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

Abstract

Background: 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.

Methods: 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.

Results: T1ρ showed a significant increase in the relaxation times in the high-CAP group, as compared to controls, largely in the striatum. The T1ρ 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.

Conclusion: These data suggest that quantitative T1ρ mapping may provide a useful marker for assessing disease progression in HD. The absence of T2 changes suggests that the T1ρ abnormalities are unlikely owing to altered water content or tissue structure. The established sensitivity of T1ρ to pH and glucose suggests that these factors are altered in HD perhaps owing to abnormal mitochondrial function.

Keywords: T1rho; imaging biomarkers; magnetic resonance imaging; premanifest Huntington disease; quantitative imaging.

FIG. 1

T1ρ differences between (A) HiCAP subjects and controls, (B) LoMoCAP subjects and controls, and (C) HiCAP and LoMoCAP subjects. T2 differences between (D) HiCAP subjects and controls, (E) LoMoCAP subjects and controls, and (F) HiCAP and LoMoCAP subjects. T2* differences between (G) HiCAP subjects and controls, (H) LoMoCAP subjects and controls, and (I) HiCAP and LoMoCAP subjects. The Z value maps thresholded at a Z value of 2.3 (P <0.05, corrected at the cluster level) are overlaid on the NAC atlas for reference. The yellow color indicates prolonged relaxation times, while the blue color indicates a shorter relaxation times.