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

• Published in: PloS one Vol. 14; no. 5; p. e0215294
• Main Authors: van Niftrik, Christiaan Hendrik Bas, Piccirelli, Marco, Muscas, Giovanni, Sebök, Martina, Fisher, Joseph Arnold, Bozinov, Oliver, Stippich, Christoph, Valavanis, Antonios, Regli, Luca, Fierstra, Jorn
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.05.2019; Public Library of Science (PLoS)
• Subjects: Adult; Algorithms; Biology and Life Sciences; Brain; Brain - blood supply; Brain - diagnostic imaging; Brain cancer; Brain mapping; Carbon dioxide; Cerebellum; Cerebrovascular Circulation; Cerebrovascular disorders; Computer and Information Sciences; Correlation; Correlation coefficient; Correlation coefficients; Data interpretation; Earth Sciences; Ecology and Environmental Sciences; Engineering and Technology; Female; Functional magnetic resonance imaging; Humans; Hypercapnia; Hypercapnia - diagnostic imaging; Image Processing, Computer-Assisted; Impact analysis; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medicine and Health Sciences; Motor task performance; Neuroimaging; Neurosciences; Neurosurgery; Neurovascular Coupling; NMR; Nuclear magnetic resonance; Operculum; Oxygenation; Physical Sciences; Postcentral gyrus; Precentral gyrus; Quantitative analysis; Research and Analysis Methods; Supplementary motor area; Switzerland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0215294

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.