In-vivo and ex-vivo optical clearing methods for biological tissues: review

Year: 2019

Authors: Costantini I., Cicchi R., Silvestri L., Vanzi F., Pavone F.S.

Autors Affiliation: National Institute of Optics, National Research Council, Via Nello Carrara 1, 50019 Sesto Fiorentino, Italy
European Laboratory for Non-linear Spectroscopy, University of Florence, Via Nello Carrara 1, 50019 Sesto Fiorentino, Italy
Department of Physics and Astronomy, University of Florence, Via Sansone 1, Sesto Fiorentino, 50019, Italy
Department of Biology, University of Florence, Via Madonna del Piano 6, Sesto Fiorentino, 50019, Italy

Abstract: Every optical imaging technique is limited in its penetration depth by scattering occurring in biological tissues. Possible solutions to overcome this problem consist of limiting the detrimental effects of scattering by reducing optical inhomogeneities within the sample. This can be achieved either by using physical methods (such as refractive index matching solutions) or by chemical methods (such as the removal of scatterers), based on tissue transformation protocols. This review provides an overview of the current state-of-the art methods used for both ex-vivo and in-vivo optical clearing of biological tissues. We start with a brief history of the development of the most widespread clearing methods across the new millennium, then we describe the working principles of both physical and chemical methods. Clearing methods are then reviewed, pointing the attention of the reader on both physical and chemical methods, classified based on the tissue size and type for each specific application. A small section is reserved for methods that have already found in-vivo applications at the research level. Finally, a detailed discussion highlighting both the most relevant results achieved and the new ongoing developments in this field is reported in the last part, together with future perspectives for the clearing methodology.


Volume: 10 (10)      Pages from: 5251  to: 5267

More Information: The research leading to these results has received funding from the European Union´s H2020 research and innovation program under grant agreements No. 785907 (Human Brain Project), 732111 (PICCOLO), and 654148 (Laserlab-Europe), and from the EU program H2020 EXCELLENT SCIENCE – European Research Council (ERC) under grant agreement ID n. 692943 (BrainBIT). This research has also been supported by the Italian Ministry for Education, University, and Research in the framework of the Flagship Project NanoMAX, by the Eurobioimaging Italian Nodes (ESFRI research infrastructure) – Advanced Light Microscopy Italian Node, by Italian Ministry of Health (RF-2013-02355240 and GR-2011-02349626), by Tuscany Region (Program PAR-FAS 2007-2013 – FAS Salute 2014, and Program BiophotonicsPlus-LITE), and by “Ente Cassa di Risparmio di Firenze” (private foundation).
KeyWords: enhanced transdermal delivery; stratum-corneum; high-resolution; human skin; coherence tomography; confocal images; microscopy; intact; contrast; agents; optical clearing methods; biological tissues
DOI: 10.1364/BOE.10.005251

Citations: 108
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