Functional magnetic resonance imaging for In Vivo quantification of pulmonary hypertension in the Sugen 5416/hypoxia mouse

Abstract

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures and right heart failure. PAH mouse models are instrumental in understanding disease pathophysiology. However, few methods are available to evaluate right cardiac function in small animals. In this study, magnetic resonance imaging (MRI) was used to measure in vivo cardiac dimensions in the Sugen 5416/hypoxia mouse model. Pulmonary hypertension (PH) was induced in C57BL/6 mice by three weeks of exposure to 10% oxygen and VEGF receptor inhibition (20 mg kg⁻¹ SU5416). Control mice were housed in room air and received vehicle (DMSO). Right ventricle pressures (RVP) were recorded with a pressure-conductance transducer. Short axis contiguous 1 mm thick slices were acquired through the heart and great vessels using a Fast Low Angle SHot (FLASH)-cine sequence. Thirteen images were collected throughout each cardiac cycle. RV systolic pressure was elevated in PH mice (23.6 ± 6 vs. 41.0 ± 11 mmHg, control vs. PH, respectively; P < 0.001, n = 5–11). RV wall thickness was greater in PH mice than control at end-diastole (0.30 ± 0.05 vs. 0.48 ± 0.06 mm, control vs. PH, respectively; P < 0.01, n = 6), but measurements were not different at end-systole (control vs. PH, 0.59 ± 0.11 vs. 0.70 ± 0.11 mm, respectively). RV ejection fraction was decreased in PH mice (72 ± 3 % vs. 58 ± 5 %, control vs. PH, respectively, P < 0.04, n = 6). These data demonstrate that MRI is a precise method to longitudinally monitor right ventricle remodeling and cardiac output in mice models of PH.

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