SCMR 22nd Annual Scientific Sessions
Previous studies have used large animal models for validation of diffusion tensor cardiovascular magnetic resonance (DT-CMR) [1,2] and small animal isolated perfused hearts have been used to evaluate cardiac microstructure in relaxed and contracted states. In this work, we develop a large animal isolated perfused beating heart model providing microstructure in arrested and beating hearts in contracted and relaxed states.
Hearts were harvested from large white pigs (~60-80kg) by a specialist surgical team at a clinical standard facility based on a heart transplant protocol, with a long section of intact aorta. Hearts were arrested and protected using cardioplegia and topical cooling with a cold ischemic time of ~2.5-3hours prior to imaging.
The aorta was attached to a custom 3D printed cannula in the magnet room and Langendorff perfused with a modified Tyrode’s solution at room temperature (Figure 1). A custom perfusion tubing set was used with a heat-exchanger/membrane oxygenator located in the control room and a secondary heat exchanger placed on the scanner bed. A flexible tube through the mitral valve was used to relieve excess intracavity left ventricular pressure. Perfusion flow and temperature were increased gradually (38°C, ~350ml/min). Defibrillation with 10-30J was performed for ventricular fibrillation. Once the hearts began to contract, autologous washed blood (0.5-1L whole) was added to the perfusate. Hearts were paced above the intrinsic rate.
The beating heart was transferred to a custom 3D printed chamber holding the heart at the magnet isocentre and allowing a small surface coil to be wrapped around. Cine, DT-CMR and parametric mapping were performed on the beating heart, triggered from the pacing box. Pacing was then stopped and high potassium Tyrode’s perfusate was used to arrest hearts in a relaxed state. Next, sodium-free high-lithium perfusion induced contracture. DT-CMR and parametric mapping were repeated in both arrested states.
Oil filled tubes within the bed of the imaging chamber provided fiducial markers, allowing blocks of tissue to be cut in the plane of the DT-CMR data. Histological sections were cut from these blocks (100µm for 3D confocal imaging, 10µm for widefield).
Hearts were harvested from 10 pigs and 6 were successfully established in beating heart mode (success record, S=success, F=failure: FFSFFSSSSS). Example video is available at https://imperialcollegelondon.box.com/v/SCMR2019 and stills are shown in Figure 2. Initial DT-CMR results and corresponding 3D histology are shown in Figure 3.
An MR compatible isolated perfused heart preparation has been established to enable imaging in beating and arrested states in centres without pre-clinical facilities. Microstructural imaging can be performed in both contracted and relaxed states, with co-localised histology for validation. Future work will address the effects of cardiac edema.