Measuring vascular reactivity with breath-holds after stroke: a method to aid interpretation of group-level BOLD signal changes in longitudinal fMRI studies.

Blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breath-hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri-infarct tissue, both sub-acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group-level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold-based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity.

Geranmayeh F ，Wise RJ ，Leech R ，Murphy K ... -  《-》

Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.

Pillai JJ ，Zacà D 《-》

Comparing end-tidal CO(2), respiration volume per time (RVT), and average gray matter signal for mapping cerebrovascular reactivity amplitude and delay with breath-hold task BOLD fMRI.

Cerebrovascular reactivity (CVR), defined as the cerebral blood flow response to a vasoactive stimulus, is an imaging biomarker with demonstrated utility in a range of diseases and in typical development and aging processes. A robust and widely implemented method to map CVR involves using a breath-hold task during a BOLD fMRI scan. Recording end-tidal CO2 (PETCO2) changes during the breath-hold task is recommended to be used as a reference signal for modeling CVR amplitude in standard units (%BOLD/mmHg) and CVR delay in seconds. However, obtaining reliable PETCO2 recordings requires equipment and task compliance that may not be achievable in all settings. To address this challenge, we investigated two alternative reference signals to map CVR amplitude and delay in a lagged general linear model (lagged-GLM) framework: respiration volume per time (RVT) and average gray matter BOLD response (GM-BOLD). In 8 healthy adults with multiple scan sessions, we compare spatial agreement of CVR maps from RVT and GM-BOLD to those generated with PETCO2. We define a threshold to determine whether a PETCO2 recording has "sufficient" quality for CVR mapping and perform these comparisons in 16 datasets with sufficient PETCO2 and 6 datasets with insufficient PETCO2. When PETCO2 quality is sufficient, both RVT and GM-BOLD produce CVR amplitude maps that are nearly identical to those from PETCO2 (after accounting for differences in scale), with the caveat they are not in standard units to facilitate between-group comparisons. CVR delays are comparable to PETCO2 with an RVT regressor but may be underestimated with the average GM-BOLD regressor. Importantly, when PETCO2 quality is insufficient, RVT and GM-BOLD CVR recover reasonable CVR amplitude and delay maps, provided the participant attempted the breath-hold task. Therefore, our framework offers a solution for achieving high quality CVR maps in both retrospective and prospective studies where sufficient PETCO2 recordings are not available and especially in populations where obtaining reliable measurements is a known challenge (e.g., children). Our results have the potential to improve the accessibility of CVR mapping and to increase the prevalence of this promising metric of vascular health.

Zvolanek KM ，Moia S ，Dean JN ，Stickland RC ，Caballero-Gaudes C ，Bright MG ... -  《-》

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

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 3 T. 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.

Bright MG ，Murphy K 《-》

Fine tuning breath-hold-based cerebrovascular reactivity analysis models.

van Niftrik CH ，Piccirelli M ，Bozinov O ，Pangalu A ，Valavanis A ，Regli L ，Fierstra J ... -  《Brain and Behavior》