Detection of Early Endothelial Dysfunction by Optoacoustic Tomography

Area of Science:

• Cardiovascular Research
• Medical Imaging
• Vascular Biology

Background:

• Endothelial dysfunction (ED) is a precursor to atherosclerosis, often linked to disturbed blood flow and shear stress.
• Current in vivo models typically focus on late-stage disease, hindering the study of early ED.
• Integrin αvβ3, binding the Arg-Gly-Asp (RGD) motif, is implicated in endothelial cell activation during pathological conditions.

Purpose of the Study:

• To develop and validate a non-invasive imaging method for detecting early endothelial dysfunction.
• To investigate the effects of low and oscillating shear stress on a healthy endothelium in vivo.
• To assess the utility of multispectral optoacoustic tomography (MSOT) with an RGD-mimetic probe for visualizing early ED.

Main Methods:

• A carotid artery cuff model was applied to CD-1 wild-type mice to induce altered shear stress.
• Multispectral optoacoustic tomography (MSOT) was used to detect an intravenously injected RGD-mimetic fluorescent probe longitudinally (2-12 weeks).
• Histological analysis, including immunohistochemistry for αv and CD68, was performed for validation.

Main Results:

• MSOT detected significantly enhanced fluorescent signal intensity in the carotid artery upstream of the cuff, indicating early ED.
• The fluorescent signal was most pronounced 6 and 8 weeks post-surgery.
• Immunohistochemistry confirmed elevated αv expression and the presence of macrophages (CD68) in the affected region, correlating with MSOT findings.

Conclusions:

• MSOT is a sensitive, non-invasive technique capable of delineating early endothelial cell integrity alterations in vivo.
• The study successfully visualized early ED in a healthy endothelium model, highlighting increased integrin αvβ3 expression.
• This approach offers a valuable tool for studying the pathophysiology of endothelial dysfunction and potential therapeutic interventions.