Nitroxide-enhanced MRI of cardiovascular oxidative stress

Area of Science:

• Cardiovascular Imaging
• Biomedical Engineering
• Molecular Imaging

Background:

• In vivo imaging of oxidative stress is crucial for understanding and treating cardiovascular diseases.
• Myocardial oxidative stress plays a significant role in the pathogenesis of various cardiovascular conditions.
• Current imaging methods for oxidative stress have limitations, necessitating advanced techniques.

Purpose of the Study:

• To evaluate nitroxide-enhanced magnetic resonance imaging (MRI) using 3-carbamoyl-proxyl (3CP) for the detection of myocardial oxidative stress.
• To establish the efficacy of 3CP-enhanced MRI in preclinical models of cardiovascular disease.
• To quantify oxidative stress using the 3CP reduction rate (Kred) as a metric.

Main Methods:

• Three mouse models of cardiac oxidative stress were utilized: angiotensin II (Ang II) infusion, myocardial infarction (MI), and high-fat high-sucrose (HFHS) diet-induced obesity (DIO).
• Mice underwent MRI at various time points following induction of oxidative stress.
• The 3CP reduction rate (Kred) was computed using a tracer kinetic model to assess oxidative stress. Dihydroethidium (DHE) staining was used for validation in the MI model.

Main Results:

• Ang II infusion led to a significant increase in Kred, indicating elevated oxidative stress.
• In the MI model, Kred was significantly elevated in the infarct region at Days 1 and 4 post-MI, correlating with DHE staining results.
• HFHS diet-induced obesity also resulted in a significant increase in Kred after 18 weeks.

Conclusions:

• Nitroxide-enhanced MRI with 3CP provides a noninvasive method for quantifying tissue oxidative stress.
• This technique can be integrated into multiparametric preclinical MRI examinations for cardiovascular research.
• These findings suggest potential for investigating oxidative stress in cardiovascular diseases and evaluating therapeutic interventions.