# BRAIN CONNECTS: Mapping Connectivity of the Human Brainstem in a Nuclear Coordinate System

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $1,366,957

## Abstract

Project Summary/Abstract (30 lines of text limit)
The ~1 billion neurons that form the human brainstem are organized at multiple scales, ranging from their cell
type-specific patterns of dendritic arborization, to local circuits embedded within large-scale projection systems
spanning the brainstem, and a complex nuclear architecture. In this project, we will image across this vast range
of scales to build technologies to create a multiscale atlas akin to Google Earth for the human brainstem to
visualize brainstem-wide networks and zoom in to the level of individual, labeled cells and their connectivity at
micrometer resolution within the context of individual nuclei. This dramatic advance will be made possible
through the use of an array of imaging technologies, including light-sheet fluorescence microscopy (LSFM),
tissue clearing, immunohisto-chemistry (IHC), 2-photon expansion microscopy (2PEM), magnetic resonance
imaging (MRI) and newly developed techniques in polarization-sensitive optical coherence tomography (PS-
OCT). PS-OCT in particular is a potentially transformative technology as it provides micrometer resolution over
large volumes of tissue, images all of the tissue (as opposed to fluorescence), does not require mounting and
staining, can be automated, is essentially distortion free as it images the tissue prior to cutting, and with
innovations we propose in our project, allows direct measures of 3D axonal orientation. LSM-based IHC will
provide molecular, morphological and spatial properties of cells and their projections that will enable us to nuclear
boundaries to place the connections in a nuclear context, 2PEM will provide direct validation of the 3D-PSOCT,
and the OCT will also enable us to remove the distortions induced by cutting and clearing, and transfer
information to intact brainstem and whole-hemisphere MRI for quantitative atlasing and in vivo inference.

## Key facts

- **NIH application ID:** 10916313
- **Project number:** 5U01NS132181-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Bruce Fischl
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,366,957
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916313

## Citation

> US National Institutes of Health, RePORTER application 10916313, BRAIN CONNECTS: Mapping Connectivity of the Human Brainstem in a Nuclear Coordinate System (5U01NS132181-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10916313. Licensed CC0.

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