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Adaptive optics two-photon endomicroscopy enables deep-brain imaging at synaptic resolution over large volumes

ABSTRACT: An innovative imaging tool enables in vivo high-resolution visualization of deep brain structures and functions over large volume. Optical deep-brain imaging in vivo at high resolution has remained a great challenge over the decades. Two-photon endomicroscopy provides a minimally invasive approach to image buried brain structures, once it is integrated with a gradient refractive index (GRIN) lens embedded in the brain. However, its imaging resolution and field of view are compromised by the intrinsic aberrations of the GRIN lens. Here, we develop a two-photon endomicroscopy by adding adaptive optics based on direct wavefront sensing, which enables recovery of diffraction-limited resolution in deep-brain imaging. A new precompensation strategy plays a critical role to correct aberrations over large volumes and achieve rapid random-access multiplane imaging. We investigate the neuronal plasticity in the hippocampus, a critical deep brain structure, and reveal the relationship between the somatic and dendritic activity of pyramidal neurons.

SUBMITTER: Qin Z

PROVIDER: S-EPMC7527232 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Project description:Importance:Targeting the early pathogenic steps in Stargardt disease type 1 (STGD1) is critical to advance our understanding of this condition and to develop potential therapies. Lipofuscin precursors may accumulate within photoreceptors, leading to photoreceptor damage and preceding retinal pigment epithelial (RPE) cell death. Fluorescence adaptive optics scanning light ophthalmoscopy can provide autofluorescence (AF) images in vivo with microscopic resolution to elucidate the cellular origin of AF abnormalities in STGD1. Objective:To study the spatial distribution of photoreceptor, RPE, and AF abnormalities in patients with STGD1 at a cellular level. Design, Setting, and Participants:Cross-sectional study using fluorescence adaptive optics scanning light ophthalmoscopy to compare the cones, rods, and RPE cells between 3 patients with STGD1 and 1 control individual. Imaging sessions were conducted at the University of Rochester. Further image analyses were performed at Beijing Tongren Eye Center and the University of Pittsburgh. Data were collected from August 2015 to February 2016, and analysis began in March 2016. Main Outcomes and Measures:Structural appearance of cones, rods, and AF structures at different retinal locations. Results:Two women and 1 man with macular atrophy phenotype of STGD1 and visual acuity loss ranging from 20/30 to 20/150 and 1 woman without STGD1 with 20/20 visual acuity were analyzed. Cone and rod spacing was increased in all 3 patients at all locations where photoreceptors were detectable; most cones had a dark appearance. Autofluorescence was low contrast but contained structures consistent with RPE cells in the periphery. In the transition zone peripheral to the foveal atrophic lesion, the structural pattern of AF was more consistent with photoreceptors than RPE cells. The microscopic AF was disrupted within areas of clinically detectable atrophy. Conclusions and Relevance:Adaptive optics high-resolution images of cones, rods, and RPE cells at the leading disease front of STGD1 macular atrophy show an AF pattern that appears to colocalize with photoreceptors or may result from a combination of AF signals from both RPE cells and photoreceptors. This in vivo observation is consistent with histologic reports of fluorescence arising from photoreceptors in STGD1. The detection of bisretinoid accumulation in the photoreceptors may represent an early pathologic step in STGD1 and can provide an in vivo imaging tool to act as a biomarker of disease progression.

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Adaptive optics two-photon endomicroscopy enables deep-brain imaging at synaptic resolution over large volumes

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