Higher spatial resolution diffusion-weighted imaging improves characterization of white matter disconnection in Alzheimer’s disease

Sep 30, 2026

Uploaded by Noah

Alzheimer’s disease is marked by neuropathology accumulation alongside degradation of white matter (WM) structural pathways that connect distributed brain regions. Prior diffusion-weighted imaging (DWI) studies often use standard spatial resolution, which limits resolution of fine-grained WM connections involving crossing fibers or high curvature. This study compares high-resolution multishot multiplexed sensitivity encoding (MUSE) DWI with standard-resolution DWI in demographically matched participants with AD and healthy controls. Graph-theoretical network results show greater AD-related reductions between-network connectivity and increased system segregation for both protocols, while high-resolution MUSE provides higher sensitivity and specificity to AD differences, supporting detection of subtle WM connectivity changes with a clinically feasible method.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Introduction

Research Article | Higher spatial resolution diffusion-weighted imaging improves characterization of white matter disconnection in Alzheimer’s disease
Jenna L. Merensteina,b, Allen W. Songb, Kim G. Johnsonc, Heather E. Whitsond,e, David J. Maddenb,c
aDepartment of Psychology, University of Utah, Salt Lake City, UT, United States
bBrain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, United States
cDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States dCenter for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, United States
eDurham VA Geriatrics Research Education and Clinical Center, Durham, NC, United States Corresponding Author: Jenna L. Merenstein ([jenna.merenstein@utah.edu](jenna.merenstein@utah.edu)) | | --- | | ABSTRACT
In addition to the accumulation of neuropathologies (i.e. , amyloid beta, neurofibrillary tangles), Alzheimer’s disease (AD) is associated with the degradation of white matter (WM) structural pathways that connect distributed brain regions. However, previous studies of AD-related decreases in WM structural connectivity have primarily used standard spatial resolution diffusion-weighted imaging (DWI) acquisitions, which cannot adequately resolve WM connections in fine-grained regions with crossing fibers or high curvature. To better assess more subtle WM tissue degradation in AD, this DWI study compared measures of structural connectivity derived from a high-resolution multishot multiplexed sensitivity encoding (MUSE) acquisition (1 mm isotropic voxels; 1 µl volume) and a standard resolution acquisition (1 .5 mm isotropic voxels; 3.375 µl volume), using a sample of 24 participants with AD and 24 demographically matched healthy controls. Graph theoretical measures of within-network connectivity, betweennetwork connectivity, and system segregation were obtained from a standard network partition. As expected, results indicated larger AD-related decreases in between-network than within-network connectivity, leading to increased network segregation for both DWI acquisitions. However, the high-resolution MUSE DWI acquisition achieved higher sensitivity and specificity to AD-related differences in structural connectivity than the standard resolution DWI protocol, consistent with prior findings from rodents and healthy adults across the lifespan. Together, these findings suggest that this clinically feasible, high-resolution MUSE DWI methodology may detect more subtle AD-related differences in WM connectivity than standard resolution DWI acquisitions.
Keywords: magnetic resonance imaging, graph theoretical analyses, structural connectivity, system segregation, multiplexed sensitivity encoding, neurodegeneration | 1. INTRODUCTION Decline in the microstructural composition of white matter (WM) over the course of adulthood contributes to a disconnection of distributed brain regions, and ultimately toa decline in cognition, even in healthy adults (Bennett & Madden, 2014; Salat, 2011) . This decline in WM connectivity is magnified in adults with Alzheimer’s disease (AD; Chen et al. , 2023; Gold et al. , 2012; Mayo et al. , 2017), and can be assessed in vivo using a noninvasive MRI technique termed diffusion-weighted imaging (DWI) . Studies capitalizing on standard DWI acquisitions have been fundamental for furthering our understanding of WM disconnection in numerous diseases and conditions, such as traumatic brain injury, multiple sclerosis, and anxiety Revision: 17 October 2025 Accepted: 26 November 2025 Available Online: 8 December 2025 © 2025 The Authors. Published under a Creative Commons Attribution 4.0 International (CC BY 4 .0) license. Imaging Neuroscience, Volume 4, 2026 [https://doi.org/10.1162/IMAG.a.1078](https://doi.org/10.1162/IMAG.a.1078) (Armstrong et al. , 2024; Glenn et al. , 2022; Lakhani et al. , 2020) . However, the relatively low spatial resolut

FAQs

How does this study compare imaging protocols for assessing WM connectivity in Alzheimer’s disease?

It compares structural connectivity measures derived from a high-resolution multishot multiplexed sensitivity encoding (MUSE) DWI acquisition versus a standard-resolution DWI acquisition, using matched participants with AD and healthy controls.

Which network-level findings differed between Alzheimer’s disease and controls?

Results indicate larger AD-related decreases in between-network connectivity than within-network connectivity, accompanied by increased network segregation for both DWI acquisitions.

Why is high-resolution MUSE DWI expected to detect more subtle differences?

Standard DWI resolution cannot adequately resolve WM connections in regions with crossing fibers or high curvature; the high-resolution MUSE approach achieved higher sensitivity and specificity to AD-related structural connectivity differences.

Sep 30, 2026

Uploaded by Noah