Sala Arianna, Perani Daniela
Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy.
Division of Neuroscience, Faculty of Psychology, San Raffaele Scientific Institute (IRCCS), Milan, Italy.
Front Neurosci. 2019 Jun 14;13:617. doi: 10.3389/fnins.2019.00617. eCollection 2019.
Positron emission tomography (PET) represents a unique molecular tool to get access to a wide spectrum of biological and neuropathological processes, of crucial relevance for neurodegenerative conditions. Although most PET findings are based on massive univariate approaches, in the last decade the increasing interest in multivariate methods has paved the way to the assessment of unexplored cerebral features, spanning from resting state brain networks to whole-brain connectome properties. Currently, the combination of molecular neuroimaging techniques with multivariate connectivity methods represents one of the most powerful, yet still emerging, approach to achieve novel insights into the pathophysiology of neurodegenerative diseases. In this review, we will summarize the available evidence in the field of PET molecular connectivity, with the aim to provide an overview of how these studies may increase the understanding of the pathogenesis of neurodegenerative diseases, over and above "traditional" structural/functional connectivity studies. Considering the available evidence, a major focus will be represented by molecular connectivity studies using [18F]FDG-PET, today applied in the major neuropathological spectra, from amyloidopathies and tauopathies to synucleinopathies and beyond. Pioneering studies using PET tracers targeting brain neuropathology and neurotransmission systems for connectivity studies will be discussed, their strengths and limitations highlighted with reference to both applied methodology and results interpretation. The most common methods for molecular connectivity assessment will be reviewed, with particular emphasis on the available strategies to investigate molecular connectivity at the single-subject level, of potential relevance for not only research but also diagnostic purposes. Finally, we will highlight possible future perspectives in the field, with reference in particular to newly available PET tracers, which will expand the application of molecular connectivity to new, exciting, unforeseen possibilities.
正电子发射断层扫描（PET）是一种独特的分子工具，可用于研究广泛的生物和神经病理过程，这对于神经退行性疾病至关重要。尽管大多数PET研究结果基于大量单变量方法，但在过去十年中，对多变量方法的兴趣日益增加，为评估未探索的脑特征铺平了道路，从静息态脑网络到全脑连接组特性。目前，分子神经成像技术与多变量连接方法的结合是获得神经退行性疾病病理生理学新见解的最强大但仍在不断发展的方法之一。在本综述中，我们将总结PET分子连接领域的现有证据，旨在概述这些研究如何在“传统”结构/功能连接研究之外，增加对神经退行性疾病发病机制的理解。考虑到现有证据，主要重点将是使用[18F]FDG-PET的分子连接研究，该研究目前应用于主要的神经病理谱，从淀粉样病变和tau病变到突触核蛋白病变等。将讨论使用针对脑病理和神经传递系统的PET示踪剂进行连接研究的开创性研究，并参考应用方法和结果解释突出其优势和局限性。将回顾分子连接评估的最常见方法，特别强调在单受试者水平研究分子连接的可用策略，这不仅对研究而且对诊断目的都具有潜在相关性。最后，我们将强调该领域可能的未来前景，特别是参考新出现的PET示踪剂，这将把分子连接的应用扩展到新的、令人兴奋的、不可预见的可能性。
