Abstract
Exposure to chronic hypoxia results in pulmonary hypertension characterized by increased vascular resistance and pulmonary vascular remodeling, changes in functional parameters of the pulmonary vasculature, and right ventricular hypertrophy, which can eventually lead to right heart failure. The underlying mechanisms of hypoxia-induced pulmonary hypertension have still not been fully elucidated while no curative treatment is currently available. Commonly employed pre-clinical analytic methods are largely limited to invasive studies interfering with cardiac tissue or otherwise ex vivo functional studies and histopathology. In this work, we suggest volumetric optoacoustic tomography (VOT) for non-invasive assessment of heart function in response to chronic hypoxia. Mice exposed for 3 consecutive weeks to normoxia or chronic hypoxia were imaged in vivo with heart perfusion tracked by VOT using indocyanide green contrast agent at high temporal (100 Hz) and spatial (200 µm) resolutions in 3D. Unequivocal difference in the pulmonary transit time was revealed between the hypoxic and normoxic conditions concomitant with the presence of pulmonary vascular remodeling within hypoxic models. Furthermore, a beat-to-beat analysis of the volumetric image data enabled identifying and characterizing arrhythmic events in mice exposed to chronic hypoxia. The newly introduced non-invasive methodology for analysis of impaired pulmonary vasculature and heart function under chronic hypoxic exposure provides important inputs into development of early diagnosis and treatment strategies in pulmonary hypertension.
Highlights
Pulmonary hypertension (PH) is a disorder characterized by pulmonary vascular remodeling, right ventricular hypertrophy and increased pulmonary arterial pressure
Even though cardio-respiratory gating in magnetic resonance imaging (MRI) and X-ray computed tomography (CT) may enable characterizing some of the in vivo functional cardiac parameters, those methods are generally ill-suited for cardiac imaging due to insufficient temporal resolution when performing true 3D whole-heart imaging at high spatial resolution[15,16]
The volumetric optoacoustic tomography (VOT) data was acquired for each indocyanine green (ICG) injection for a total duration of 50 s (5000 frames), which is a sufficient amount of time to track blood flow through the pulmonary circuit
Summary
Pulmonary hypertension (PH) is a disorder characterized by pulmonary vascular remodeling, right ventricular hypertrophy and increased pulmonary arterial pressure. Even though cardio-respiratory gating in magnetic resonance imaging (MRI) and X-ray computed tomography (CT) may enable characterizing some of the in vivo functional cardiac parameters, those methods are generally ill-suited for cardiac imaging due to insufficient temporal resolution when performing true 3D whole-heart imaging at high spatial resolution[15,16]. To this end, ultrasound (US), and more recently ultrafast US, are arguably the most suitable modalities for cardiac imaging in murine models. We demonstrate the capabilities of a recently developed real-time three-dimensional OA imaging system for analyzing heart function in vivo and non-invasively in chronic hypoxic murine models
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