The voxel-wise analysis of false negative fMRI activation in regions of provoked impaired cerebrovascular reactivity

Christiaan Hendrik Bas van Niftrik; Marco Piccirelli; Giovanni Muscas; Martina Sebök; Joseph Arnold Fisher; Oliver Bozinov; Christoph Stippich; Antonios Valavanis; Luca Regli; Jorn Fierstra

doi:10.1371/journal.pone.0215294

The voxel-wise analysis of false negative fMRI activation in regions of provoked impaired cerebrovascular reactivity

PLoS One. 2019 May 6;14(5):e0215294. doi: 10.1371/journal.pone.0215294. eCollection 2019.

Authors

Christiaan Hendrik Bas van Niftrik^{1

2}, Marco Piccirelli^{2

3}, Giovanni Muscas^{1

2

4}, Martina Sebök^{1

2}, Joseph Arnold Fisher⁵, Oliver Bozinov^{1

2}, Christoph Stippich^{2

3}, Antonios Valavanis^{2

3}, Luca Regli^{1

2}, Jorn Fierstra^{1

2}

Affiliations

¹ Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³ Department of Neuroradiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ Department of Neurosurgery, Careggi University Hospital, Florence, University of Florence, Florence, Italy.
⁵ Department of Anesthesiology, University Health Network, University of Toronto, Toronto, ON, Canada.

Abstract

Task-evoked Blood-oxygenation-level-dependent (BOLD-fMRI) signal activation is widely used to interrogate eloquence of brain areas. However, data interpretation can be improved, especially in regions with absent BOLD-fMRI signal activation. Absent BOLD-fMRI signal activation may actually represent false-negative activation due to impaired cerebrovascular reactivity (BOLD-CVR) of the vascular bed. The relationship between impaired BOLD-CVR and BOLD-fMRI signal activation may be better studied in healthy subjects where neurovascular coupling is known to be intact. Using a model-based prospective end-tidal carbon dioxide (CO2) targeting algorithm, we performed two controlled 3 tesla BOLD-CVR studies on 17 healthy subjects: 1: at the subjects' individual resting end-tidal CO2 baseline. 2: Around +6.0 mmHg CO2 above the subjects' individual resting baseline. Two BOLD-fMRI finger-tapping experiments were performed at similar normo- and hypercapnic levels. Relative BOLD fMRI signal activation and t-values were calculated for BOLD-CVR and BOLD-fMRI data. For each component of the cerebral motor-network (precentral gyrus, postcentral gyrus, supplementary motor area, cerebellum und fronto-operculum), the correlation between BOLD-CVR and BOLD-fMRI signal changes and t-values was investigated. Finally, a voxel-wise quantitative analysis of the impact of BOLD-CVR on BOLD-fMRI was performed. For the motor-network, the linear correlation coefficient between BOLD-CVR and BOLD-fMRI t-values were significant (p<0.01) and in the range 0.33-0.55, similar to the correlations between the CVR and fMRI Δ%signal (p<0.05; range 0.34-0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Δ%signal and t-value change between normo- and hypercapnia. Our main finding is that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-CVR and highlights the importance of a complementary BOLD-CVR assessment in addition to a task-evoked BOLD fMRI to identify brain areas at risk for false-negative BOLD-fMRI signal activation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Algorithms
Brain / blood supply*
Brain / diagnostic imaging
Cerebrovascular Circulation
Female
Humans
Hypercapnia / diagnostic imaging*
Image Processing, Computer-Assisted
Magnetic Resonance Imaging / methods*
Male
Neurovascular Coupling

Grants and funding

Christiaan Hendrik Bas van Niftrik and Jorn Fierstra are supported by the Swiss Cancer League (KFS-3975-08-2016-R) and by Forschungskredit; Postdoc. Zurich University FK-16-040. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.