Following the impressive progress in the treatment of relapsing–remitting multiple sclerosis (MS), the major challenge ahead is the development of treatments to prevent or delay the irreversible accumulation of clinical disability in progressive forms of the disease. The substrate of clinical progression is neuro-axonal degeneration, and a deep understanding of the mechanisms that underlie this process is a precondition for the development of therapies for progressive MS. PET imaging involves the use of radiolabelled compounds that bind to specific cellular and metabolic targets, thereby enabling direct in vivo measurement of several pathological processes. This approach can provide key insights into the clinical relevance of these processes and their chronological sequence during the disease course. In this Review, we focus on the contribution that PET is making to our understanding of extraneuronal and intraneuronal mechanisms that are involved in the pathogenesis of irreversible neuro-axonal damage in MS. We consider the major challenges with the use of PET in MS and the steps necessary to realize clinical benefits of the technique. In addition, we discuss the potential of emerging PET tracers and future applications of existing compounds to facilitate the identification of effective neuroprotective treatments for patients with MS.

继复发缓解型多发性硬化症 (MS) 的治疗取得令人瞩目的进展之后，未来的主要挑战是开发治疗方法以预防或延缓疾病进展形式中临床残疾的不可逆累积。临床进展的基础是神经轴突变性，深入了解这一过程背后的机制是开发进行性 MS 疗法的先决条件。PET 成像涉及使用与特定细胞和代谢靶标结合的放射性标记化合物，从而能够直接对多种病理过程进行体内测量。这种方法可以提供对这些过程的临床相关性及其在疾病过程中的时间顺序的重要见解。在这篇评论中，我们专注于 PET 对我们理解参与 MS 不可逆神经轴突损伤发病机制的神经元外和神经元内机制的贡献。我们考虑了在 MS 中使用 PET 所面临的主要挑战以及实现该技术的临床益处所必需的步骤。此外，我们还讨论了新兴 PET 示踪剂的潜力和现有化合物的未来应用，以促进确定对 MS 患者有效的神经保护治疗。