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      Fluorescence Molecular Tomography: Principles and Potential for Pharmaceutical Research

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          Abstract

          Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue's optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development.

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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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            New strategies for fluorescent probe design in medical diagnostic imaging.

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              Optical tomography in medical imaging

              S Arridge (1999)
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                Pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                June 2011
                26 April 2011
                : 3
                : 2
                : 229-274
                Affiliations
                [1 ]Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
                [2 ]Institute of Electronic Structure and Laser - FORTH, Vassilika Vouton, 71110 Heraklion, Greece
                [3 ]Institute of Pharmacology and Toxicology, University Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mail: jripoll@ 123456iesl.forth.gr (J.R.); Tel.: +30 2810 391922 (J.R.); Fax: +30 2810 391305 (J.R.); E-Mail: rudin@ 123456biomed.ee.ethz.ch (M.R.); Tel.: +41 44 6337604 (M.R.); Fax: +41 44 6331187 (M.R.).
                Article
                pharmaceutics-03-00229
                10.3390/pharmaceutics3020229
                3864234
                24310495
                f10d01b1-44c0-431a-b6c9-0d185f0bc39a
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 06 February 2011
                : 07 April 2011
                : 15 April 2011
                Categories
                Review

                fluorescence molecular tomography,biomedical imaging,optical tomography,fluorescence,hybrid imaging

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