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      Non-invasive determination of murine placental and foetal functional parameters with multispectral optoacoustic tomography

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          Abstract

          Despite the importance of placental function in embryonic development, it remains poorly understood and challenging to characterize, primarily due to the lack of non-invasive imaging tools capable of monitoring placental and foetal oxygenation and perfusion parameters during pregnancy. We developed an optoacoustic tomography approach for real-time imaging through entire ~4 cm cross-sections of pregnant mice. Functional changes in both maternal and embryo regions were studied at different gestation days when subjected to an oxygen breathing challenge and perfusion with indocyanine green. Structural phenotyping of the cross-sectional scans highlighted different internal organs, whereas multi-wavelength acquisitions enabled non-invasive label-free spectroscopic assessment of blood-oxygenation parameters in foeto-placental regions, rendering a strong correlation with the amount of oxygen administered. Likewise, the placental function in protecting the embryo from extrinsically administered agents was substantiated. The proposed methodology may potentially further serve as a probing mechanism to appraise embryo development during pregnancy in the clinical setting.

          Optoacoustic imaging: Monitoring placental and fetal health

          A non-invasive imaging tool that reveals blood oxygen levels and perfusion in mice placentas and fetuses has potential applications for monitoring preeclampsia and other pregnancy disorders. Optoacoustic (OA) imaging involves sending laser pulses into biological tissue. The light absorption results in emission of ultrasonic waves, which are detected and used to build up images representing physiological factors such as oxygen levels. Daniel Razansky at the University of Zurich and ETH Zurich, Switzerland, and co-workers used OA imaging to non-invasively monitor placental and fetal function in pregnant mice. The team administered near-infrared contrast agent and alternate doses of 20 and 100% oxygen to the mice via breathing apparatus and monitored the resulting blood oxygenation and perfusion parameters. The images provided unprecedented detail showing how the placenta protects the embryo from excessive oxygen and extrinsically administered agents.

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          Most cited references40

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          Single-impulse Panoramic Photoacoustic Computed Tomography of Small-animal Whole-body Dynamics at High Spatiotemporal Resolution

          Imaging of small animals has played an indispensable role in preclinical research by providing high dimensional physiological, pathological, and phenotypic insights with clinical relevance. Yet pure optical imaging suffers from either shallow penetration (up to ~1–2 mm) or a poor depth-to-resolution ratio (~1/3), and non-optical techniques for whole-body imaging of small animals lack either spatiotemporal resolution or functional contrast. Here, we demonstrate that standalone single-impulse photoacoustic computed tomography (SIP-PACT) mitigates these limitations by combining high spatiotemporal resolution (125-µm in-plane resolution, 50 µs / frame data acquisition and 50-Hz frame rate), deep penetration (48-mm cross-sectional width in vivo), anatomical, dynamical and functional contrasts, and full-view fidelity. By using SIP-PACT, we imaged in vivo whole-body dynamics of small animals in real time and obtained clear sub-organ anatomical and functional details. We tracked unlabeled circulating melanoma cells and imaged the vasculature and functional connectivity of whole rat brains. SIP-PACT holds great potential for both pre-clinical imaging and clinical translation.
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            Advanced optoacoustic methods for multiscale imaging of in vivo dynamics

            Visualization of dynamic functional and molecular events in an unperturbed in vivo environment is essential for understanding the complex biology of living organisms and of disease state and progression. To this end, optoacoustic (photoacoustic) sensing and imaging have demonstrated the exclusive capacity to maintain excellent optical contrast and high resolution in deep-tissue observations, far beyond the penetration limits of modern microscopy. Yet, the time domain is paramount for the observation and study of complex biological interactions that may be invisible in single snapshots of living systems. This review focuses on the recent advances in optoacoustic imaging assisted by smart molecular labeling and dynamic contrast enhancement approaches that enable new types of multiscale dynamic observations not attainable with other bio-imaging modalities. A wealth of investigated new research topics and clinical applications is further discussed, including imaging of large-scale brain activity patterns, volumetric visualization of moving organs and contrast agent kinetics, molecular imaging using targeted and genetically expressed labels, as well as three-dimensional handheld diagnostics of human subjects.
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              Indocyanine green angiography: a perspective on use in the clinical setting.

              To review the history of indocyanine green (ICG) angiography and to present a personal perspective on its use in the clinical setting today. Perspective with literature review and opinions based on personal experience. To acquire views from international retinal physicians experienced with the technique on uses in their facilities and to compare them to the author's personal standards. The author and contributing retinal physicians had surprisingly similar views for most, but not all, applications for ICG angiography use in the clinical setting. ICG angiography is recommended for a few highly selective chorioretinal disorders, including certain forms of neovascularization in age-related macular degeneration, other neovascular maculopathies, chronic central serous chorioretinopathy, choroidal hemangiomas, and posterior uveitis. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                daniel.razansky@uzh.ch
                Journal
                Light Sci Appl
                Light Sci Appl
                Light, Science & Applications
                Nature Publishing Group UK (London )
                2095-5545
                2047-7538
                14 August 2019
                14 August 2019
                2019
                : 8
                : 71
                Affiliations
                [1 ]ISNI 0000000123222966, GRID grid.6936.a, Faculty of Medicine, , Technical University Munich, ; Munich, Germany
                [2 ]ISNI 0000 0004 0483 2525, GRID grid.4567.0, Institute for Biological and Medical Imaging, , Helmholtz Center Munich, ; Neuherberg, Germany
                [3 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Faculty of Medicine and Institute of Pharmacology and Toxicology, , University of Zurich, ; Zurich, Switzerland
                [4 ]ISNI 0000 0001 2156 2780, GRID grid.5801.c, Institute for Biomedical Engineering and Department of Information Technology and Electrical Engineering, ETH Zurich, ; Zurich, Switzerland
                [5 ]Present Address: Kausik Basak, Institute of Advanced Studies and Research, JIS University, Kolkata, West Bengal India
                Article
                181
                10.1038/s41377-019-0181-7
                6804938
                31666944
                d7b69aae-fbdd-40b7-b4a5-fa77f36a6143
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 February 2019
                : 27 June 2019
                : 17 July 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);
                Award ID: ERC-2015-CoG-682379
                Award Recipient :
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                © The Author(s) 2019

                photoacoustics,biophotonics,imaging and sensing
                photoacoustics, biophotonics, imaging and sensing

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