Volumetric optoacoustic tomography enables non-invasive in vivo characterization of impaired heart function in hypoxic conditions

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 noninvasive 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. Pulmonary hypertension (PH) is a disorder characterized by pulmonary vascular remodeling, right ventricular hypertrophy and increased pulmonary arterial pressure. PH has been associated with various disorders while, according to the recent WHO classification, it is regarded as a separate entity when associated with hypoxia or chronic diseases of the respiratory system 1. The latter include chronic obstructive pulmonary disease (COPD), interstitial lung diseases, sleep disordered breathing, but also chronic exposure to high altitude and some rare neonatal diseases 2,3. Murine models have been widely used to gain deeper insight into lung-heart interactions under chronic hypoxic conditions 4. The hypoxia-inducible factor (HIF) has been highly implicated in the development of PH 5 where several preclinical studies focus on the molecular mechanisms of HIF and its role in PH 6-9. However, there is a lack of direct functional studies of the heart in response to chronic hypoxia. Methods for assessing pulmonary and cardiac structural alterations in PH are usually limited to histopathological ex vivo analyses looking at right ventricular (RV) hypertrophy and pulmonary vasculature changes. RV catheterization is an invasive in vivo procedure to measure pressure differences as a surrogate parameter of increased pulmonary arterial pressure 10-13 .

Photoacoustic imaging in evaluating early intestinal ischemia injury and reperfusion injury in rat models

“…PAI is a non-invasive medical imaging method that combines the high contrast characteristics of pure optical imaging and the high penetration depth characteristics of pure ultrasound imaging and can also provide high resolution and high contrast tissue imaging. In our experiment, the mesenteric vessels in which we were interested were only a few millimeters below the surface of the irradiated tissue, and under proper illumination, the tissue depth could even be within 5 cm (depending on the illuminated organs) (27). When using a single acquisition mode, PAI can be considered instantaneous (usually completed in tens of milliseconds), which means no motion artifacts are generated (28,29).…”

Internal-Illumination Photoacoustic Tomography Enhanced by a Graded-Scattering Fiber Diffuser

“…We will try different image reconstruction and data processing methods to improve the image quality. For example, the PA imaging quality can be improved by using a matrix transducer probe as well as modelbased [63][64][65][66] or deep learning image reconstruction methods [67][68][69]. We have also explored our recently developed reconstruction approach based on the Wasserstein Generative Adversarial Network with gradient penalty (WGAN-GP) to improve the image quality (Supplementary Fig.…”

Photoacoustic Imaging in Evaluating Early Intestinal Ischemia and Reperfusion Injury with Rat Models

“…It combines the high contrast characteristics of pure optical imaging and the high penetration depth characteristics of pure ultrasound imaging, which can provide high resolution and high contrast tissue imaging. In our experiment, the mesenteric artery we interested in was only a few millimeters below the surface of the irradiated tissue, and under proper illumination, the tissue depth could even be within cm (depending on the irradiated organ) [25] . In addition, when using a single acquisition mode, PAI can be considered instantaneous (usually completed in tens of milliseconds), which means no motion artifacts are generated [26,27] .…”