Structural MRI in Huntington's disease and recommendations for its potential use in clinical trials

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★ Structural MRI has the potential to assess progression in clinical trials. ★ The most promising biomarkers in HD are striatal and white matter atrophy. ★ Consideration of image acquisition, processing and statistical design is essential. ★ Appropriate reporting of study design is vital to allow evaluation of the literature.

Huntington's disease (HD) results in progressive impairment of motor and cognitive function and neuropsychiatric disturbance. There are no disease-modifying treatments available, but HD research is entering a critical phase where promising disease-specific therapies are on the horizon. Thus, a pressing need exists for biomarkers capable of monitoring progression and ultimately determining drug efficacy. Neuroimaging provides a powerful tool for assessing disease progression. However, in order to be accepted as biomarkers for clinical trials, imaging measures must be reproducible, robust to scanner differences, sensitive to disease-related change and demonstrate a relationship to clinically meaningful measures. We provide a review of the current structural imaging literature in HD and highlight inconsistencies between studies. We make recommendations for the standardisation of reporting for future studies, such as appropriate cohort characterisation and documentation of methodologies to facilitate comparisons and inform trial design. We also argue for an intensified effort to consider issues highlighted here so that we have the best chance of assessing the efficacy of the therapeutic benefit in forestalling this devastating disease.

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