Beyond the Leak: Advanced MRI Assessment of the Blood-Brain Barrier in Neurodegeneration.

<p>Background: The blood-brain barrier (BBB) is a specialized multicellular interface that maintains the central nervous system's tightly regulated microenvironment. BBB disruption is increasingly recognized as a key feature of neurodegeneration, documented across disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and cerebral small vessel disease (cSVD). While the extent to which BBB breakdown is a cause or consequence of neuronal pathology remains unclear, its pronounced presence in disease states suggests a significant contributory role in progression. Summary: This review provides a neuroradiological overview of advanced MRI approaches for assessing BBB integrity in neurodegenerative diseases. The primary quantitative biomarkers discussed are the volume transfer constant (Ktrans) derived from dynamic contrast-enhanced MRI (DCE), reflecting paracellular gadolinium leakage, and the water exchange rate (kw) from arterial spin labeling (ASL), capturing trans-endothelial water permeability. Disease-specific BBB signatures across AD, PD, and cSVD are systematically described, alongside complementary indirect markers including diffusion MRI, dynamic susceptibility contrast, and vessel architecture imaging. Current technological advances, including ultra-high-field MRI and AI-assisted post-processing, are discussed in relation to their potential to enhance detection sensitivity. With continued technical refinement and standardization, MRI-based BBB metrics are transitioning from research tools into candidate neurovascular biomarkers with growing potential for early diagnosis, treatment monitoring, and longitudinal follow-up. Key Messages: MRI-based BBB imaging represents an emerging neurovascular biomarker under active investigation for future diagnostic and therapeutic applications. DCE and ASL provide complementary BBB metrics (Ktrans, kw), illuminating distinct and complementary facets of barrier dysfunction. BBB disruption is a key and early feature across AD, PD, and cSVD, with disease-specific regional patterns that may guide patient stratification and therapeutic monitoring. Ultra-high-field MRI and AI-assisted post-processing are advancing BBB imaging sensitivity; however, multicenter standardization and normative validation remain critical prerequisites for clinical translation. </p>.