Modeling the carbon-dioxide response function in fMRI under task and resting-state conditions

Conventionally, cerebrovascular reactivity (CVR) is estimated as the amplitude of the hemodynamic response to vascular stimuli. While the CVR amplitude has established clinical utility, the temporal characteristics of CVR have been increasingly explored and may yield even more pathology-sensitive parameters. This work is motivated by the current need to evaluate the feasibility of dCVR modeling in various noise conditions. In this work, we present a comparison of several recently published model-based deconvolution approaches for estimating h(t), including maximum a posterior likelihood (MAP), inverse logit (IL), canonical correlation analysis (CCA), and basis expansion (using Gamma and Laguerre basis sets). To aid the comparison, we devised a novel simulation framework that allowed us to target a wide range of SNRs, ranging from 10 to -7 dB, representative of both task and resting-state CO2 changes. In addition, we built ground-truth h(t) into our simulation framework, overcoming the practical limitation that the true h(t) is unknown in methodological evaluations. Moreover, to best represent realistic noise found in fMRI scans, we extracted it from in-vivo resting-state scans. Furthermore, we introduce a simple optimization of the CCA method (CCAopt) and compare its performance to these existing methods. Our findings suggest that model-based methods can reasonably estimate dCVR even amidst high noise, and in a manner that is largely independent of the underlying model assumptions for each method. We also provide a quantitative basis for making methodological choices, based on the desired dCVR parameters, the estimation accuracy and computation time. The BEL method provided the highest accuracy and robustness, followed by the CCAopt and IL methods. Of the three, the CCAopt method required the lowest computational time. These findings lay the foundation for wider adoption of dCVR estimation in CVR mapping.