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Multicenter Study
. 2017 Oct;38(10):5035-5050.
doi: 10.1002/hbm.23713. Epub 2017 Jun 28.

Mapping the Order and Pattern of Brain Structural MRI Changes Using Change-Point Analysis in Premanifest Huntington's Disease

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Free PMC article
Multicenter Study

Mapping the Order and Pattern of Brain Structural MRI Changes Using Change-Point Analysis in Premanifest Huntington's Disease

Dan Wu et al. Hum Brain Mapp. .
Free PMC article

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset ("premanifest" period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, "change-points"), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035-5050, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: atlas-based segmentation; brain atrophy; change-point analysis; diffusion tensor MRI; premanifest HD; spatiotemporal order.

Figures

Fig. 1
Fig. 1
Brain regions that showed significant group differences in volume (thresholded by 5% FDR) between the controls and the low, median, and high CAP premanifest HD groups, mapped to a T1-weighted image. The color maps represent the percentage volume differences (mean group difference normalized by the mean of the controls) in those regions.
Fig. 2
Fig. 2
Change-point analysis of the volumetric data in several representative brain structures that showed significant change points. The blue dots represent the volumetric measurements after correcting for age, sex, and intracranial volumes in Equation 1; the black curves are the fitted data based on the change-point term (second term in Equation 1); and the red lines located at the transition position of the black curves indicate the change points.
Fig. 3
Fig. 3
(A) Volume-based change points from all brain structures mapped to a T1-weighted image. Only the regions with significant change points (thresholded by 5% FDR) are shown and the colors indicate the change point values in units of CAP score. (B) Rates of volumetric change (in units of percentage volume change per CAP) in regions with significant change points, mapped to a T1-weighted image. The change rate corresponds to β in Equation 1.
Fig. 4
Fig. 4
(A) Regions that showed significant group differences (thresholded by 5% FDR) in mean diffusivity (MD) between the controls and median- and high- CAP premanifest HD groups. (B) Regions that showed significant group differences in fractional anisotropy (FA) between the controls and high CAP group. The regional group differences were mapped to an FA atlas (JHU DTI brain template). The color maps represent the percentage MD increase with respect to the controls in those regions.
Fig. 5
Fig. 5
Change point analysis of the MD data in the major brain regions that show significant change points. The blue dots represent the MD measurements after correcting for age, sex, and intracranial volumes in Equation 2; the black curves are the fitted data based on the change-point term (second term in Equation 2); and the red lines located at the transition position of the black curves indicate the change points.
Figure 6
Figure 6
(A) MD-based change points from all brain structures mapped to a FA image. Only the regions with significant change points (thresholded by 5% FDR) are shown and the colors indicate the change point values in units of CAP score. (B) Rates of MD increase (in units of percentage MD increase per CAP) in regions with significant change points, mapped to an FA atlas (JHU DTI brain template). The change rate corresponds to β in Equation 2.

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