Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

BACKGROUND

Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model.

METHODS AND RESULTS

Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (=0.02) and lungs (=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (<0.0001) and Δlung-to-muscle ratio (<0.0001). Hydroxyproline in the heart (<0.0001) and lungs (<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, =0.02) and lung (lung-to-muscle ratio, <0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice.

CONCLUSIONS

Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.