Nicola Z Hobbs, Marina Papoutsi, Aline Delva, Kirsi M Kinnunen, Mitsuko Nakajima, Koen Van Laere, Wim Vandenberghe, Priyantha Herath, Rachael I Scahill
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引用次数: 0
Abstract
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.
亨廷顿氏病(HD)的临床试验越来越多地采用神经成像技术,其目的非常广泛,从选择受试者、安全监控到展示疾病的改变。选择合适的模式和相关分析工具需要慎重考虑。我们代表欧洲多发性硬化症网络成像工作组,就将神经成像纳入 HD 试验的效用和未来前景提出目前的看法。我们介绍了结构性、功能性和弥散性核磁共振成像(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模式,并探讨了如何在 HD 试验中使用神经成像技术,以实现以下目的1)帮助患者选择、增选、分层和安全监控;2)展示生物分布、靶点参与和药效学;3)提供疾病改变的证据;4)了解治疗后的大脑重组。我们还介绍了将研究方法转化为临床试验所面临的挑战,包括设备要求和成本、采集和分析的标准化、患者负担和侵入性以及结果解释。我们的结论是,只要对成像方式、研究设计和分析进行适当的考虑,成像技术在促进有效的 HD 临床试验方面具有巨大的潜力。