INS-fOCT: a label-free, all-optical method for simultaneously manipulating and mapping brain function

Abstract

Significance: Current approaches to stimulating and recording from the brain have combined electrical or optogenetic stimulation with recording approaches, such as two-photon, electrophysiology (EP), and optical intrinsic signal imaging (OISI). However, we lack a label-free, all-optical approach with high spatial and temporal resolution. Aim: To develop a label-free, all-optical method that simultaneously manipulates and images brain function using pulsed near-infrared light (INS) and functional optical coherence tomography (fOCT), respectively. Approach: We built a coregistered INS, fOCT, and OISI system. OISI and EP recordings were employed to validate the fOCT signals. Results: The fOCT signal was reliable and regional, and the area of fOCT signal corresponded with the INS-activated region. The fOCT signal was in synchrony with the INS onset time with a delay of ∼30 ms. The magnitude of fOCT signal exhibited a linear correlation with the INS radiant exposure. The significant correlation between the fOCT signal and INS was further supported by OISI and EP recordings. Conclusions: The proposed fiber-based, all-optical INS-fOCT method allows simultaneous stimulation and mapping without the risk of interchannel cross-talk and the requirement of contrast injection and viral transfection and offers a deep penetration depth and high resolution.

Targeted Optical Neural Stimulation: A New Era for Personalized Medicine

“…Clinicians may begin to evaluate disease in a network-based way, rather than a location-based way. Although many steps remain between research in INS and implementation of diagnosis and treatment, we suggest a possible circuit-based framework for achieving precision medicine, and suggest a promising bridge between optical neural stimulation and clinical application (Cayce and others 2011; Mou and others 2015; Shi and others 2021; Xu and others 2019; Zhang and others 2020).…”

“…We hypothesized that stimulating at the cortical surface is likely to activate not only cells in superficial layers (leading to activation of cortico-cortical connections) but also the apical dendrites of deep layer neurons (leading to activation of subcortical sites). As a first study of the effects across cortical laminae, a recent study (Zhang and others 2020) introduced a combination of functional optical coherence tomography (fOCT) with INS for brain mapping. fOCT records cortical responses within a laminar depth of 1.0 mm under the cortical surface, illustrating the laminar depth effects of INS.…”

Optical coherence tomography imaging of evoked neural activity in sciatic nerve of rat

“…While fast changes caused by electrical activity occur in the order of milliseconds, and have been imaged in abdominal ganglion of sea slug and in unmyelinated axons of squid and crayfish using intensity [11,14], birefringence [25], and phase [13][14][15] based OCT techniques applied to images with one spatial (depth) and one temporal dimension, called an M-scan, or in one study [25] with temporally spaced Bscans. Researchers have also measured both the hemodynamic and electrophysiological changes in mammalian cortical tissue using intensity-based OCT techniques by employing prolonged stimulus durations [26][27][28] and during artificially induced epileptiform activity [29]. While the results of these studies [11,[13][14][15][22][23][24][25][26][27][28][29] demonstrate great promise for OCT in functional imaging of neural activity, in several studies [11,[13][14][15]25] the tissues were non-mammalian and so are not easily translatable to clinical applications for humans, and in all studies the tissues were unmyelinated and so differ in cytostructure from myelinated fibres, figures 1(a) and (b).…”

“…Researchers have also measured both the hemodynamic and electrophysiological changes in mammalian cortical tissue using intensity-based OCT techniques by employing prolonged stimulus durations [26][27][28] and during artificially induced epileptiform activity [29]. While the results of these studies [11,[13][14][15][22][23][24][25][26][27][28][29] demonstrate great promise for OCT in functional imaging of neural activity, in several studies [11,[13][14][15]25] the tissues were non-mammalian and so are not easily translatable to clinical applications for humans, and in all studies the tissues were unmyelinated and so differ in cytostructure from myelinated fibres, figures 1(a) and (b). Expanding functional imaging with OCT from unmyelinated fibres and neurons to myelinated fibres is important because the latter have distinct roles in communication within the central and peripheral nervous systems, and unique pathologies, such as multiple sclerosis [30].…”

Ultra-parallel label-free optophysiology of neural activity

“…Therefore, label-free optical microscopy has the versatility to image the functional states of neurons and the neuronal microenvironment at the necessary spatiotemporal scales. A prevalent technique for label-free imaging of neuronal activity involves optical coherence tomography (OCT) and optical coherence microscopy (OCM) for neural imaging ( Akkin et al., 2007 , 2009 , 2010 ; Baran and Wang, 2016 ; Chen et al., 2009 ; Graf et al., 2009 ; Lazebnik et al., 2003 ; Li et al., 2020 ; Son et al., 2016 ; Strangman et al., 2002 ; Yeh et al., 2015 ; Zhang et al., 2020 ). As a natural extension of hemodynamic optical imaging in neuroscience ( Li et al., 2020 ; Strangman et al., 2002 ), functional OCT and OCT angiography have been used to infer the neural activity indirectly ( Baran and Wang, 2016 ; Son et al., 2016 ).…”