Neuropathological studies have revealed the devastating effect of Huntington’s disease on the brain at postmortem, but neuroimaging presents us with the opportunity to visualise these pathological effects in vivo, even from the very earliest premanifest stages.

Structural MRI provides high resolution images of the brain, allowing us to identify disease-related volumetric differences at the macroscopic level. Using such techniques, striatal atrophy has been highlighted up to fifteen years prior to symptom onset and there is increasing recognition that white matter degeneration is also an early pathological feature. Large-scale observational studies such as TRACK-HD and PREDICT-HD have demonstrated that these measures track disease progression over time and therefore have potential utility as biomarkers with realistic sample sizes for clinical trials.

Brain activity can be assessed using fMRI. fMRI measures blood flow either at rest or during performance of a task, and has highlighted areas showing increased or decreased blood flow in HD gene carriers. Work is currently being undertaken to assess the consistency of fMRI over time and also at different imaging sites.

PET can be used to identify a variety of brain functions: FDG-PET measures glucose metabolism which is indicative of brain activity; RAC-PET identifies dopamine receptor sites and PK-PET highlights microglial activation. Novel ligands suitable for binding to other important structures within the cell are becoming available and PET is a promising technique which is likely to show relatively rapid and specific response to treatments targeting these particular processes.

There are a number of other neuroimaging techniques aimed at assessing different aspects of the pathological process e.g. diffusion-weighted imaging for white matter microstructure, magnetic resonance spectroscopy to measure neuronal health. I will provide an overview of a range of neuroimaging techniques, considering what they can tell us about the natural history of HD as well as their potential utility for future clinical trials.

Support RS is supported by the CHDI/High Q Foundation.