Quantitative 7T phase imaging in premanifest Huntington disease

Abstract

Background and purpose: In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease.

Materials and methods: Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift.

Results: Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function.

Conclusions: Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease.

Fig 1.

A, ROIs are extracted automatically from 3T T1-weighted images by using FSL; the segmented caudate nuclei from 1 subject are shown in light blue. B, Caudate ROIs are automatically coregistered with the 7T data and overlaid onto the phase images. C, PLIC ROIs drawn manually (thin region drawn on each side of the brain in white) on 7T phase images. Mean PLIC phase was used for normalization in the construction of LFS maps in each patient.

Fig 2.

Magnified phase image centered on the basal ganglia in a representative subject with pmHD. The numeric values of phase reflect the composite effects of iron concentration, deoxyhemoglobin within veins, myelin, and tissue microstructure.

Fig 3.

Boxplots comparing caudate volume (left), normalized by the total intracranial volume (cubic millimeter/cubic millimeter); and LFS (right), normalized by mean PLIC phase (in parts per billion), in subjects with pmHD and controls. Caudate LFS and normalized volume are depicted for the interhemispheric average value (dark gray), the right caudate nucleus (intermediate gray), and the left caudate nucleus (light gray).

Fig 4.

Scatterplots comparing caudate LFS with normalized caudate volume (left) and with CAP_S (right) for subjects with pmHD and controls. In the left plot, triangles and circles refer to subjects with pmHD and controls, respectively. There was no correlation between caudate LFS and caudate volume. In the right plot, subjects in the low (x), medium (□), and high (♢) CAP_S groups. There is a strong positive correlation between CAP_S and caudate LFS (R² = 0.61, P = .003).

Fig 5.

Scatterplots illustrating relationships between LFS and EXAMINER indices, including Executive Composite (top left), Fluency Factor (top right), Cognitive Control Factor (bottom left), and Working Memory Factor (bottom right). After correction for multiple comparisons, correlations were not significant but confirmed trends for Executive Composite (R² = 0.32, P = .031) and Working Memory Factor (R² = 0.35, P = .018). Circles (○) and triangles (▴) refer to controls and subjects with pmHD, respectively.