Implications of temporal sampling in voltage imaging microscopy

TL;DR

This paper analyzes how different temporal sampling methods in voltage imaging microscopy affect signal fidelity, providing guidance on optimal sampling parameters and highlighting the performance trade-offs between scanning and wide-field microscopes.

Contribution

It introduces a mathematical framework combining analytical modeling and simulations to compare the effects of temporal sampling in different microscopy modalities.

Findings

Scanning microscopes perform better in low SNR conditions and small spike detection.

Wide-field microscopes excel with high temporal undersampling and large spike detection.

Both modalities converge in performance at high sampling rates.

Abstract

Significance: Voltage imaging microscopy has emerged as a powerful tool to investigate neural activity both in vivo and in vitro. Various imaging approaches have been developed, including point-scanning, line-scanning and wide-field microscopes, however the effects of their different temporal sampling methods on signal fidelity have not yet been fully investigated. Aim: To provide an analysis of the inherent advantages and disadvantages of temporal sampling in scanning and wide-field microscopes and their effect on the fidelity of voltage spike detection. Approach: We develop a mathematical framework based on a mixture of analytical modeling and computer simulations with Monte-Carlo approaches. Results: Scanning microscopes outperform wide-field microscopes in low signal-to-noise conditions and when only a small subset of spikes needs to be detected. Wide-field microscopes outperform scanning microscopes when the measurement is temporally undersampled and a large fraction of the spikes needs to be detected. Both modalities converge in performance as sampling increases and the frame rate reaches the decay rate of the voltage indicator. Conclusions: Our work provides guidance for the selection of optimal temporal sampling parameters for voltage imaging. Most importantly it advises against using scanning voltage imaging microscopes at frame rates below 500 Hz.