# CONNECTOME 2.0: DEVELOPING THE NEXT GENERATION HUMAN MRI SCANNER FOR BRIDGING STUDIES OF THE MICRO-, MESO- AND MACRO-CONNECTOME

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $420,000

## Abstract

SUMMARY
The pathological changes of Alzheimer’s disease (AD) develop long before the onset of symptoms, with the
gradual accumulation of molecular pathology in the cerebral cortex followed by neuronal damage. While
macroscopic brain changes such as hippocampal atrophy and cortical thickness are well-established as markers
of symptomatic AD, the predictive value of such macroscopic imaging measures is limited prior to the onset of
dementia. Diffusion MRI has emerged as a sensitive tool for probing microstructural alterations throughout the
whole brain not visible on conventional MRI. The multi-scale advanced diffusion microstructural measures that
are being developed for the Connectome 2.0 project for mapping differences in cortical laminar structure
throughout the whole brain are timely, relevant and hold great promise for capturing the earliest microscopic gray
matter abnormalities present in AD, before their overt manifestation on conventional MRI. The goal of the
proposed supplement is to leverage the unique capabilities of Connectome 2.0, the next-generation human MRI
scanner for imaging structural anatomy and connectivity spanning the microscopic, mesoscopic and
macroscopic scales, to map alterations in neuronal microstructure and connectivity in patients with mild cognitive
impairment (MCI) and AD, as well as individuals at risk of developing AD. This work will build on the hardware
and acquisition advances of the Connectome 2.0 study to push the limits of diffusion MRI sensitivity for mapping
gray matter microstructure and provide validated measures of cortical degeneration in MCI/AD patients and
individuals at risk of developing AD. We propose to acquire advanced diffusion MRI measures on the
Connectome scanner to map cortical and white matter microstructure in MCI/AD patients from the
Massachusetts General Hospital Alzheimer’s Disease Research Center (MADRC) and individuals from the
Human Connectome Project-Lifespan/Aging (HCP-Aging) cohort at biomarker or genetic risk for developing AD,
including evidence of abnormal protein deposition on amyloid and tau PET imaging and/or presence of known
genetic risk factors. Aim 1 will apply advanced diffusion MRI acquisition techniques developed for Connectome
2.0 to infer neuronal and axonal microstructure in MCI and AD patients and older adults with biomarker risk for
developing AD. Aim 2 will validate diffusion MRI measures of cellular and axonal morphology in vulnerable
regions of the brain in postmortem brain specimens obtained from patients with pathology-proven AD. At the end
of this supplement, we anticipate the development of a validated, multi-scale advanced diffusion MRI protocol
targeted for evaluating alterations in cortical and white matter microstructure and macroscopic connectivity in
older adults with differing AD pathology status, with clear measures that can be eventually translated and
disseminated to large-scale AD studies. Such information will inform the interpretation of dif...

## Key facts

- **NIH application ID:** 10123609
- **Project number:** 3U01EB026996-03S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** PETER J. BASSER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,000
- **Award type:** 3
- **Project period:** 2018-09-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123609

## Citation

> US National Institutes of Health, RePORTER application 10123609, CONNECTOME 2.0: DEVELOPING THE NEXT GENERATION HUMAN MRI SCANNER FOR BRIDGING STUDIES OF THE MICRO-, MESO- AND MACRO-CONNECTOME (3U01EB026996-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123609. Licensed CC0.

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