Altered Iron and Microstructure in Huntington's Disease Subcortical Nuclei : Insight From 7T MRI

© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine..

BACKGROUND: Pathophysiological changes of Huntington's disease (HD) can precede symptom onset by decades. Robust imaging biomarkers are needed to monitor HD progression, especially before the clinical onset.

PURPOSE: To investigate iron dysregulation and microstructure alterations in subcortical regions as HD imaging biomarkers, and to associate such alterations with motor and cognitive impairments.

STUDY TYPE: Prospective.

POPULATION: Fourteen individuals with premanifest HD (38.0 ± 11.0 years, 9 females; far-from-onset N = 6, near-onset N = 8), 21 manifest HD patients (49.1 ± 12.1 years, 11 females), and 33 age-matched healthy controls (43.9 ± 12.2 years, 17 females).

FIELD STRENGTH/SEQUENCE: 7 T, T1 -weighted imaging, quantitative susceptibility mapping, and diffusion tensor imaging.

ASSESSMENT: Volume, susceptibility, fractional anisotropy (FA), and mean diffusivity (MD) within subcortical brain structures were compared across groups, used to establish HD classification models, and correlated to clinical measures and cognitive assessments.

STATISTICAL TESTS: Generalized linear model, multivariate logistic regression, receiver operating characteristics with the area under the curve (AUC), and likelihood ratio test comparing a volumetric model to one that also includes susceptibility and diffusion metrics, Wilcoxon paired signed-rank test, and Pearson's correlation. A P-value <0.05 after Benjamini-Hochberg correction was considered statistically significant.

RESULTS: Significantly higher striatal susceptibility and FA were found in premanifest and manifest HD preceding atrophy, even in far-from-onset premanifest HD compared to controls (putamen susceptibility: 0.027 ± 0.022 vs. 0.018 ± 0.013 ppm; FA: 0.358 ± 0.048 vs. 0.313 ± 0.039). The model with additional susceptibility, FA, and MD features showed higher AUC compared to volume features alone when differentiating premanifest HD from HC (0.83 vs. 0.66), and manifest from premanifest HD (0.94 vs. 0.83). Higher striatal susceptibility significantly correlated with cognitive deterioration in HD (executive function: r = -0.600; socioemotional function: r = -0.486).

DATA CONCLUSION: 7 T MRI revealed iron dysregulation and microstructure alterations with HD progression, which could precede volume loss, provide added value to HD differentiation, and might be associated with cognitive changes.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Journal of magnetic resonance imaging : JMRI - (2024) vom: 11. Jan.

Sprache:

Englisch

Beteiligte Personen:

Yao, Jingwen [VerfasserIn]
Morrison, Melanie A [VerfasserIn]
Jakary, Angela [VerfasserIn]
Avadiappan, Sivakami [VerfasserIn]
Rowley, Paul [VerfasserIn]
Glueck, Julia [VerfasserIn]
Driscoll, Theresa [VerfasserIn]
Geschwind, Michael D [VerfasserIn]
Nelson, Alexandra B [VerfasserIn]
Possin, Kathrine L [VerfasserIn]
Xu, Duan [VerfasserIn]
Hess, Christopher P [VerfasserIn]
Lupo, Janine M [VerfasserIn]

Links:

Volltext

Themen:

Diffusion tensor imaging
Huntington's disease
Journal Article
Neuroimaging
Quantitative susceptibility mapping
Subcortical nuclei

Anmerkungen:

Date Revised 11.01.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1002/jmri.29195

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366975706