Abstract

Microvascular disease is frequently found in major pathologies affecting vital organs, such as the brain, heart, and kidneys. While imaging modalities, such as ultrasound, computed tomography, single photon emission computed tomography, and magnetic resonance imaging, are widely used to visualize vascular abnormalities, the ability to non-invasively assess an organ’s total vasculature, including microvasculature, is often limited or cumbersome. Previously, we have demonstrated proof of concept that non-invasive imaging of the total mouse vasculature can be achieved with 18F-fluorodeoxyglucose (18F-FDG)-labeled human erythrocytes and positron emission tomography/computerized tomography (PET/CT). In this work, we demonstrate that changes in the total vascular volume of the brain and left ventricular myocardium of normal rats can be seen after pharmacological vasodilation using 18F-FDG-labeled rat red blood cells (FDG RBCs) and microPET/CT imaging. FDG RBC PET imaging was also used to approximate the location of myocardial injury in a surgical myocardial infarction rat model. Finally, we show that FDG RBC PET imaging can detect relative differences in the degree of drug-induced intra-myocardial vasodilation between diabetic rats and normal controls. This FDG-labeled RBC PET imaging technique may thus be useful for assessing microvascular disease pathologies and characterizing pharmacological responses in the vascular bed of interest.

Highlights

  • Microvascular disease (MVD) is a type of vascular disorder affecting the arterioles, venules, and capillaries of the vasculature [1,2]

  • We have previously shown that FDG-labeled human red blood cells (RBCs) can be used to visualize the total body vasculature of immunocompromised mice with a small animal microPET/computed tomography (CT) scanner [28]

  • Similar to results shown in our prior publication, we found that after intravenous injection of FDG-labeled rat RBCs, there is diffuse, intense tracer activity throughout the rat brain volume on positron emission tomography (PET) imaging (Figure 1)

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Summary

Introduction

Microvascular disease (MVD) is a type of vascular disorder affecting the arterioles, venules, and capillaries of the vasculature [1,2]. MVD can be found in vital organs, such as the brain, heart, and kidneys, in various diseases, including atherosclerosis, dementia, and stroke [3–7]. In the heart, coronary microvascular dysfunction (CVD) can occur with or without obstructive epicardial coronary artery disease, leading to ischemia and angina [8–11]. Imaging techniques, such as coronary flow reserve (CFR), fractional flow reserve (FFR), and index of microcirculatory resistance (IMR), are accepted as measures of myocardial blood flow and even microvascular disease; but are essentially limited to invasive coronary angiography [12–14]. Ultrasound microbubble imaging has been used to assess blood flow and velocity in multiple organs but is dependent on adequate

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