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      Multispectral optoacoustic tomography of myocardial infarction

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          Highlights

          ► Multispectral optoacoustics enables in vivo preclinical imaging of heart infarct. ► The spatial resolution is superior to previous deep-tissue optical techniques. ► Molecular contrast is provided by an exogenous inflammation-targeted agent. ► Endogenous contrast provides an anatomical reference for the molecular signal.

          Abstract

          Objectives

          To investigate the feasibility of a high resolution optical imaging strategy for myocardial infarction.

          Background

          Near-infrared approaches to imaging cardiovascular disease enable visualization of disease-associated biological processes in vivo. However, even at the scale of small animals, the strong scattering of light prevents high resolution imaging after the first 1–2 mm of tissue, leading to degraded signal localization.

          Methods

          Multispectral optoacoustic tomography (MSOT) was used to non-invasively image myocardial infarction (MI) in a murine model of coronary artery ligation at resolutions not possible with current deep-tissue optical imaging methods. Post-MI imaging was based on resolving the spectral absorption signature of a dendritic polyglycerol sulfate-based (dPGS) near-infrared imaging agent targeted to P- and L-selectin.

          Results

          In vivo imaging succeeded in detection of the agent in the injured myocardium after intravenous injection. The high anatomic resolution (<200 μm) achieved by the described method allowed signals originating in the infarcted heart to be distinguished from uptake in adjacent regions. Histological analysis found dPGS signal in infarcted areas, originating from leukocytes and endothelial cells.

          Conclusions

          MSOT imaging of myocardial infarction provides non-invasive visualization of optical contrast with a high spatial resolution that is not degraded by the scattering of light.

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          Most cited references23

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          Going deeper than microscopy: the optical imaging frontier in biology.

          Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.
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            The inflammatory response in myocardial infarction.

            One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
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              Molecular imaging by means of multispectral optoacoustic tomography (MSOT).

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                Author and article information

                Contributors
                Journal
                Photoacoustics
                Photoacoustics
                Photoacoustics
                Elsevier
                2213-5979
                10 December 2012
                March 2013
                10 December 2012
                : 1
                : 1
                : 3-8
                Affiliations
                [1 ]Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
                [2 ]Chair for Biological Imaging, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany
                [3 ]Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany
                [4 ]Research Unit Analytical Pathology - Institute for Pathology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
                [5 ]mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany
                [6 ]Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
                Author notes
                [* ]Corresponding author at: Technische Universität München, Lehrstuhl für Biologische Bildgebung, Ismaninger Str. 22, 81675 München, Germany. Tel.: +49 89 3187 3852 (assistant); fax: +49 89 3187 3008. adrian.taruttis@ 123456mytum.de
                Article
                S2213-5979(12)00003-1
                10.1016/j.pacs.2012.11.001
                4182822
                25327410
                8059f86c-950c-4a6a-b341-71c91ef784a6
                © 2012 Elsevier GmbH.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 26 July 2012
                : 14 November 2012
                : 14 November 2012
                Categories
                Research Article

                myocardial infarction,optical imaging,optoacoustic imaging

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