Magnetization transfer imaging in premanifest and manifest Huntington disease

Abstract

Background and purpose: MTI has the potential to detect abnormalities in normal-appearing white and gray matter on conventional MR imaging. Early detection methods and disease progression markers are needed in HD research. Therefore, we investigated MTI parameters and their clinical correlates in premanifest and manifest HD.

Materials and methods: From the Leiden TRACK-HD study, 78 participants (28 controls, 25 PMGC, 25 MHD) were included. Brain segmentation of cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed using FSL's automated tools FAST and FIRST. Individual MTR values were calculated from these regions and MTR histograms constructed. Regression analysis of MTR measures from all gene carriers with clinical measures was performed.

Results: MTR peak height was reduced in both cortical gray (P = .01) and white matter (P = .006) in manifest HD compared with controls. Mean MTR was also reduced in cortical gray matter (P = .01) and showed a trend in white matter (P = .052). Deep gray matter structures showed a uniform pattern of reduced MTR values (P < .05). No differences between premanifest gene carriers and controls were found. MTR values correlated with disease burden and motor and cognitive impairment.

Conclusions: Throughout the brain, disturbances in MTI parameters are apparent in early HD and are homogeneous across white and gray matter. The correlation of MTI with clinical measures indicates the potential to act as a disease monitor in clinical trials. However, our study does not provide evidence for MTI as a marker in premanifest HD.

Fig 1.

MTR histogram for the white matter (C) and cortical gray matter (D), corrected for volume size of the region for 3 groups. An example segmentation acquired with the FAST software showing white matter (red), gray matter (white), and CSF (blue). The subcortical gray matter structures were subtracted from these masks.

Fig 2.

MTR histogram for 6 deep gray matter structures bilaterally, corrected for volume size of the region for 3 groups. Red = caudate nucleus; dark blue = putamen; light green = pallidum; dark green = thalamus; yellow = amygdala; light blue = hippocampus; Con = controls.