Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR...

Area of Science:

• Cardiovascular Research
• Medical Imaging
• Vascular Biology

Background:

• Atherosclerosis is an inflammatory vascular disease involving endothelial dysfunction and plaque buildup.
• Extracellular matrix (ECM)-associated proteins like albumin are implicated in atherosclerosis development.
• Current diagnostic methods may not fully capture the dynamic inflammatory processes within atherosclerotic plaques.

Purpose of the Study:

• To investigate the feasibility of using two molecular MRI probes for simultaneous assessment of intraplaque albumin and inflammation in atherosclerosis.
• To evaluate the efficacy of a combined albumin-specific (gadofosveset) and macrophage-specific (ferumoxytol) MRI approach.
• To correlate MRI findings with histological assessments of plaque composition.

Main Methods:

• Apolipoprotein E-deficient (ApoE)-mice on a high-fat diet (HFD) were used, with one group receiving pravastatin treatment.
• T1- and T2*-weighted MRI was performed before and after administration of gadofosveset and ferumoxytol.
• Post-MRI analysis included laser ablation inductively coupled plasma mass spectrometry and histology (e.g., Perls' Prussian blue stain).

Main Results:

• MRI signal enhancement post-gadofosveset correlated significantly with albumin staining (R² = 0.78).
• T2*-weighted MRI signal loss post-ferumoxytol correlated significantly with Perls' Prussian blue staining (R² = 0.83).
• Pravastatin treatment reduced inflammation and intraplaque albumin, as detected by MRI and histology. No interference between the two contrast agents was observed.

Conclusions:

• Multi-target MRI combining ferumoxytol and gadofosveset is a feasible and promising method for atherosclerosis assessment.
• This approach allows simultaneous evaluation of endothelial damage (albumin deposition) and inflammation (macrophage infiltration).
• The combined MRI technique holds potential for improved diagnosis and monitoring of atherosclerosis treatment response.