Table Of ContentHandbook of Tissue Optical Clearing
Handbook of Tissue Optical Clearing
New Prospects in Optical Imaging
Edited by
Valery V. Tuchin, Dan Zhu, and Elina A. Genina
First edition published 2022
by CRC Press
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Library of Congress Cataloging-in-Publication Data
Names: Tuchin, V. V. (Valeriĭ Viktorovich), editor. | Dan, Zhu, editor. |
Genina, Elina A., editor.
Title: Handbook of tissue optical clearing : new prospects in optical
imaging / edited by Valery Tuchin, Zhu Dan and Elina A. Genina.
Description: First edition. | Boca Raton : CRC Press, 2022. | Includes
bibliographical references and index.
Identifiers: LCCN 2021023380 | ISBN 9780367895099 (hardback) | ISBN
9781032118697 (paperback) | ISBN 9781003025252 (ebook)
Subjects: LCSH: Tissues--Imaging. | Tissues--Optical properties. | Imaging
systems in medicine.
Classification: LCC QP88 .H32 2022 | DDC 612.8/4--dc23
LC record available at https://lccn.loc.gov/2021023380
ISBN: 978-0-367-89509-9 (hbk)
ISBN: 978-1-032-11869-7 (pbk)
ISBN: 978-1-003-02525-2 (ebk)
DOI: 10.1201/9781003025252
Typeset in Times
by Deanta Global Publishing Services, Chennai, India
Contents
Preface ............................................................................................................................................................................................ix
Acknowledgments .........................................................................................................................................................................xiii
Editors ............................................................................................................................................................................................xv
Contributors .................................................................................................................................................................................xvii
Part I Basic principles of tissue optical clearing
1. Tissue optical clearing mechanisms .....................................................................................................................................3
Tingting Yu, Dan Zhu, Luís Oliveira, Elina A. Genina, Alexey N. Bashkatov, and Valery V. Tuchin
2. Tissue optical clearing for Mueller matrix microscopy ...................................................................................................31
Nan Zeng, Honghui He, Valery V. Tuchin, and Hui Ma
3. Traditional and innovative optical clearing agents...........................................................................................................67
Elina A. Genina, Vadim D. Genin, Jingtan Zhu, Alexey N. Bashkatov, Dan Zhu, and Valery V. Tuchin
4. Chemical enhancers for improving tissue optical clearing efficacy ................................................................................93
Dan Zhu, Yanmei Liang, Xingde Li, and Valery V. Tuchin
5. Human skin autofluorescence and optical clearing ........................................................................................................109
Walter Blondel, Marine Amouroux, Sergey M. Zaytsev, Elina A. Genina, Victor Colas, Christian Daul,
Alexander B. Pravdin, and Valery V. Tuchin
6. Molecular modeling of post-diffusion phase of optical clearing of biological tissues .................................................127
Kirill V. Berezin, Konstantin N. Dvoretskiy, Maria L. Chernavina, Anatoly M. Likhter, and Valery V. Tuchin
7. Refractive index measurements of tissue and blood components and OCAs in a wide spectral range .....................141
Ekaterina N. Lazareva, Luís Oliveira, Irina Yu. Yanina, Nikita V. Chernomyrdin, Guzel R. Musina,
Daria K. Tuchina, Alexey N. Bashkatov, Kirill I. Zaytsev, and Valery V. Tuchin
8. Water migration at skin optical clearing ..........................................................................................................................167
Anton Yu. Sdobnov, Johannes Schleusener, Jürgen Lademann, Valery V. Tuchin, and Maxim E. Darvin
9. Optical and mechanical properties of cartilage during optical clearing .....................................................................185
Yulia M. Alexandrovskaya, Olga I. Baum, Vladimir Yu. Zaitsev, Alexander A. Sovetsky, Alexander L. Matveyev,
Lev A. Matveev, Kirill V. Larin, Emil N. Sobol, and Valery V. Tuchin
10. Compression optical clearing ............................................................................................................................................199
Olga A. Zyuryukina and Yury P. Sinichkin
Part II Tissue optical clearing method for biology (3D imaging)
11. Optical clearing for multiscale tissues and the quantitative evaluation of clearing methods in mouse organs .............221
Tingting Yu, Jianyi Xu, and Dan Zhu
12. Ultrafast aqueous clearing methods for 3D imaging ......................................................................................................239
Tingting Yu, Jingtan Zhu, and Dan Zhu
13. Challenges and opportunities in hydrophilic tissue clearing methods .........................................................................257
Etsuo A. Susaki and Hiroki R. Ueda
v
vi Contents
14. Combination of tissue optical clearing and 3D fluorescence microscopy for high-throughput imaging
of entire organs and organisms ........................................................................................................................................277
Peng Fei and Chunyu Fang
15. Endogenous fluorescence preservation from solvent-based optical clearing ...............................................................297
Tingting Yu, Yisong Qi, and Dan Zhu
16. Progress in ex situ tissue optical clearing – shifting immuno-oncology to the third dimension .................................315
Paweł Matryba, Leszek Kaczmarek, and Jakub Gołąb
Part III Towards in vivo tissue optical clearing
17. In vivo skin optical clearing methods for blood flow and cell imaging .........................................................................333
Dongyu Li, Wei Feng, Rui Shi, and Dan Zhu
18. In vivo skull optical clearing for imaging cortical neuron and vascular structure and function ...............................351
Dongyu Li, Yanjie Zhao, Chao Zhang, and Dan Zhu
19. In vivo skin optical clearing in humans ............................................................................................................................369
Elina A. Genina, Alexey N. Bashkatov, Vladimir P. Zharov, and Valery V. Tuchin
20. Optical clearing of blood and tissues using blood components .....................................................................................383
