# Developmental sensorimotor and cognitive pathways in infant cerebellum with multi-scale imaging

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $252,000

## Abstract

PROJECT SUMMARY
Development of the human cerebellum undergoes a precisely programmed sequence of processes, spanning
from the third trimester of pregnancy into the first postnatal year. Due to advances in neonatal imaging
techniques, cerebellar injury has been increasingly detected in premature infants and full-terms with birth
complications. Although perinatal cerebellar injury and malformation have been broadly associated with
developmental delays in motor, language, cognition, and social behaviors, the underlying biological processes
– causing the functional disorders – have not yet been fully understood. Existing studies have reported conflicting
findings regarding the role regional cerebellum lesions play in motor and socio-cognitive disorders, which are
especially challenging in secondary cerebellar malformation where contralateral cerebral injury is a substantial
confounder. Our exploratory study proposes to address these controversial findings by developing a multi-scale
imaging framework to elucidate the neuroarchitecture and connectivity maps of the first-year cerebellum
development. The framework builds on our preliminary work of 100-500µm-resolution ex vivo magnetic
resonance imaging (MRI) and diffusion MRI as well as 3-10µm-resolution automated serial-sectioning
polarization sensitive optical coherence tomography (as-PSOCT). Essentially, as-PSOCT uses intrinsic optical
properties and adopts a block-face strategy to eliminate tissue distortion in conventional histology and reveal
cellular organizations, myelin content, and orientation of fiber tracts with microscopic precision in volumetric
reconstruction. By co-registering it with the ex vivo MRI on the same sample, cellular level information will be
transferred to the coordinates of the entire brain space. The study design will optimize scan protocols to uncover
sophisticated folding patterns as well as small and less myelinated fiber tracts in the developing cerebellum.
Computational models will be developed to aid cross-modality registration, multi-resolution image fusion and
white matter tractography. The successful completion of this project will, for the first time, generate high-
resolution maps to characterize cerebellar structure and connectivity within the first year of life. The project will
advance our understanding of the role human cerebellum plays in higher cognitive functions. The cerebellar atlas
and connectivity map offer a reference for future clinical evaluations in neurodevelopmental delays in the human
cerebellum. Additionally, the multi-scale technique serves as a more general, intriguing tool for the neuroscience
community to conduct cellular-to-system level investigations in the brain.

## Key facts

- **NIH application ID:** 10461075
- **Project number:** 5R21HD106038-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Hui Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,000
- **Award type:** 5
- **Project period:** 2021-08-03 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461075

## Citation

> US National Institutes of Health, RePORTER application 10461075, Developmental sensorimotor and cognitive pathways in infant cerebellum with multi-scale imaging (5R21HD106038-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10461075. Licensed CC0.

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