Model-based correction of rapid thermal confounds in fluorescence neuroimaging of targeted perturbation

Abstract

An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses.Aim: Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses.Approach: We use high precision phased-array 3 MHz focused ultrasound delivery integrated with fiberscope-based widefield fluorescence to monitor cortex-wide calcium changes. Our approach for detecting the neural activation first takes advantage of the high inter-hemispheric correlation of resting state Ca 2þ dynamics and then removes the ultrasound-induced thermal effect by subtracting its simulated spatio-temporal signature from the processed profile. Results:The focused 350 μm-sized ultrasound stimulus triggered rapid localized activation events dominated by transient thermal responses produced by ultrasound. By employing bioheat equation to model the ultrasound heat deposition, we can recover putative neural responses to ultrasound. Conclusions:The developed method for canceling transient thermal fluorescence quenching could also find applications with optical stimulation techniques to monitor thermal effects and disentangle them from neural responses. This approach may help deepen our understanding of the mechanisms and macroscopic effects of ultrasound neuromodulation, further paving the way for tailoring the stimulation regimes toward specific applications.

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation

“…However, these effects generally result in rapid fluorescence dips. 37,38 To address the concern that the dip is due to INS-induced thermal effect on the calcium indicator, we tested the GCaMP6s-labeled neurons in dead mice with no calcium changes. As shown in Fig.…”

Special Section Guest Editorial: Frontiers in Neurophotonics

“…In this Special Section, we feature a primary research paper by Davoudi et al that describes a computational model for correction of thermal fluorescence transients induced by ultrasound neuromodulation. 7 In a perspective article by Bouchard et al, the authors discuss the challenges and possible mitigating strategies related to application of machine learning methods to optical datasets with insufficient amount of labeled data for efficient learning. 8 Another perspective is focused on the problem of the association of pre-and postsynaptic proteins in super-resolution microscopy.…”