Olga S. Zhernovaya, Elina A. Genina, Valery V. Tuchin, and Alexey N. Bashkatov
21. Blood and lymph flow imaging at optical clearing ..........................................................................................................393
Polina A. Dyachenko (Timoshina), Arkady S. Abdurashitov, Oxana V. Semyachkina-Glushkovskaya,
and Valery V. Tuchin
Part IV Combination of tissue optical clearing and optical
imaging/spectroscopy for diagnostics
22. Optical clearing aided photoacoustic imaging in vivo .....................................................................................................411
Yong Zhou and Lihong V. Wang
23. Enhancement of contrast in photoacoustic – fluorescence tomography and cytometry using
optical clearing and contrast agents ..................................................................................................................................419
Julijana Cvjetinovic, Daniil V. Nozdriukhin, Maksim Mokrousov, Alexander Novikov, Marina V. Novoselova,
Valery V. Tuchin, and Dmitry A. Gorin
24. Tissue optical clearing in the terahertz range .................................................................................................................445
Olga A. Smolyanskaya, Kirill I. Zaytsev, Irina N. Dolganova, Guzel R. Musina, Daria K. Tuchina,
Maxim M. Nazarov, Alexander P. Shkurinov, and Valery V. Tuchin
25. Magnetic resonance imaging study of diamagnetic and paramagnetic agents for optical clearing
of tumor-specific fluorescent signal in vivo ......................................................................................................................459
Alexei A. Bogdanov Jr., Natalia I. Kazachkina, Victoria V. Zherdeva, Irina G. Meerovich, Daria K. Tuchina,
Ilya D. Solovyev, Alexander P. Savitsky, and Valery V. Tuchin
26. Use of optical clearing and index matching agents to enhance the imaging of caries, lesions,
and internal structures in teeth using optical coherence tomography and SWIR imaging .......................................471
Daniel Fried
27. Optical clearing of adipose tissue .....................................................................................................................................487
Irina Yu. Yanina, Yohei Tanikawa, Daria K. Tuchina, Polina A. Dyachenko (Timoshina), Yasunobu Iga,
Shinichi Takimoto, Elina A. Genina, Alexey N. Bashkatov, Georgy S. Terentyuk, Nikita A. Navolokin,
Alla B. Bucharskaya, Galina N. Maslyakova, and Valery V. Tuchin
Contents vii
28. Diabetes mellitus-induced alterations of tissue optical properties, optical clearing efficiency,
and molecular diffusivity ....................................................................................................................................................517
Daria K. Tuchina and Valery V. Tuchin
29. Tissue optical clearing for in vivo detection and imaging diabetes induced changes in cells,
vascular structure, and function ......................................................................................................................................539
Dongyu Li, Wei Feng, Rui Shi, Valery V. Tuchin, and Dan Zhu
30. Light operation on cortex through optical clearing skull window ................................................................................557
Dongyu Li, Chao Zhang, Oxana Glushkovskaya, Yanjie Zhao, and Dan Zhu
31. The role of optical clearing to enhance the applications of in vivo OCT and photodynamic therapy:
Towards PDT of pigmented melanomas and beyond .....................................................................................................569
Layla Pires, Michelle Barreto Requena, Valentin Demidov, Ana Gabriela Salvio,
I. Alex Vitkin, Brian C. Wilson, and Cristina Kurachi
32. Combination of tissue optical clearing and OCT for tumor diagnosis via permeability
coefficient measurements ...................................................................................................................................................577
Qingliang Zhao
33. Optical clearing for cancer diagnostics and monitoring ................................................................................................597
Luís M. Oliveira and Valery V. Tuchin
34. Contrast enhancement and tissue differentiation in optical coherence tomography
with mechanical compression ...........................................................................................................................................607
Pavel D. Agrba and Mikhail Yu. Kirillin
35. Measurement of the dermal beta-carotene in the context of multimodal optical clearing .........................................619
Mohammad Ali Ansari and Valery V. Tuchin
36. Optical clearing and molecular diffusivity of hard and soft oral tissues .....................................................................629
Alexey A. Selifonov and Valery V. Tuchin
37. Optical clearing and Raman spectroscopy: In vivo applications ..................................................................................647
Qingyu Lin, Ekaterina N. Lazareva, Vyacheslav I. Kochubey, Yixiang Duan, and Valery V. Tuchin
Index ............................................................................................................................................................................................655
Preface
As one of the fastest-growing fields in the life sciences, bio- Journal of Innovative Optical Health and Science in 2010 [8]
medical photonics connects research in physics, optics, and were organized. In two monographs, the problem of optical
electrical engineering coupled with medical or biological clearing is discussed in general with many practical examples
applications, allowing structural and functional analysis of tis- [9] (see Chapter 9) as well as in terms of its specific aspects,
sues and cells with resolution and contrast unattainable by any with a focus on measuring and controlling the refractive
other method. The major challenges of many biophotonics tech- index of individual tissue components [10]. In addition, more
niques are associated with the need to enhance imaging reso- and more papers were published in journals, even top-level
lution even further to the subcellular level as well as translate journals. Therefore, this book, Handbook of Tissue Optical
them for in vivo studies. In the last few decades, huge advances Clearing: New Prospects in Optical Imaging, which differs
have been made in optical methods and optical molecular from the published books, is conceived, discussed, and written
probes, paving the way towards real molecular imaging within with chapter contributions from the subject area specialists.
