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 (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P<0.0001) and Δlung-to-muscle ratio (P<0.0001). Hydroxyproline in the heart (P<0.0001) and lungs (P<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P=0.02) and lung (lung-to-muscle ratio, P<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.
结果:在6月龄衰老加速易感小鼠中,横向主动脉缩窄(TAC)引起左心室功能障碍,接受假手术的小鼠的子集。手术三周后,小鼠在4.7T时同时接受PET-MRI。静脉内施用胶原靶向PET和纤维发生磁共振(MR)探针。PET信号计算为心肌或肺与肌肉的比率。从注射前/后的磁共振图像计算出信号强度增加的百分比和Δ肺肌比。TAC小鼠的心脏(P=0.02)和肺(P=0.17)中的大赖氨酸升高对应于心肌磁共振成像百分比信号强度增加(P<0.0001)和Δ肺与肌肉比(P<0.0001)的增加。在TAC小鼠的心脏(P<0.0001)和肺(P<0.01)中羟脯氨酸升高,这对应于心脏的增加(心肌与肌肉的比例,P=0.02)和肺(肺肌比,P<0.001)PET测量。压力-容积环和超声心动图显示左心室重塑不良,函数,TAC小鼠右心室收缩压升高。
结论:施用胶原靶向PET和赖氨酸靶向MR探针导致TAC小鼠心肌和肺中PET磁共振成像信号升高。该研究证明了通过双分子PET-磁共振成像方案检测心肺疾病中的纤维化和纤维化发生的潜力。