Examining temporal features of BOLD-based cerebrovascular reactivity in clinical populations

Kayley-Jasmin Marchena-Romero; Xiang Ji; Rosa Sommer; Andrew Centen; Joel Ramirez; Joshua M Poulin; David Mikulis; Michael Thrippleton; Joanna Wardlaw; Andrew Lim; Sandra E Black; Bradley J MacIntosh

doi:10.3389/fneur.2023.1199805

Examining temporal features of BOLD-based cerebrovascular reactivity in clinical populations

Front Neurol. 2023 Jun 15:14:1199805. doi: 10.3389/fneur.2023.1199805. eCollection 2023.

Authors

Kayley-Jasmin Marchena-Romero^{1

2}, Xiang Ji^{2

3}, Rosa Sommer^{2

3

4}, Andrew Centen², Joel Ramirez^{2

3}, Joshua M Poulin^{2

3}, David Mikulis^{4

5

6}, Michael Thrippleton⁷, Joanna Wardlaw⁷, Andrew Lim^{2

4}, Sandra E Black^{2

3}, Bradley J MacIntosh^{1

2

3}

Affiliations

¹ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
² Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
³ Dr. Sandra Black Centre for Brain Resilience and Recovery, Toronto, ON, Canada.
⁴ Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
⁵ Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
⁶ Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
⁷ Brain Research Imaging Centre, Centre for Clinical Brain Sciences, UK Dementia Research Institute Centre, The University of Edinburgh, Edinburgh, United Kingdom.

Abstract

Background: Conventional cerebrovascular reactivity (CVR) estimation has demonstrated that many brain diseases and/or conditions are associated with altered CVR. Despite the clinical potential of CVR, characterization of temporal features of a CVR challenge remains uncommon. This work is motivated by the need to develop CVR parameters that characterize individual temporal features of a CVR challenge.

Methods: Data were collected from 54 adults and recruited based on these criteria: (1) Alzheimer's disease diagnosis or subcortical Vascular Cognitive Impairment, (2) sleep apnea, and (3) subjective cognitive impairment concerns. We investigated signal changes in blood oxygenation level dependent (BOLD) contrast images with respect to hypercapnic and normocapnic CVR transition periods during a gas manipulation paradigm. We developed a model-free, non-parametric CVR metric after considering a range of responses through simulations to characterize BOLD signal changes that occur when transitioning from normocapnia to hypercapnia. The non-parametric CVR measure was used to examine regional differences across the insula, hippocampus, thalamus, and centrum semiovale. We also examined the BOLD signal transition from hypercapnia back to normocapnia.

Results: We found a linear association between isolated temporal features of successive CO₂ challenges. Our study concluded that the transition rate from hypercapnia to normocapnia was significantly associated with the second CVR response across all regions of interest (p < 0.001), and this association was highest in the hippocampus (R² = 0.57, p < 0.0125).

Conclusion: This study demonstrates that it is feasible to examine individual responses associated with normocapnic and hypercapnic transition periods of a BOLD-based CVR experiment. Studying these features can provide insight on between-subject differences in CVR.

Keywords: blood oxygenation level dependent functional magnetic resonance imaging; cerebrovascular reactivity; inter-regional heterogeneity; non-parametric; sleep apnea; small vessel disease.