# A Scalable Platform for Exploring and Analyzing Whole Brain Tissue Cleared Images

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $335,104

## Abstract

Abstract
 The ability of accurate localize and characterize cells in light sheet fluorescence microscopy (LSFM) image is
indispensable for shedding new light on the understanding of three dimensional structures of the whole brain. In
our previous work, we have successfully developed a 2D nuclear segmentation method for the nuclear cleared
microscopy images using deep learning techniques. Although the convolutional neural networks show promise
in segmenting cells in LSFM images, our previous work is confined in 2D segmentation scenario and suffers
from the limited number of annotated data. In this project, we aim to develop a high throughput 3D cell
segmentation engine, with the focus on improving the segmentation accuracy and generality. First, we will
develop a cloud based semi-automatic annotation platform using the strength of virtual reality (VR) and crowd
sourcing. The user-friendly annotation environment and stereoscopic view in VR can significantly improve the
efficiency of manual annotation. We design a semi-automatic annotation workflow to largely reduce human
intervention, and thus improve both the accuracy and the replicability of annotation across different users.
Enlightened by the spirit of citizen science, we will extend the annotation software into a crowd sourcing platform
which allows us to obtain a massive number of manual annotations in short time. Second, we will develop a fully
3D cell segmentation engine using 3D convolutional neural networks trained with the 3D annotated samples.
Since it is often difficult to acquire isotropic LSFM images, we will further develop a super resolution method to
impute a high resolution image to facilitate the 3D cell segmentation. Third, we will develop a transfer learning
framework to make our 3D cell segmentation engine general enough to the application of novel LSFM data which
might have significant gap of image appearance due to different imaging setup or clearing/staining protocol. This
general framework will allow us to rapidly develop a specific cell segmentation solution for new LSFM data with
very few or even no manual annotations, by transferring the existing 3D segmentation engine that has been
trained with a sufficient number of annotated samples. Fourth, we will apply our computational tools to several
pilot neuroscience studies: (1) Investigating how topoisomerase I (one of the autism linked transcriptional
regulators) regulates brain structure, and (2) Investigating genetic influence on cell types in the developing
human brain by quantifying the number of progenitor cells in fetal cortical tissue. Successful carrying out our
project will have wide-reaching impact in neuroscience community in visualizing and analyzing complete cellular
resolution maps of individual cell types within healthy and disease brain. The improved cell segmentation engine
in 3D allows scientists from all over the world to share and process each other’s data accurately and efficiently,
thus increasing re...

## Key facts

- **NIH application ID:** 10244882
- **Project number:** 5R01NS110791-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Guorong Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,104
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244882

## Citation

> US National Institutes of Health, RePORTER application 10244882, A Scalable Platform for Exploring and Analyzing Whole Brain Tissue Cleared Images (5R01NS110791-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10244882. Licensed CC0.

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