cells, as well as deep-tissue imaging. However, the inherent With the development of advanced optical imaging technolo-
opacity of most biological tissues, which contain various cellu- gies, numerous tissue optical clearing methods have sprung
lar and extracellular structures with different refractive indices up in recent years, especially for in vitro tissue blocks, organs,
as well as kinds of pigments, limits the penetration of light and and bodies, and even human tissue; and also in vivo skin,
causes blurring of the images. Both the imaging resolution and skull, and sclera. The combination of tissue optical clearing
contrast decrease as light propagates deeper into the tissue and methods and advanced optical imaging techniques has been
travels through different components. To perform deeper tis- widely applied in different fields, such as neuroscience, anat-
sue imaging, great efforts have been made in terms of innova- omy, development, regeneration, and other physiological and
tion in advanced optical imaging techniques and development pathological processes, boosting our understanding of many
in optical molecular. Alternatively, reducing the scattering and biological events and offering novel insights into fundamental
absorption of tissues probes can also significantly enhance the questions in many discoveries, and it is also expected to play
optical imaging of deep tissue. For example, Richard White an essential role in clinical diagnosis applications.
and co-authors used careful breeding techniques to create a This book is a self-contained introduction to tissue optical
transparent adult zebrafish in 2008, which has been applied to clearing, aiming to introduce the up-to-date developments in
the study of cancer pathology and development in real time, tissue optical clearing in both methodology and application to
but this technique is unsuitable for studies in humans or other help readers understand the recent achievements of this tech-
animals [1]. nique systematically and comprehensively. This book covers
At the beginning of the 20th century, Werner Spalteholz four parts consisting of 37 chapters, including basic principles
used organic solvents to make large organs, such as the heart, of tissue optical clearing (Part I), in vitro tissue optical clear-
transparent [2], pushing forward unprecedented advances in ing method for 3D imaging (Part II), in vivo tissue optical
the field of anatomy. This was the first tissue clearing method clearing methods (Part III), and the combination of tissue opti-
of traceability. However, the severe damage it caused to outer cal clearing and optical imaging/spectroscopy for diagnostics
tissue made it useful only for clearing very large samples. Since (Part IV).
then, some improved or modified Spalteholz techniques have This book starts from the basic principles of tissue opti-
partially succeeded with the preservation of the histology [3]. cal clearing, aiming to elucidate optical clearing mechanisms
Although tissue clearing technology dates back to a century from physical, chemical, molecular, and even mechanical
ago, the formal concept of “tissue optical clearing” was pro- aspects. Part I includes an overview of the fundamental physi-
posed by Valery V. Tuchin and coauthors in 1996 [4]. It provides cal principles of current tissue optical clearing via various
an innovative way to perform deep-tissue imaging by reducing chemical strategies, such as dissociation of collagen, dehy-
the light attenuation and enhancing light penetration into the dration, delipidation, decalcification, and hyperhydration, to
tissues. After almost 10 years of development, the book Optical reduce scattering as well as decolorization to reduce absorp-
Clearing of Tissue and Blood (SPIE Press) was first published tion. Some recent progress on Mueller matrix imaging applied
in 2005 [5]; it described the optical clearing method based on in recording the optical clearing process is also reviewed.
reversible reduction of tissue scattering due to refractive index Then, the traditional and innovative optical clearing agents
matching of scatterers and ground matter and overviewed the and the chemical enhancers for improving optical clearing
basic principles, recent results, advantages, limitations, and efficacy are introduced, followed by a discussion of the impact
future of the optical immersion method applied to clearing of of optical clearing agents on human skin autofluorescence.
the naturally turbid biological tissues and blood. Then the molecular mechanism of the post-diffusion stage of
In the last decades, tissue optical clearing techniques devel- tissue optical clearing is explained by presenting the modeling
oped rapidly. Three special issues, two for the Journal of results of the interaction of optical clearing agents with colla-
Biomedical Optics in 2008 [6] and 2016 [7], and one for the gen by classical molecular dynamics, molecular docking, and
ix
