Development and validation of cardiac diffusion weighted magnetic resonance imaging for the diagnosis of myocardial injury in small animal models

Abstract Cardiac diffusion weighted-magnetic resonance imaging (DWI) has slowly developed due to its technical difficulties. However, this limitation could be overcome by advanced techniques, including a stimulated echo technique and a gradient moment nulling technique. This study aimed to develop and validate a high-order DWI sequence, using echo-planar imaging (EPI) and second-order motion-compensated (M012) diffusion gradient applied to cardiac imaging in small-sized animals with fast heart and respiratory rates, and to investigate the feasibility of cardiac DWI, diagnosing acute myocardial injury in isoproterenol-induced myocardial injury rat models. The M012 diffusion gradient sequence was designed for diffusion tensor imaging of the rat myocardium and validated in the polyvinylpyrrolidone phantom. Following sequence optimization, 23 rats with isoproterenol-induced acute myocardial injury and five healthy control rats underwent cardiac MRI, including cine imaging, T1 mapping, and DWI. Diffusion gradient was applied using a 9.4-T MRI scanner (Bruker, BioSpec 94/20, gradient amplitude = 440 mT/m, maximum slew rate = 3440 T/m/s) with double gating (electrocardiogram and respiratory gating). Troponin I was used as a serum biomarker for myocardial injury. Histopathologic examination of the heart was subsequently performed. The developed DWI sequence using EPI and M012 provided the interpretable images of rat hearts. The apparent diffusion coefficient (ADC) values were significantly higher in rats with acute myocardial injury than in the control group (1.847 ± 0.326 * 10 –3 mm 2 /s vs. 1.578 ± 0.144 * 10 –3 mm 2 /s, P < 0.001). Troponin I levels were increased in the blood samples of rats with acute myocardial injury ( P < 0.001). Histopathologic examinations detected myocardial damage and subendocardial fibrosis in rats with acute myocardial injury. The newly developed DWI technique has the ability to detect myocardial injury in small animal models, representing high ADC values on the myocardium with isoproterenol-induced injury.