Functional imaging through scattering medium via fluorescence speckle demixing and localization

TL;DR

This paper introduces a novel method for non-invasive deep tissue imaging by analyzing fluorescent speckle patterns with matrix factorization to localize individual emitters behind scattering media.

Contribution

It demonstrates that fluorescent speckle patterns, previously considered uninformative, can be used for precise emitter localization in scattering tissues, enabling functional imaging at depth.

Findings

Successfully localized fluorescent emitters behind scattering phantoms.

Imaged neural activity through a 200 micron brain slice.

Validated approach with large groups of fluorescent sources.

Abstract

Recently, fluorescence-based optical techniques have emerged as a powerful tool to probe information in the mammalian brain. However, tissue heterogeneities prevent clear imaging of deep neuron bodies due to light scattering. While several up-to-date approaches based on ballistic light allow to retrieve information at shallow depths inside the brain, non-invasive localization and functional imaging at depth still remains a challenge. It was recently shown that functional signals from time-varying fluorescent emitters located behind scattering samples could be retrieved by using a matrix factorization algorithm. Here we show that the seemingly information-less, low-contrast fluorescent speckle patterns recovered by the algorithm can be used to locate each individual emitter, even in the presence of background fluorescence. We test our approach by imaging the temporal activity of large groups of fluorescent sources behind different scattering phantoms mimicking biological tissues, and through a brain slice with a thickness of ~200 micron.