Physical and chemical mechanisms of tissue optical clearing

Yu, Tingting; Zhu, Jingtan; Li, Dongyu; Zhu, Dan

doi:10.1016/j.isci.2021.102178

Cited by 78 publications

(72 citation statements)

References 128 publications

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“…Many reviews have discussed tissue-clearing methods, with either an in-depth focus on the physicochemical principles (Richardson and Lichtman, 2015;Tainaka et al, 2016;Yu et al, 2021) or specific applications in neuroscience (Escalante et al, 2020;Ueda et al, 2020a,b;Vigouroux et al, 2017), cardiovascular development (Kolesová et al, 2021), pancreas (Campbell-Thompson and Tang, 2021) or biomedical applications (Almagro et al, 2021;Feuchtinger et al, 2016;Gómez-Gaviro et al, 2020). General guides are also available to help select clearing methods or imaging strategies (Ariel, 2017(Ariel, , 2018Molbay et al, 2021;Weiss et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Tissue clearing and 3D imaging in developmental biology

Vieites‐Prado

Renier

2021

Development

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Tissue clearing increases the transparency of late developmental stages and enables deep imaging in fixed organisms. Successful implementation of these methodologies requires a good grasp of sample processing, imaging and the possibilities offered by image analysis. In this Primer, we highlight how tissue clearing can revolutionize the histological analysis of developmental processes and we advise on how to implement effective clearing protocols, imaging strategies and analysis methods for developmental biology.

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Section: Introductionmentioning

confidence: 99%

Tissue clearing and 3D imaging in developmental biology

Vieites‐Prado

Renier

2021

Development

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“…This step is called refractive index (RI) matching because the RI is a preferred indicator of optical properties. However, this process is relatively complex physicochemically and not necessarily limited to RI homogenization, as dispersion of the fibrous structures of the extracellular matrix and the affinity (infiltration) of compounds into living tissues may also have significant effects (Ueda et al, 2020a;Yu et al, 2021). RI matching can also be combined with other processes to remove light-scattering and light-absorbing substances from the biological tissue, such as lipids (delipidation), the bone matrix (decalcification), and pigments (decolorization or bleaching).…”

Section: Brief Overview Of Modern Tissue Clearing Technologiesmentioning

confidence: 99%

Perspective: Extending the Utility of Three-Dimensional Organoids by Tissue Clearing Technologies

Susaki

Takasato

2021

Front. Cell Dev. Biol.

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An organoid, a self-organizing organ-like tissue developed from stem cells, can exhibit a miniaturized three-dimensional (3D) structure and part of the physiological functions of the original organ. Due to the reproducibility of tissue complexity and ease of handling, organoids have replaced real organs and animals for a variety of uses, such as investigations of the mechanisms of organogenesis and disease onset, and screening of drug effects and/or toxicity. The recent advent of tissue clearing and 3D imaging techniques have great potential contributions to organoid studies by allowing the collection and analysis of 3D images of whole organoids with a reasonable throughput and thus can expand the means of examining the 3D architecture, cellular components, and variability among organoids. Genetic and histological cell-labeling methods, together with organoid clearing, also allow visualization of critical structures and cellular components within organoids. The collected 3D data may enable image analysis to quantitatively assess structures within organoids and sensitively/effectively detect abnormalities caused by perturbations. These capabilities of tissue/organoid clearing and 3D imaging techniques not only extend the utility of organoids in basic biology but can also be applied for quality control of clinical organoid production and large-scale drug screening.

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“…Irrespective of the TOC method used, this set of techniques aims at turning opaque samples into translucent, light-permitting ones (Figure 2) [24][25][26]. The resulting transparency enables imaging deep into the tissue which is further advanced when combined with SPIM technology to look at the larger focal areas with reduced photobleaching ("planeby-plane" imaging), then with confocal microscopy ("point-by-point" imaging).…”

Section: Tissue Optical Clearing (Toc) Techniquesmentioning

confidence: 99%

“…In an application-based manner, crucial for proper combination with the specific SRM approach, chemical and physical mechanisms of TOC play a decisive role. These include decolorization, delipidation, dehydration or hyperhydration, decalcification and dissociation of collagen fibers and have been recently broadly discussed by the Zhu group [25] and us [19]. Briefly, decolorization (of heme, melanin, chlorophyll and lipofuscin) and delipidation enhance light penetration through the sample, while delipidation additionally acts as a permeabilization buffer that aids in the penetration of probes.…”

Section: Tissue Optical Clearing (Toc) Techniquesmentioning

confidence: 99%

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Can Developments in Tissue Optical Clearing Aid Super-Resolution Microscopy Imaging?

Matryba

Łukasiewicz

Pawłowska

et al. 2021

IJMS

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The rapid development of super-resolution microscopy (SRM) techniques opens new avenues to examine cell and tissue details at a nanometer scale. Due to compatibility with specific labelling approaches, in vivo imaging and the relative ease of sample preparation, SRM appears to be a valuable alternative to laborious electron microscopy techniques. SRM, however, is not free from drawbacks, with the rapid quenching of the fluorescence signal, sensitivity to spherical aberrations and light scattering that typically limits imaging depth up to few micrometers being the most pronounced ones. Recently presented and robustly optimized sets of tissue optical clearing (TOC) techniques turn biological specimens transparent, which greatly increases the tissue thickness that is available for imaging without loss of resolution. Hence, SRM and TOC are naturally synergistic techniques, and a proper combination of these might promptly reveal the three-dimensional structure of entire organs with nanometer resolution. As such, an effort to introduce large-scale volumetric SRM has already started; in this review, we discuss TOC approaches that might be favorable during the preparation of SRM samples. Thus, special emphasis is put on TOC methods that enhance the preservation of fluorescence intensity, offer the homogenous distribution of molecular probes, and vastly decrease spherical aberrations. Finally, we review examples of studies in which both SRM and TOC were successfully applied to study biological systems.

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Physical and chemical mechanisms of tissue optical clearing

Cited by 78 publications

References 128 publications

Tissue clearing and 3D imaging in developmental biology

Tissue clearing and 3D imaging in developmental biology

Perspective: Extending the Utility of Three-Dimensional Organoids by Tissue Clearing Technologies

Can Developments in Tissue Optical Clearing Aid Super-Resolution Microscopy Imaging?

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