Angularly Resolved Deep Brain Fluorescence Imaging Using a Single Optical Fiber

Israel J De La Rosa,Ramin Pashaie,Patrick K Cullen,Mehdi Azimipour,Fred J Helmstetter

doi:10.1155/2018/8903413

Abstract

In this article, we report the development of a minimally invasive fiber optic based fluorescence probe which can reach deep brain objects and measure the intensity and spatial distribution of fluorescence signals in the tissue. In this design, the brain is scanned by a single penetrating side-firing optical fiber which delivers excitation light pulses to the tissue at different depths and orientations and simultaneously collects samples of fluorescence emission signals. Signal-to-noise ratio of the measurements is improved by adapting the pulse compression technique and the theory of optimal filters. Effects of each design parameter on the overall performance of the scanner, including the spatial resolution and speed of scanning, are analyzed and experimentally measured. In vivo experiments show that the new device, despite the simplicity of the design, provides valuable information particularly useful in optogenetic stimulation experiments where the exact position of the fiber tip and the radiation orientation can change the outcome of a test.

Highlights

Recent advances in the discovery or synthesis of new fluorescent indicators have been followed by the development of sophisticated technologies for in vitro and in vivo fluorescence imaging offering spatial resolution close to the diffraction limit of adapted optical wavelengths [1]
To better understand and analyze the performance of this scanner, we used the stochastic method of Monte Carlo (MC) [15, 16] to simulate light propagation in a scattering and absorbing medium
The measured full-width halfmaximum (FWHM) are within 20% of the simulation results when the scattering coefficient was fixed but the absorption was changing over a reasonable range

Summary

Introduction

Recent advances in the discovery or synthesis of new fluorescent indicators have been followed by the development of sophisticated technologies for in vitro and in vivo fluorescence imaging offering spatial resolution close to the diffraction limit of adapted optical wavelengths [1]. That model light tissue interaction and use this information to translate the measured data to three-dimensional images that reveal the distribution of fluorescent molecules. Such tomography scanners can image slightly deeper areas; resolution is significantly sacrificed and spurious objects appear in generated images caused by the instability of algorithms that solve ill-posed inverse problems. None of these technologies can reliably image deep brain objects, such as the thalamus or hippocampus, which play crucial roles in vital brain functions including the early processing of sensory inputs or memory consolidation. There is high demand for the invention of new instrumentation that can reach deep brain objects to perform fluorescence imaging

Methods

Results

Conclusion