# Quantitative Imaging of Mouse Brain Development

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $593,276

## Abstract

Abstract:
 Brain development is a highly dynamic yet precisely orchestrated process. Using genetically modified mouse
models, we are in the process of unveiling the complex mechanisms that control critical cellular events in the
developing brain. High-throughput imaging tools will greatly benefit studies in this area by charactering brain
phenotypes at the macroscopic/mesoscopic levels and directing subsequent examinations at the cellular and
molecular levels. In this project, multiple novel magnetic resonance imaging (MRI) techniques will be
developed to non-invasively exam a wide range of phenotypes in the developing mouse brain from mid-
embryonic stage to adolescence. The target phenotypes include macroscopic brain morphology and structural
connectivity, microstructural organization, neuronal migration and differentiation, and postnatal brain activity.
The proposed techniques include fast imaging sequences, novel image contrasts, optimized imaging
coils/holder, and image analysis tools, many of which stem from on our existing expertise.
 In Aim 1, we will develop imaging tools to achieve high-throughput in vivo multi-contrast MRI of the
developing mouse brain. We will collect multi-contrast MRI data to construct an in vivo MRI atlas of the
developing mouse brain to assist mouse brain phenotype analysis and
use the sas4-/- mouse, a model of
microcephaly, to test the performance of the technique.
In Aim 2, we will use novel diffusion MRI techniques to
characterize macroscopic morphology, connectivity, and microstructural organization in the developing brain.
In particular, high angular resolution diffusion imaging (HARDI) will be used to resolve complex tissue
microstructural organization and reconstruct connectivity between major brain regions, and the new oscillating
gradient diffusion MRI technique will be used to exam changes in cellularity in the developing cortex
associated with neuronal migration. Detailed examination of the relationships between diffusion MRI-based
markers and specific histological markers will determine their sensitivity to the underlying developmental
processes. In Aim 3, we will use novel Manganese (Mn2+)-enhanced MRI as another tissue contrast, which
reflects postnatal brain activity and potentially neuronal differentiation in the embryonic brain, to examine the
developing mouse brain. We will examine the contrast patterns of Mn2+-enhanced MRI in the embryonic and
neonatal mouse brain with the patterns of neuronal differentiation observed in histological data to determine
the sensitivity of Mn2+-enhanced MRI to neuronal differentiation.
In addition, we will investigate potential toxic
effects of Mn2+ on brain development, and establish protocols that minimize these effects. In Aims 2 and 3, the
techniques will also be used to characterize three mutant mouse models with abnormal brain phenotypes
resulting from defects in neuronal migration and differentiation. The imaging techniques and knowledge gained
in this proje...

## Key facts

- **NIH application ID:** 10362680
- **Project number:** 5R01NS102904-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** JIANGYANG ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $593,276
- **Award type:** 5
- **Project period:** 2018-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10362680

## Citation

> US National Institutes of Health, RePORTER application 10362680, Quantitative Imaging of Mouse Brain Development (5R01NS102904-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10362680. Licensed CC0.

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