title: Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe.
abstract: The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, lgagnon@nmr.mgh.harvard.edu.
authors.forename: Louis
authors.initials: L
authors.lastname: Gagnon
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Sava
authors.initials: S
authors.lastname: Sakadžić
authors.affiliation: Department of Electrical Engineering, École Polytechnique de Montréal, Montréal, Quebec, Canada H3C 3A7, and.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lesage
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Musacchia
authors.affiliation: Department of Electrical Engineering, École Polytechnique de Montréal, Montréal, Quebec, Canada H3C 3A7, and.
authors.forename: Joël
authors.identifier: http://orcid.org/0000-0002-6652-2130
authors.initials: J
authors.lastname: Lefebvre
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Meryem A
authors.initials: MA
authors.lastname: Yücel
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Karleyton C
authors.initials: KC
authors.lastname: Evans
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Emiri T
authors.initials: ET
authors.lastname: Mandeville
authors.affiliation: Department of Electrical Engineering, École Polytechnique de Montréal, Montréal, Quebec, Canada H3C 3A7, and.
authors.forename: Jülien
authors.initials: J
authors.lastname: Cohen-Adad
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Polimeni
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Yaseen
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Radiology, UC San Diego, La Jolla, California 92093.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Buxton
authors.affiliation: Departments of Neurosciences and Radiology, UC San Diego, La Jolla, California 92093.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, Departments of Neurosciences and Radiology, UC San Diego, La Jolla, California 92093.
authors.forename: Anna
authors.initials: A
authors.lastname: Devor
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139.
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000502:physiology; D005456:Fluorescent Dyes; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D008955:Models, Cardiovascular; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005456:Fluorescent Dyes
keywords: BOLD-fMRI; Monte Carlo; modeling; two-photon microscopy