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Review
. 2022 May;157(5):497-511.
doi: 10.1007/s00418-022-02081-5. Epub 2022 Mar 2.

Optical tissue clearing associated with 3D imaging: application in preclinical and clinical studies

Cinzia Brenna  1   2 , Carolina Simioni  3   4 , Gabriele Varano  1 , Ilaria Conti  1 , Eva Costanzi  1 , Mattia Melloni  1 , Luca Maria Neri  5   6
Affiliations
Review

Optical tissue clearing associated with 3D imaging: application in preclinical and clinical studies

Cinzia Brenna et al. Histochem Cell Biol. 2022 May.

Abstract

Understanding the inner morphology of intact tissues is one of the most competitive challenges in modern biology. Since the beginning of the twentieth century, optical tissue clearing (OTC) has provided solutions for volumetric imaging, allowing the microscopic visualization of thick sections of tissue, organoids, up to whole organs and organisms (for example, mouse or rat). Recently, tissue clearing has also been introduced in clinical settings to achieve a more accurate diagnosis with the support of 3D imaging. This review aims to give an overview of the most recent developments in OTC and 3D imaging and to illustrate their role in the field of medical diagnosis, with a specific focus on clinical applications.

Keywords: 3D imaging; Clinical applications; Clinical diagnosis; OTC; Oncology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic workflow of the mode of action of confocal (a), two photon (b), and light sheet (c) microscopies. In diagrams (a) and (b), point A is represented in the focal plane, whereas point B is outside. Only the light sheet microscopy creates a light plane coincident with the focal plane, allowing the focus localization inside both of the points: https://biorender.com/
Fig. 2
Fig. 2
3D images of a wild-type mouse kidney, strain C57/Bl6, perfused with the cationic dye MHI148-PEI (patented according to the code WO/2018/100089), cleared by the optimized ECi protocol (see Huang et al. 2019), and imaged by CM (Leica TCS SP8, Leica Biosystem, Wetzlar, Germany), with HC PL APO 20/0.7 IMM oil CORR CS2 objective. The renal artery (a) and glomeruli (b) are shown for a total depth of 110 µm. The depth coding on the upper right part of both images displays the depth reached during the imaging. Specifically, the colored scale goes from the surface of the sample (0–50 μm, in blue–light blue), middle part (50–100 μm, in green) up to the deepest part of the region (100–150 μm, in yellow–red). Scale bars: 200 μm. The synthesis of the dye, mouse perfusion, sample harvesting, clearing, and imaging were conducted at the Zentrum für Medizinische Forschung (ZMF), Universitätsmedizin Mannheim (Germany)
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