In vivo assessment of heart function under chronic hypoxic stress with volumetric optoacoustic tomography

Abstract

Chronic hypoxia in pulmonary diseases is known to have a severe negative impact on heart function, including right heart hypertrophy, increased workload on the heart and arrhythmia. Yet, the direct effect of the chronic hypoxic environment on the cardiovascular system is still not fully understood. Usual pre-clinical analytic methods analysing this effect are limited to ex vivo histology or highly invasive approaches such as right heart catheterisation, which inevitably interfere with cardiac tissue. In this work, we propose volumetric optoacoustic tomography as a method for assessing heart function in response to chronic hypoxia non-invasively. Hypoxic and normoxic murine hearts were imaged in vivo at high temporal (100 Hz) and spatial resolution (200 μm). Analysis of the murine models on a beat-to-beat scale enabled identifying and characterizing arrhythmic events in hypoxic models. In addition, blood flow was tracked using indocyanide green (ICG) contrast agent, which revealed a clear difference in the pulmonary transit time (PTT) between the hypoxic and normoxic models. Validation for presence of hypoxia in the lungs was carried out by α-smooth muscle actin staining for muscularization of the pulmonary vasculature. We expect that the novel capabilities offered by volumetric optoacoustic tomography for analysing impaired heart function under hypoxic conditions in pre-clinical models will provide important insights into early diagnosis and treatment methods for pulmonary diseases.