Cerebrovascular Reactivity to Hypoxic and Hypercapnic Gas Challenges Using 7T BOLD fMRI

Abstract

BackgroundCerebrovascular reactivity (CVR) is a sensitive marker of vascular health, most commonly measured with BOLD fMRI during hypercapnic gas challenges. Hypoxia is a complementary but under-characterized vasoactive stimulus. We characterize a combined hypercapnic-hypoxic gas-challenge paradigm at 7 Tesla BOLD fMRI and its cross-session reproducibility.

MethodsEleven healthy adults were scanned twice at 7 Tesla during an 18-minute multi-echo, multiband BOLD acquisition, receiving fixed-inspired hypercapnic (5% CO2) and hypoxic (10% O2) gas boluses separated by medical-air recovery periods, with end-tidal gas and peripheral saturation monitoring. Hypercapnic and hypoxic CVR were estimated using three trace-based general linear models -- end-tidal gas, peripheral saturation, and Severinghaus-derived arterial saturation -- and a finite impulse response model. Cross-session reproducibility was assessed by region-of-interest intraclass correlation.

ResultsThe paradigm produced robust, condition-specific gray-matter BOLD responses that reproduced across sessions. The Severinghaus-derived saturation regressor generalized significantly better than end-tidal and peripheral regressors under cross-session validation and outperformed the finite impulse response model in 58% of gray-matter voxels. Reproducibility across cortical, subcortical, and brainstem atlases was moderate-to-high (median cortical intraclass correlation 0.71).

ConclusionA combined hypercapnic-hypoxic paradigm yields reproducible voxelwise cerebrovascular reactivity maps at 7 Tesla; Severinghaus-derived arterial saturation is the most generalizable regressor for hypoxic reactivity.

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Cite

BibTeX RIS

BibTeX

@misc{loparco2026cerebrovascular,
  title = {{Cerebrovascular Reactivity to Hypoxic and Hypercapnic Gas Challenges Using 7T BOLD fMRI}},
  author = {S. LoParco and M. Miedema and G.-Y. Choi and M. Sayeh and J. Wang and M. H. Boudrias and G. Mitsis and R. Hoge},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.11.26362747},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.11.26362747v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Cerebrovascular Reactivity to Hypoxic and Hypercapnic Gas Challenges Using 7T BOLD fMRI
AU  - S. LoParco
AU  - M. Miedema
AU  - G.-Y. Choi
AU  - M. Sayeh
AU  - J. Wang
AU  - M. H. Boudrias
AU  - G. Mitsis
AU  - R. Hoge
PY  - 2026
DA  - 2026/09/11
PB  - medRxiv
DO  - 10.64898/2026.09.11.26362747
UR  - https://www.medrxiv.org/content/10.64898/2026.09.11.26362747v1
AB  - BackgroundCerebrovascular reactivity (CVR) is a sensitive marker of vascular health, most commonly measured with BOLD fMRI during hypercapnic gas challenges. Hypoxia is a complementary but under-characterized vasoactive stimulus. We characterize a combined hypercapnic-hypoxic gas-challenge paradigm at 7 Tesla BOLD fMRI and its cross-session reproducibility.  MethodsEleven healthy adults were scanned twice at 7 Tesla during an 18-minute multi-echo, multiband BOLD acquisition, receiving fixed-inspired hypercapnic (5% CO2) and hypoxic (10% O2) gas boluses separated by medical-air recovery periods, with end-tidal gas and peripheral saturation monitoring. Hypercapnic and hypoxic CVR were estimated using three trace-based general linear models -- end-tidal gas, peripheral saturation, and Severinghaus-derived arterial saturation -- and a finite impulse response model. Cross-session reproducibility was assessed by region-of-interest intraclass correlation.  ResultsThe paradigm produced robust, condition-specific gray-matter BOLD responses that reproduced across sessions. The Severinghaus-derived saturation regressor generalized significantly better than end-tidal and peripheral regressors under cross-session validation and outperformed the finite impulse response model in 58% of gray-matter voxels. Reproducibility across cortical, subcortical, and brainstem atlases was moderate-to-high (median cortical intraclass correlation 0.71).  ConclusionA combined hypercapnic-hypoxic paradigm yields reproducible voxelwise cerebrovascular reactivity maps at 7 Tesla; Severinghaus-derived arterial saturation is the most generalizable regressor for hypoxic reactivity.
ER  -

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