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E15 How useful is neuroimaging in clinical trials of Huntington’s disease? Current opinion from the ehdn imaging working group
  1. Nicola Hobbs1,
  2. Marina Papoutsi1,2,
  3. Aline Delva3,4,
  4. Wim Vandenberghe3,4,
  5. Koen Van Laere5,6,
  6. Mitsuko Nakajima1,
  7. Kirsi Kinnunen2,
  8. Rachael I Scahill1
  1. 1Department of Neurodegenerative disease, UCL Institute of Neurology, UCL, London, UK
  2. 2IXICO Plc, London, UK
  3. 3Department of Neurosciences, KU Leuven, Belgium
  4. 4Department of Neurology, University Hospitals Leuven, Belgium
  5. 5Department of Imaging and Pathology, KU Leuven, Belgium
  6. 6Department of Nuclear Medicine, University Hospitals Leuven, Belgium


Background Neuroimaging is increasingly being included in Huntington’s disease (HD) clinical trials for a wide range of purposes from participant selection and safety monitoring, through to demonstration of disease modification. Selection of the appropriate modality and associated analysis tools requires careful consideration.

Aims We present current opinion on the utility and prospects for inclusion of neuroimaging in HD trials.

Methods An EHDN Imaging Working Group subgroup was formed to include experts in the key imaging modalities: structural, functional and diffusion MRI, Magnetic Resonance Spectroscopy, Magnetoencephalography and Positron Emission Tomography (PET). We examined the utility of each modality for clinical trials to: aid patient selection, enrichment, stratification & safety monitoring; demonstrate biodistribution, target engagement and pharmacodynamics, and provide evidence for disease modification. We discussed the challenges of translating methodology into large clinical trial settings, including: equipment requirements and cost; standardisation of acquisition and analysis; patient burden and interpretation of results.

Outcomes Structural MRI is the most widely applied and reliable neuroimaging modality in HD trials; selecting appropriate image-analysis software and quality control measures is of paramount importance. PET Radiotracers targeting aggregated mHTT, currently in development, would represent a real breakthrough in the evaluation of cerebral target engagement in mHTT-lowering clinical trials. Interpreting imaging results in the presence of a therapeutic intervention can be much more complex than in observational studies. Examining multi-modal readouts and including additional imaging timepoints may aid interpretation.

Conclusions With appropriate consideration of modality and analysis tools, imaging has huge potential to facilitate effective clinical trials in HD.

  • Neuroimaging
  • clinical trials
  • current opinion

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