HD Research Centre, UCL Institute of Neurology, UCL, London, UK.
IXICO plc, London, UK.
J Huntingtons Dis. 2024;13(2):163-199. doi: 10.3233/JHD-240016.
Neuroimaging is increasingly being included in clinical trials of Huntington's disease (HD) 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. On behalf of the EHDN Imaging Working Group, we present current opinion on the utility and future prospects for inclusion of neuroimaging in HD trials. Covering the key imaging modalities of structural-, functional- and diffusion- MRI, perfusion imaging, positron emission tomography, magnetic resonance spectroscopy, and magnetoencephalography, we address how neuroimaging can be used in HD trials to: 1) Aid patient selection, enrichment, stratification, and safety monitoring; 2) Demonstrate biodistribution, target engagement, and pharmacodynamics; 3) Provide evidence for disease modification; and 4) Understand brain re-organization following therapy. We also present the challenges of translating research methodology into clinical trial settings, including equipment requirements and cost, standardization of acquisition and analysis, patient burden and invasiveness, and interpretation of results. We conclude, that with appropriate consideration of modality, study design and analysis, imaging has huge potential to facilitate effective clinical trials in HD.
神经影像学越来越多地被纳入亨廷顿病(HD)的临床试验中,其目的广泛,从参与者选择和安全性监测,到疾病修饰的证明。选择适当的方式和相关的分析工具需要仔细考虑。代表 EHDN 成像工作组,我们提出了目前对神经影像学在 HD 试验中的应用的意见和未来的前景。涵盖结构、功能和弥散 MRI、灌注成像、正电子发射断层扫描、磁共振波谱和脑磁图等主要成像方式,我们探讨了神经影像学如何在 HD 试验中用于:1)辅助患者选择、富集、分层和安全性监测;2)证明生物分布、靶点结合和药效学;3)提供疾病修饰的证据;以及 4)了解治疗后的大脑重新组织。我们还介绍了将研究方法转化为临床试验环境所面临的挑战,包括设备要求和成本、采集和分析的标准化、患者负担和侵袭性以及结果的解释。我们的结论是,通过适当考虑方式、研究设计和分析,成像具有巨大的潜力,可以促进 HD 的有效临床试验。
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