An isolated perfused pig heart model for the development, validation and translation of novel cardiovascular magnetic resonance techniques

Abstract

BackgroundNovel cardiovascular magnetic resonance (CMR) techniques and imaging biomarkers are often validated in small animal models or empirically in patients. Direct translation of small animal CMR protocols to humans is rarely possible, while validation in humans is often difficult, slow and occasionally not possible due to ethical considerations. The aim of this study is to overcome these limitations by introducing an MR-compatible, free beating, blood-perfused, isolated pig heart model for the development of novel CMR methodology.Methods6 hearts were perfused outside of the MR environment to establish preparation stability. Coronary perfusion pressure (CPP), coronary blood flow (CBF), left ventricular pressure (LVP), arterial blood gas and electrolyte composition were monitored over 4 hours. Further hearts were perfused within 3T (n = 3) and 1.5T (n = 3) clinical MR scanners, and characterised using functional (CINE), perfusion and late gadolinium enhancement (LGE) imaging. Perfusion imaging was performed globally and selectively for the right (RCA) and left coronary artery (LCA). In one heart the RCA perfusion territory was determined and compared to infarct size after coronary occlusion.ResultsAll physiological parameters measured remained stable and within normal ranges. The model proved amenable to CMR at both field strengths using typical clinical acquisitions. There was good agreement between the RCA perfusion territory measured by selective first pass perfusion and LGE after coronary occlusion (37% versus 36% of the LV respectively).ConclusionsThis flexible model allows imaging of cardiac function in a controllable, beating, human-sized heart using clinical MR systems. It should aid further development, validation and clinical translation of novel CMR methodologies, and imaging sequences.

Cardiovascular magnetic resonance imaging of isolated perfused pig hearts in a 3T clinical MR scanner

“…All electrical and magnetic parts and thus potentially interfering equip- Schematic view of the perfusion system reproduced from Ref. [10]: roller pump 2 transports the deoxygenated blood through a dialysis module (exchange of metabolites and contrast agent clearance) and then through a blood oxygenator with integrated heat exchanger. The oxygenated blood is then pumped into the heart via roller pump 1…”

“…1) [10]. in brief, it consists of a main circuit to supply the heart with haemoperfusate, a dialysis module to clear out contrast agent and an oxygenator with integrated heat exchanger (Dideco D 100, Mirandola, Modena, italy) to warm and reoxygenate the haemoperfusate.…”

“…This system has already been exploited for validation of quantitative MR perfusion imaging [11] using a dual bolus injection scheme for myocardial blood flow (MBf) quantification [12]. However, the original setup required the electrical system to be within the MR room, which introduced significant background noise [10]. The purpose of the current work was to refine the system to overcome this limitation so that all electrical parts are completely outside the scanner room.…”

“…New sequences, advances in hardware, and post-processing are constantly being developed and require substantial preclinical and translational research before making their way into clinical practice [9]. We have recently introduced an isolated blood perfused heart model to facilitate this process [10]. This model allows control of regional blood flow, oxygenation and workload in order to validate novel MR derived parameters against gold standards, which can expedite translation of new sequences into clinical practice.…”

euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling

“…Based on the point spread function, the images are filtered, followed by segmentation of the vascular structure, which now will allow for computation of flow distribution over the vascular tree into the different compartments of the myocardium. These models will have to be validated by clinical image-based perfusion studies as well as animal studies [67] for which microsphere distribution provides a gold standard ( figure 8). The imaging of the intramural vasculature in post-mortem human hearts will be used to increase our insights into specific vascular abnormalities such as end-stage HF [68].…”