Abstract

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is commonly used to measure cerebrovascular reactivity (CVR), which can convey insightful information about neurovascular health. Breath-holding (BH) has been shown to be a practical vasodilatory stimulus for measuring CVR in clinical settings. The conventional BOLD fMRI approach has some limitations, however, such as susceptibility-induced signal dropout at air tissue interfaces and low BOLD sensitivity especially in areas of low . These drawbacks can potentially be mitigated with multi-echo sequences, which acquire several images at different echo times in one shot. When combined with multiband techniques, high temporal resolution images can be acquired. This study compared an advanced multiband multi-echo (MBME) echo planar imaging (EPI) sequence with an existing multiband single-echo (MB) sequence to evaluate the repeatability and sensitivity of BH activation and CVR mapping. Images were acquired from 28 healthy volunteers, of which 18 returned for repeat imaging. Both MBME and MB data were pre-processed using both standard and advanced denoising techniques. The MBME data was further processed by combining echoes using a -weighted approach and denoising using multi-echo independent component analysis. BH activation was calculated using a general linear model and the respiration response function. CVR was computed as the percent change related to the activation. To account for differences in CVR related to TE, relative CVR (rCVR) was computed and normalized to the mean gray matter CVR. Test–retest metrics were assessed with the Dice coefficient, rCVR difference, within subject coefficient of variation, and the intraclass correlation coefficient. Our findings demonstrate that rCVR for MBME scans were significantly higher than for MB scans across most of the gray matter. In areas of high susceptibility-induced signal dropout, however, MBME rCVR was significantly less than MB rCVR due to artifactually high rCVR for MB scans in these regions. MBME rCVR showed improved test–retest metrics compared with MB. Overall, the MBME sequence displayed superior BOLD sensitivity, improved specificity in areas of signal dropout on MBME scans, enhanced reliability, and reduced variability across subjects compared with MB acquisitions. Our results suggest that the MBME EPI sequence is a promising tool for imaging CVR.

Highlights

  • Blood oxygen level-dependent (BOLD) functional MRI is commonly used to derive cerebrovascular reactivity (CVR), an assessment of the responsiveness of blood vessels in the brain to vasoactive stimuli

  • The estimated signal intensity ratio between the multiband multi-echo (MBME) and multiband single-echo (MB) scans based on TR and flip angle (FA) and calculated using Eq 1 was 1.18 for T1 = 1.3 s

  • The higher TR and optimized FA for the MBME scans resulted in an expected 1.18× SNR advantage over the MB scans assuming noise was equivalent

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Summary

Introduction

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is commonly used to derive cerebrovascular reactivity (CVR), an assessment of the responsiveness of blood vessels in the brain to vasoactive stimuli. The breath-holding (BH) approach has been shown to be reliable and produces comparable CVR values (Kastrup et al, 2001; Kannurpatti and Biswal, 2008; Urback et al, 2017) It does not require the extra equipment needed for gas inhalation, which is not available in clinical settings at all institutions (Liu et al, 2019). Previous studies have demonstrated regional differences in CVR that tend to vary on an individual basis (Yezhuvath et al, 2009; Catchlove et al, 2018) This intrasubject variation can be due to age or disease-related physiological changes such as vascular stiffness or metabolic responses (Ances et al, 2009). It is important to understand the normal inter- and intra-subject variability to determine what constitutes a significant change between subjects or in the same subject over time

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