Integrating myocardial metabolic imaging and stress myocardial contrast echocardiography to improve the diagnosis of coronary microvascular diseases in rabbits

Background: Persistent challenges associated with misdiagnosis and underdiagnosis of coronary microvascular disease (CMVD) necessitate the exploration of noninvasive imaging techniques to enhance diagnostic accuracy. Therefore, we aimed to integrate multimodal imaging approaches to achieve a higher diagnostic rate for CMVD using high-quality myocardial metabolism imaging (MMI) and myocardial contrast echocardiography (MCE). This combination diagnostic strategy may help address the urgent need for improved CMVD diagnosis. Methods: In this study, we established five distinct pretreatment groups, each consisting of nine male rabbit: a fasted group, a nonfasted group, a sugar load group, an acipimox group, and a combination group of nonfasted rabbits administered insulin. Moreover, positron emission tomography-computed tomography (PET/CT) scan windows were established at 30-, 60-, and 90-minute intervals. We developed 10 CMVD models and conducted a diagnosis of CMVD through an integrated analysis of MMI and MCE, including image acquisition and processing. For each heart segment, we calculated the standardized uptake value (SUV) based on body weight (SUVbw ), as well as certain ratios of SUV including SUV of the heart (SUVheart) to that of the liver (SUVliver) and SUV heart to SUV of the lung (SUVlung). Additionally, we obtained three coronary SUVbw uptake values. To clarify the relationship between SUVbw uptake values and echocardiographic parameters of the myocardial contrast agent more thoroughly, we conducted a comprehensive analysis across different pretreatment protocols. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of each parameter in the context of CMVD. Results: In the context of MMI, the nonfasted-plus-insulin group, as observed during the 60-minute examination, exhibited a noteworthy total 18 F-fluorodeoxyglucose (18F-FDG) 18 F-FDG) uptake of 47.44 +/- 6.53 g/mL, which was found to be statistically different from the other groups. To ascertain the reliability of the results, two double-blind investigators independently assessed the data and achieved a good level of agreement, according to the intraclass correlation coefficient (ICC) (0.957). The SUVbw of the nonfasted-plus-insulin group exhibited a moderate correlation with the microvascular blood flow reserve (MBFR) parameters derived from the MCE examination, as evidenced by a r value of 0.686. For the diagnosis of CMVD disease, the diagnostic accuracy of the combined diagnostic method [area under the curve (AUC) =0.789; 95% confidence interval (CI): 0.705-0.873] was significantly higher than that of the MBFR (AUC =0.697; 95% CI: 0.597-0.797) and SUVbw (AUC =0.715; 95% CI: 0.622-0.807) methods (P<0.05). Conclusions: Our study demonstrated the feasibility of a simple premedication approach involving free feeding and intravenous insulin in producing high-quality gated heart 18 F-FDG PET/CT images in adult male New Zealand white rabbits. This technique holds considerable potential for ischemic heart disease research in rabbits and can enhance CMVD diagnosis via the comprehensive assessment of myocardial metabolism and perfusion.