title: Cerebrovascular reactivity mapping without gas challenges.
abstract: Cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or constrict, has been shown to provide valuable information in the diagnosis and treatment evaluation of patients with various cerebrovascular conditions. CVR mapping is typically performed using hypercapnic gas inhalation as a vasoactive challenge while collecting BOLD images, but the inherent need of gas inhalation and the associated apparatus setup present a practical obstacle in applying it in routine clinical use. Therefore, we aimed to develop a new method to map CVR using resting-state BOLD data without the need of gas inhalation. This approach exploits the natural variation in respiration and measures its influence on BOLD MRI signal. In this work, we first identified a surrogate of the arterial CO2fluctuation during spontaneous breathing from the global BOLD signal. Second, we tested the feasibility and reproducibility of the proposed approach to use the above-mentioned surrogate as a regressor to estimate voxel-wise CVR. Third, we validated the "resting-state CVR map" with a conventional CVR map obtained with hypercapnic gas inhalation in healthy volunteers. Finally, we tested the utility of this new approach in detecting abnormal CVR in a group of patients with Moyamoya disease, and again validated the results using the conventional gas inhalation method. Our results showed that global BOLD signal fluctuation in the frequency range of 0.02-0.04Hz contains the most prominent contribution from natural variation in arterial CO2. The CVR map calculated using this signal as a regressor is reproducible across runs (ICC=0.91±0.06), and manifests a strong spatial correlation with results measured with a conventional hypercapnia-based method in healthy subjects (r=0.88, p<0.001). We also found that resting-state CVR was able to identify vasodilatory deficit in patients with steno-occlusive disease, the spatial pattern of which matches that obtained using the conventional gas method (r=0.71±0.18). These results suggest that CVR obtained with resting-state BOLD may be a useful alternative in detecting vascular deficits in clinical applications when gas challenge is not feasible.
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: peiying.liu@jhu.edu.
authors.forename: Peiying
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Biomedical Engineering Graduate Program, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Pinho
authors.affiliation: Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75235, USA.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Park
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Babu G
authors.initials: BG
authors.lastname: Welch
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Lu
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply* / Q000502:physiology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000503:physiopathology; D012119:Respiration; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
keywords: Cerebrovascular reactivity; Global signal; Hypercapnia (CO(2)) inhalation; Moyamoya disease; Resting-state BOLD fMRI; Spontaneous CO(2) fluctuation