What is the clinical evidence from this study?

Study design: Other. Population: Endothelial dysfunction and multiple cardiovascular co-morbidities (n=32). Intervention: Multiple cardiovascular co-morbidities (ZSF1 Obese phenotype) vs. ZSF1 Lean phenotype. Primary outcome: Mean Cerebral Blood Flow (CBF) in the hippocampus at 20 weeks of age (d = 0.48, p=0.0003).

October 19, 2024Open Access

A timeline study on vascular co-morbidity induced cerebral endothelial dysfunction assessed by perfusion MRI

Key Result

ZSF1 Obese rats exhibited early cerebral hyperperfusion, with significantly increased cerebral blood flow in the hippocampus at 20 weeks of age (p=0.0003, d=0.48) compared to Lean controls.

Structured PICO

Does Arterial Spin Labeling (ASL) MRI detect early cerebral hyperperfusion in a rat model of cardiovascular comorbidities?

Population

32 male ZSF1 Lean and Obese rats were evaluated at 14, 20, and 30 weeks of age to assess cerebral endothelial dysfunction using perfusion MRI.

Exposure

Perfusion MRI measurements (Arterial Spin Labeling, Intravoxel Incoherent Motion, and Dynamic Susceptibility Contrast enhanced MRI)

Comparator

ZSF1 Lean rats (control group) and invasive immunohistochemistry

Outcome

Early pathological alterations in the cerebral vasculature (Cerebral Blood Flow and Blood Brain Barrier permeability)surrogate

Arterial Spin Labeling (ASL) MRI can detect early functional alterations, such as regional cerebral hyperperfusion, preceding morphological vascular changes in a rat model of cardiovascular comorbidities.

Main Result

Standardized Mean Difference: 0.48

p-value: p=0.0003

Limitations

Application of single delay ASL instead of more advanced multi-delay (p)CASL methods
Lack of an additional non-invasive readout of BBB leakage, such as Dynamic Contrast Enhanced (DCE) MRI

Abstract

Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction. This study primarily aimed to identify which among various perfusion MRI methodologies could be effectively utilized to non-invasively identify early pathological alterations as a result of endothelial dysfunction. We compared these perfusion MRI measurements to invasive immunohistochemistry to detect early pathological alterations in the cerebral vasculature of a rat model of multiple cardiovascular co-morbidities (the ZSF1 Obese rat) at several stages of the cerebrovascular pathology. We observed cerebral hyperperfusion, expressed by increased Cerebral Blood Flow (CBF) and increased BBB permeability in the ZSF1 Obese rats, at an early stage of disease development. The increase in CBF observed with Arterial Spin Labeling (ASL) was lost during later stages of disease progression. These findings are in line with recent clinical findings in early stages of Alzheimer's disease (AD), that also show early increases in CBF. • Cerebral hyperperfusion detected by ASL in ZSF1-O rats at 20 weeks. • Hippocampus, shows a more significant increase in CBF than other regions. • Increased BBB permeability and increased CBF coincide in ZSF1-O rats. • Functional alterations precede morphological changes in vascular network. • ASL could be a diagnostic tool for early detection of neurodegenerative disorders.

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