, 5] The intrinsic BOLD-fMRI signal is strongly influenced by CBF, and to a lesser extent changes in metabolism (cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF)).[2]

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