Handbook 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 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press 2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN © 2022 Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, LLC Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publica- tion and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. 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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