Computing hemodynamic response functions from concurrent spectral fiber-photometry and fMRI data

Abstract

Significance: Although emerging evidence suggests that the hemodynamic response function (HRF) can vary by brain region and species, a single, canonical, human-based HRF is widely used in animal studies. Therefore, the development of flexible, accessible, brain-region specific HRF calculation approaches is paramount as hemodynamic animal studies become increasingly popular.Aim: To establish an fMRI-compatible, spectral, fiber-photometry platform for HRF calculation and validation in any rat brain region.Approach: We used our platform to simultaneously measure (a) neuronal activity via genetically encoded calcium indicators (GCaMP6f), (b) local cerebral blood volume (CBV) from intravenous Rhodamine B dye, and (c) whole brain CBV via fMRI with the Feraheme contrast agent. Empirical HRFs were calculated with GCaMP6f and Rhodamine B recordings from rat brain regions during resting-state and task-based paradigms.Results: We calculated empirical HRFs for the rat primary somatosensory, anterior cingulate, prelimbic, retrosplenial, and anterior insular cortical areas. Each HRF was faster and narrower than the canonical HRF and no significant difference was observed between these cortical regions. When used in general linear model analyses of corresponding fMRI data, the empirical HRFs showed better detection performance than the canonical HRF.Conclusions: Our findings demonstrate the viability and utility of fiber-photometry-based HRF calculations. This platform is readily scalable to multiple simultaneous recording sites, and adaptable to study transfer functions between stimulation events, neuronal activity, neurotransmitter release, and hemodynamic responses.

Fiber-based lactate recordings with fluorescence resonance energy transfer sensors by applying an magnetic resonance-informed correction of hemodynamic artifacts

“…The MR-based method presented in this study provides a feasible alternative, for combined fluorescence-MRI measurements. 25 – 32 , 34 It is also readily applicable with separate MRI measurements, as shown here for phCBV. Furthermore, our correction method can be applied to recordings of any fluorescence sensor.…”

“…Although magnetic resonance (MR) compatible microscopes have been developed 21 , 22 and cortex-wide calcium imaging has been successfully performed during fMRI, 23 fiber-based fluorescence recordings 24 have found widespread application for simultaneous fluorescence-fMRI recordings. 25 – 34 …”

Spatiotemporal patterns of spontaneous brain activity: a mini-review

“… 69 Fiber photometry is another promising approach that has been increasingly used for multimodal fMRI studies. 72 – 76 Fiber photometry allows for cell-type-specific fluorescence imaging such as wide-field optical imaging with the placement of one or more fibers that can target specific neural populations or regions of interest.…”

“… 77 Fiber photometry tracts can be multichannel and capture signals from multiple fluorophores or physiological sources at once. 74 Chao et al. 74 recently used a fiber photometry/fMRI approach to simultaneously measure GCaMP6f fluorescence, photometry-based cerebral blood volume (CBV), and fMRI CBV.…”

“… 74 Chao et al. 74 recently used a fiber photometry/fMRI approach to simultaneously measure GCaMP6f fluorescence, photometry-based cerebral blood volume (CBV), and fMRI CBV. This fiber photometry approach allowed them to estimate hemodynamic response functions in different subcortical nuclei, an analysis that could not be made with a superficial approach such as wide-field optical imaging.…”