title: Validation and optimization of hypercapnic-calibrated fMRI from oxygen-sensitive two-photon microscopy.
abstract: Hypercapnic-calibrated fMRI allows the estimation of the relative changes in the cerebral metabolic rate of oxygen (rCMRO2) from combined BOLD and arterial spin labelling measurements during a functional task, and promises to permit more quantitative analyses of brain activity patterns. The estimation relies on a macroscopic model of the BOLD effect that balances oxygen delivery and consumption to predict haemoglobin oxygenation and the BOLD signal. The accuracy of calibrated fMRI approaches has not been firmly established, which is limiting their broader adoption. We use our recently developed microscopic vascular anatomical network model in mice as a ground truth simulator to test the accuracy of macroscopic, lumped-parameter BOLD models. In particular, we investigate the original Davis model and a more recent heuristic simplification. We find that these macroscopic models are inaccurate using the originally defined parameters, but that the accuracy can be significantly improved by redefining the model parameters to take on new values. In particular, we find that the parameter α that relates cerebral blood-volume changes to cerebral blood-flow changes is significantly smaller than typically assumed and that the optimal value changes with magnetic field strength. The results are encouraging in that they support the use of simple BOLD models to quantify BOLD signals, but further work is needed to understand the physiological interpretation of the redefined model parameters.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.
authors: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Medicine, Laval University, Quebec City, Quebec, Canada Deparment of Electrical Engineering, École Polytechnique Montreal, Montreal, Quebec, Canada lgagnon@nmr.mgh.harvard.edu.
authors: Louis
authors: 0000-0001-7202-5176
authors: L
authors: Gagnon
authors: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors: Sava
authors: S
authors: Sakadžić
authors: Deparment of Electrical Engineering, École Polytechnique Montreal, Montreal, Quebec, Canada.
authors: Frédéric
authors: F
authors: Lesage
authors: Deparment of Electrical Engineering, École Polytechnique Montreal, Montreal, Quebec, Canada.
authors: Philippe
authors: P
authors: Pouliot
authors: Department of Neurosciences and Radiology, UCSD, La Jolla, CA, USA.
authors: Anders M
authors: AM
authors: Dale
authors: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Neurosciences and Radiology, UCSD, La Jolla, CA, USA.
authors: Anna
authors: A
authors: Devor
authors: Department of Radiology, UCSD, La Jolla, CA, USA.
authors: Richard B
authors: RB
authors: Buxton
authors: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors: David A
authors: DA
authors: Boas
mesh_terms: D000818:Animals; D001810:Blood Volume; D001931:Brain Mapping / Q000295:instrumentation / Q000379:methods*; D002138:Calibration; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D054022:Cerebrum / Q000098:blood supply*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton / Q000295:instrumentation / Q000379:methods*; D010100:Oxygen / Q000097:blood*
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen
keywords: Monte Carlo simulations; calibrated fMRI; cerebral metabolism; two-photon microscopy