Multimodal Imaging of Blood–Brain Barrier Dysfunction in Parkinson's Disease: From Pathological Mechanisms to Therapeutic Opportunities

Abstract

In Parkinson's disease (PD), blood–brain barrier (BBB) dysfunction is shifting from being viewed as a passive marker of damage to a key pathological driver and potential therapeutic target. Its disruption involves mechanisms such as abnormal α-synuclein transport, tight junction breakdown, inflammatory activation, and vascular remodeling, all of which significantly disturb the neural microenvironment. Imaging technologies are playing an increasingly pivotal role in unraveling these complex processes. Based on current clinical and experimental evidence, this review outlines the major mechanisms of BBB disruption in PD and focuses on recent advances in multiscale imaging techniques for BBB research. It covers super-resolution microscopy, two-photon imaging, MRI, and PET, emphasizing their critical value in mechanistic investigation, functional assessment, and target localization. Multimodal imaging enables cross-scale integration—from nanoscopic to macroscopic levels and from laboratory research to clinical application—and holds promise for building a “mechanism–imaging–intervention” framework that may accelerate the translation from pathophysiological understanding to clinical intervention.