Tracer kinetic model detecting heterogeneous blood–brain barrier permeability to water and contrast agent in Alzheimer's disease and dementia with Lewy bodies
Ziming Xu, Yong Ji, Wen Chen, Jinghuan Gan, Zhichao Chen, Rui Li, Xiaoqi Lin, Jiaqi Dou, Yajie Wang, Shuai Liu, Zhihong Shi, Hao Wu, Hao Lu, Huijun Chen
Abstract
INTRODUCTION: Blood-brain barrier (BBB) breakdown is essential in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), whereas the variability in BBB permeability to water and contrast agent is less clear. METHODS: We investigated BBB permeability to water and contrast agent simultaneously using a novel tracer kinetic model for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 42 AD patients, 22 DLB patients, and 22 healthy controls. All participants underwent clinical, cognitive, and MRI assessments. RESULTS: AD patients exhibited a significant reduction in the water exchange rates across the BBB, whereas DLB patients showed a significant increase in BBB permeability to contrast agent. Moreover, BBB permeability to both water and contrast agent in multiple brain regions demonstrated correlations with clinical severity. DISCUSSION: The simultaneous evaluation of BBB permeability to water and contrast agent based on the proposed model highlights the heterogeneous patterns of BBB breakdown in AD and DLB. HIGHLIGHTS: We measured blood-brain barrier (BBB) permeability to water and contrast agent based on dynamic contrast-enhanced magnetic resonance imaging. Alzheimer's disease (AD) is characterized by lower water exchange rates across the BBB. Dementia with Lewy bodies exhibits higher BBB permeability to contrast agent. BBB permeability is related to cognitive impairment and disease burden. BBB permeability to water was negatively associated with that to contrast agent.