Validation and optimization of hypercapnic-calibrated fMRI from oxygen-sensitive two-photon microscopy

Abstract

One contribution of 15 to a Theo Murphy meeting issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. LG, 0000-0001-7202-5176Hypercapnic-calibrated fMRI allows the estimation of the relative changes in the cerebral metabolic rate of oxygen (rCMRO 2 ) 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 a 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'.

Dependence of the MR signal on the magnetic susceptibility of blood studied with models based on real microvascular networks

“…In vivo experiments in humans have found that in calibrated BOLD experiments at 1.5 T, 3 T, and 7 T, which is consistent with recent multicompartment vascular modeling studies that suggest at 3 T . These vascular modeling studies estimated β and α indirectly by treating them as free parameters of the Davis model in simulations of the BOLD signals.…”

“…The microvascular networks used here were obtained using in vivo 2‐photon imaging of the cerebral cortex of C57BL/6 mice and published in previous studies . We used 6 unique microvascular networks obtained from 6 different mice.…”

“…The vascular anatomical network (VAN) model was then applied to these vascular networks. The VAN model is a bottom‐up model that computes blood flow and oxygenation distributions within microscopic vasculature and the resulting MR signal . The steady‐state oxygen distribution is obtained by solving the advection‐diffusion equation until it reaches equilibrium .…”

The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements

“…The first study of this kind is that by Gagnon et al [164]. Gagnon et al used the VAN model, based on the fundamental physiological processes with a microscopic level of detail, to simulate BOLD and ASL signals bottom-up.…”

Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

“…Parcellating cortex in this manner will allow for neuroanatomically valid spatial smoothing of fMRI data and increased statistical power. If these analyses could be combined with information about regional differences in neurovascular coupling and expected BOLD magnitudes [93,94], the power of these new methods could be increased even further, allowing for increased accuracy and validity in understanding functional specialization across the brain.…”