# Advancing methods for mapping short-range association fibers in the aging brain

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $133,920

## Abstract

PROJECT ABSTRACT
White matter (WM) microstructural and connectional alterations are increasingly recognized as sensitive
biomarkers of early pathological changes in Alzheimer’s disease (AD). Due to limitations in spatial resolution and
diffusion-encoding sensitivity of conventional diffusion MRI techniques, only long-range fiber tracts in deep WM
have been accurately mapped and studied in AD. Little is known about the short-range association fibers (SAFs)
in superficial WM, even though they contribute to 90% WM connections and are more vulnerable to age-related
degeneration than deep WM according to the retrogenesis model of AD. This proposal aims to improve the
accuracy and feasibility of SAF mapping using ultra-high-resolution (1 mm isotropic or higher) and high-sensitivity
diffusion MRI in AD. Specifically, the candidate will develop an optimal acquisition strategy for in vivo mapping
of SAFs, leveraging knowledge learned from histological validation using ex vivo diffusion MRI and polarization-
sensitive optical coherence tomography; and employ developed methods to quantitatively determine when,
where and how aberrant tissue properties and connections of SAFs occur in AD and how they relate to cognitive
and molecular biomarkers in individuals with concurrent MRI and PET, as well as elucidate the role of short-
range cortico-cortical connections in the spread of pathological tau proteins in AD. This proposal will advance
next-generation diffusion MRI tractography and microstructural imaging at 1 mm isotropic or higher resolution
for mapping SAFs and fine-scale structures across the whole brain in AD, clarify the effectiveness of SAFs as
biomarkers of early pathological changes in AD, and shed light into the spread of tau through axonal connections.
 The candidate’s long-term career goal is to become an independent investigator dedicated to developing
cutting-edge neuroimaging methodology, advancing the clinical utilization of these advanced neuroimaging
technologies in the diagnosis, characterization and tracking of neurodegenerative diseases, and advancing
understanding of the pathological mechanisms that cause dementia. This candidate has in-depth training in
state-of-the-art diffusion MRI and tractography, image processing and analysis, and deep learning. During this
K award, he will work with a multi-disciplinary team of mentors and collaborators to acquire additional expertise
in histological validation, brain aging and neurodegenerative diseases as well as clinical translational research,
which are essential for him to implement the proposed research and lead an independent laboratory. The
exceptional resources, mentorship and collaboration at the Massachusetts General Hospital Martinos Center for
Biomedical Imaging and Alzheimer's Disease Research Center will provide an ideal environment for the
candidate to achieve both his scientific and career development goals.

## Key facts

- **NIH application ID:** 10284540
- **Project number:** 1K99AG073506-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Qiyuan Tian
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $133,920
- **Award type:** 1
- **Project period:** 2021-09-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10284540

## Citation

> US National Institutes of Health, RePORTER application 10284540, Advancing methods for mapping short-range association fibers in the aging brain (1K99AG073506-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10284540. Licensed CC0.

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