Quantitative mapping of cerebrovascular reactivity amplitude and delay with breath-hold BOLD fMRI when end-tidal CO2 quality is low

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in response to a vasoactive stimulus, is a clinically useful measure of cerebrovascular health. CVR is often measured using a breath-hold task to modulate blood CO₂levels during an fMRI scan. Measuring end-tidal CO₂(P_ETCO₂) with a nasal cannula during the task allows CVR amplitude to be calculated in standard units (vascular response per unit change in CO₂, or %BOLD/mmHg) and CVR delay to be calculated in seconds. The use of standard units allows for normative CVR ranges to be established and for CVR comparisons to be made across subjects and scan sessions. Although breath holding can be successfully performed by diverse patient populations, obtaining accurate P_ETCO₂measurements requires additional task compliance; specifically, participants must breathe exclusively through their nose and exhale immediately before and after each breath hold. Meeting these requirements is challenging, even in healthy participants, and this has limited the translational potential of breath-hold fMRI for CVR mapping. Previous work has focused on using alternative regressors such as respiration volume per time (RVT), derived from respiration-belt measurements, to map CVR. Because measuring RVT does not require additional task compliance from participants, it is a more feasible measure than P_ETCO₂. However, using RVT does not produce CVR amplitude in standard units. In this work, we explored how to achieve CVR amplitude maps, in standard units, and CVR delay maps, when breath-hold task P_ETCO₂data quality is low. First, we evaluated whether RVT could be scaled to units of mmHg using a subset of P_ETCO₂data of sufficiently high quality. Second, we explored whether a P_ETCO₂timeseries predicted from RVT using deep learning allows for more accurate CVR measurements. Using a dense-mapping breath-hold fMRI dataset, we showed that both rescaled RVT and rescaled, predicted P_ETCO₂can be used to produce maps of CVR amplitude in standard units and CVR delay with strong absolute agreement to ground-truth maps. The rescaled, predicted P_ETCO₂regressor resulted in superior accuracy for both CVR amplitude and delay. In an individual with regions of increased CVR delay due to Moyamoya disease, the predicted P_ETCO₂regressor also provided greater sensitivity to pathology than RVT. Ultimately, this work will increase the clinical applicability of CVR in populations exhibiting decreased task compliance.