Reliable quantification of BOLD fMRI cerebrovascular reactivity despite poor breath-hold performance

Abstract

Cerebrovascular reactivity (CVR) can be mapped using BOLD fMRI to provide a clinical insight into vascular health that can be used to diagnose cerebrovascular disease. Breath-holds are a readily accessible method for producing the required arterial CO2 increases but their implementation into clinical studies is limited by concerns that patients will demonstrate highly variable performance of breath-hold challenges. This study assesses the repeatability of CVR measurements despite poor task performance, to determine if and how robust results could be achieved with breath-holds in patients. Twelve healthy volunteers were scanned at 3T. Six functional scans were acquired, each consisting of 6 breath-hold challenges (10, 15, or 20 s duration) interleaved with periods of paced breathing. These scans simulated the varying breath-hold consistency and ability levels that may occur in patient data. Uniform ramps, time-scaled ramps, and end-tidal CO2 data were used as regressors in a general linear model in order to measure CVR at the grey matter, regional, and voxelwise level. The intraclass correlation coefficient (ICC) quantified the repeatability of the CVR measurement for each breath-hold regressor type and scale of interest across the variable task performances. The ramp regressors did not fully account for variability in breath-hold performance and did not achieve acceptable repeatability (ICC < 0.4) in several regions analysed. In contrast, the end-tidal CO2 regressors resulted in “excellent” repeatability (ICC = 0.82) in the average grey matter data, and resulted in acceptable repeatability in all smaller regions tested (ICC > 0.4). Further analysis of intra-subject CVR variability across the brain (ICCspatial and voxelwise correlation) supported the use of end-tidal CO2 data to extract robust whole-brain CVR maps, despite variability in breath-hold performance. We conclude that the incorporation of end-tidal CO2 monitoring into scanning enables robust, repeatable measurement of CVR that makes breath-hold challenges suitable for routine clinical practice.

Cerebrovascular Reactivity Mapping: An Evolving Standard for Clinical Functional Imaging

“…[11][12][13] The breath-hold (BH) technique offers a simpler alternative that is easier to implement in the clinical setting and yet can produce similar increases in arterial CO 2 levels and resultant similarly useful BOLD CVR maps as those achieved by using gas-inhalation techniques. 14 This technique involves short-duration BHs, typically in the range of 10 -30 seconds, which alternate with periods of normal breathing.…”

“…Even BHs that are much shorter (eg, as short as 3 seconds) may produce brief states of hypercapnia that result in measurable BOLD signal changes, but the robustness of the BOLD response and the number of voxels in the brain cortex displaying BOLD signal changes increase with the increasing duration of the BH. 13,15 In addition, the reproducibility of such BOLD responses is greater and interscan variability is minimized with longer BH periods. 13,16 While BHs in the range of 20 -30 seconds may be feasible for healthy volunteers, in some patients, such as those with brain tumors, a compromise may be necessary between ideal BH duration and patient comfort/tolerance limits.…”

“…13,15 In addition, the reproducibility of such BOLD responses is greater and interscan variability is minimized with longer BH periods. 13,16 While BHs in the range of 20 -30 seconds may be feasible for healthy volunteers, in some patients, such as those with brain tumors, a compromise may be necessary between ideal BH duration and patient comfort/tolerance limits. Furthermore, healthy volunteer studies have shown that the use of blocks of paced breathing between successive BH blocks provides a more consistent BOLD baseline from which the breath-hold BOLD signal response can be extracted, resulting in more accurate assessment and reduced interscan variability.…”

“…Furthermore, healthy volunteer studies have shown that the use of blocks of paced breathing between successive BH blocks provides a more consistent BOLD baseline from which the breath-hold BOLD signal response can be extracted, resulting in more accurate assessment and reduced interscan variability. 13,17 Other studies have suggested that use of end-expiration BHs results in greater reproducibility than end-inspiration BH techniques because end-expiration offers a more natural resting equilibrium state involving the diaphragm, lungs, and chest wall before initiation of a BH challenge. 13,17 Thomason and Glover 18 have even suggested that the BOLD response resulting from endexpiration BHs is slightly different from that of end-inspiration BHs in that the latter involves more of a biphasic BOLD response, which is less desirable.…”

Reprint of: Minimizing noise in pediatric task-based functional MRI; Adolescents with developmental disabilities and typical development

“…Other methods of motion correction include independent components analysis (ICA; e.g., FMRIB's FIX see SalimiKhorshidi et al, 2014) and multi-echo fMRI (Bright and Murphy, 2013;Kundu et al, 2015). These methods have been shown to separate noise artifact from the BOLD signal.…”