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

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.

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 (k_w) 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.

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, k_w), 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.