Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data
Emma Biondetti,
Antonio Maria Chiarelli,
Michael Germuska,
Ilona Lipp,
Alessandro Villani,
Alessandra S. Caporale,
Eleonora Patitucci,
Kevin Murphy,
Valentina Tomassini,
Richard G. Wise
Affiliations
Emma Biondetti
Department of Neurosciences, Imaging, and Clinical Sciences, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Institute for Advanced Biomedical Technologies, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Corresponding author at: Department of Neurosciences, Imaging, and Clinical Sciences, Institute for Advanced Biomedical Technologies, ‘G. D'Annunzio’ University of Chieti-Pescara, Via dei Vestini 31, Chieti 66100, Italy.
Antonio Maria Chiarelli
Department of Neurosciences, Imaging, and Clinical Sciences, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Institute for Advanced Biomedical Technologies, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy
Michael Germuska
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Physics and Astronomy, Cardiff University, Cardiff, United Kingdom
Ilona Lipp
Department of Neurophysics, Max Planck Institute for Human Cognitive & Brain Sciences, Leipzig, Germany; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK
Alessandro Villani
Department of Neurosciences, Imaging, and Clinical Sciences, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Institute for Advanced Biomedical Technologies, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy
Alessandra S. Caporale
Department of Neurosciences, Imaging, and Clinical Sciences, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Institute for Advanced Biomedical Technologies, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy
Eleonora Patitucci
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK
Kevin Murphy
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Physics and Astronomy, Cardiff University, Cardiff, United Kingdom
Valentina Tomassini
Department of Neurosciences, Imaging, and Clinical Sciences, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK; MS Centre, Neurology Unit, ‘SS. Annunziata’ University Hospital, Chieti, Italy; Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK; Helen Durham Centre for Neuroinflammation, University Hospital of Wales, Cardiff, UK
Richard G. Wise
Department of Neurosciences, Imaging, and Clinical Sciences, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Institute for Advanced Biomedical Technologies, ‘G. D'Annunzio’ University of Chieti-Pescara, Chieti, Italy; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK
BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.
