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T1? imaging in premanifest Huntington disease reveals changes associated with disease progression.

ABSTRACT: Imaging biomarkers sensitive to Huntington's disease (HD) during the premanifest phase preceding motor diagnosis may accelerate identification and evaluation of potential therapies. For this purpose, quantitative MRI sensitive to tissue microstructure and metabolism may hold great potential. We investigated the potential value of T1? relaxation to detect pathological changes in premanifest HD (preHD) relative to other quantitative relaxation parameters.Quantitative MR parametric mapping was used to assess differences between 50 preHD subjects and 26 age- and sex-matched controls. Subjects with preHD were classified into two progression groups based on their CAG-age product (CAP) score; a high and a low/moderate CAP group. Voxel-wise and region-of-interest analyses were used to assess changes in the quantitative relaxation times.T1? showed a significant increase in the relaxation times in the high-CAP group, as compared to controls, largely in the striatum. The T1? changes in the preHD subjects showed a significant relationship with CAP score. No significant changes in T2 or T2* relaxation times were found in the striatum. T2* relaxation changes were found in the globus pallidus, but no significant changes with disease progression were found.These data suggest that quantitative T1? mapping may provide a useful marker for assessing disease progression in HD. The absence of T2 changes suggests that the T1? abnormalities are unlikely owing to altered water content or tissue structure. The established sensitivity of T1? to pH and glucose suggests that these factors are altered in HD perhaps owing to abnormal mitochondrial function.

SUBMITTER: Wassef SN

PROVIDER: S-EPMC4751081 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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T1ρ imaging in premanifest Huntington disease reveals changes associated with disease progression.

Wassef Shafik N SN Wemmie John J Johnson Casey P CP Johnson Hans H Paulsen Jane S JS Long Jeffrey D JD Magnotta Vincent A VA

Movement disorders : official journal of the Movement Disorder Society 20150329 8

<h4>Background</h4>Imaging biomarkers sensitive to Huntington's disease (HD) during the premanifest phase preceding motor diagnosis may accelerate identification and evaluation of potential therapies. For this purpose, quantitative MRI sensitive to tissue microstructure and metabolism may hold great potential. We investigated the potential value of T1ρ relaxation to detect pathological changes in premanifest HD (preHD) relative to other quantitative relaxation parameters.<h4>Methods</h4>Quantita ...[more]

PMID: 25820773

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Project description:Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression.

Dataset Information

T1? imaging in premanifest Huntington disease reveals changes associated with disease progression.

Publications

T1ρ imaging in premanifest Huntington disease reveals changes associated with disease progression.

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