<p>Biomedical photonics is currently one of the fastest growing fields, connecting research in physics, optics, and electrical engineering coupled with medical and biological applications. It allows for the structural and functional analysis of tissues and cells with resolution and contrast unattainable by any other methods. </p><p>However, the major challenges of many biophotonics techniques are associated with the need to enhance imaging resolution even further to the sub-cellular level as well as translate them for in vivo studies. The tissue optical clearing method uses immersion of tissues into optical clearing agents (OCAs) that reduces the scattering of tissue and makes tissue more transparent and this method has been successfully used ever since. </p><p>This book is a self-contained introduction to tissue optical clearing, including the basic principles and in vitro biological applications, from in vitro to in vivo tissue optical clearing methods, and combination of tissue optical clearing and various optical imaging for diagnosis. The chapters cover a wide range of issues related to the field of tissue optical clearing: mechanisms of tissue optical clearing in vitro and in vivo; traditional and innovative optical clearing agents; recent achievements in optical clearing of different tissues (including pathological tissues) and blood for optical imaging diagnosis and therapy. </p><p>This book provides a comprehensive account of the latest research and possibilities of utilising optical clearing as an instrument for improving the diagnostic effectiveness of modern optical diagnostic methods.</p><p>The book is addressed to biophysicist researchers, graduate students and postdocs of biomedical specialties, as well as biomedical engineers and physicians interested in the development and application of optical methods in medicine.</p><p>Key features:</p><ul> <p> </p> <li>The first collective reference to collate all known knowledge on this topic </li> <p> </p> <li>Edited by experts in the field with chapter contributions from subject area specialists</li> <p> </p> <li>Brings together the two main approaches in immersion optical clearing into one cohesive book</li> </ul> <p>Preface............................................................................................................................................................................................. ix</p><p>Acknowledgments..........................................................................................................................................................................xiii</p><p>Editors............................................................................................................................................................................................. xv</p><p>Contributors..................................................................................................................................................................................xvii</p><p>Part I Basic principles of tissue optical clearing</p><p>1. Tissue optical clearing mechanisms...................................................................................................................................... 3</p><p>Tingting Yu, Dan Zhu, Luís Oliveira, Elina A. Genina, Alexey N. Bashkatov, and Valery V. Tuchin</p><p>2. Tissue optical clearing for Mueller matrix microscopy.................................................................................................... 31</p><p>Nan Zeng, Honghui He, Valery V. Tuchin, and Hui Ma</p><p>3. Traditional and innovative optical clearing agents........................................................................................................... 67</p><p>Elina A. Genina, Vadim D. Genin, Jingtan Zhu, Alexey N. Bashkatov, Dan Zhu, and Valery V. Tuchin</p><p>4. Chemical enhancers for improving tissue optical clearing efficacy................................................................................. 93</p><p>Dan Zhu, Yanmei Liang, Xingde Li, and Valery V. Tuchin</p><p>5. Human skin autofluorescence and optical clearing......................................................................................................... 109</p><p>Walter Blondel, Marine Amouroux, Sergey M. Zaytsev, Elina A. Genina, Victor Colas, Christian Daul,</p><p>Alexander B. Pravdin, and Valery V. Tuchin</p><p>6. Molecular modeling of post-diffusion phase of optical clearing of biological tissues.................................................. 127</p><p>Kirill V. Berezin, Konstantin N. Dvoretskiy, Maria L. Chernavina, Anatoly M. Likhter, and Valery V. Tuchin</p><p>7. Refractive index measurements of tissue and blood components and OCAs in a wide spectral range......................141</p><p>Ekaterina N. Lazareva, Luís Oliveira, Irina Yu. Yanina, Nikita V. Chernomyrdin, Guzel R. Musina,</p><p>Daria K. Tuchina, Alexey N. Bashkatov, Kirill I. Zaytsev, and Valery V. Tuchin</p><p>8. Water migration at skin optical clearing...........................................................................................................................167</p><p>Anton Yu. Sdobnov, Johannes Schleusener, Jürgen Lademann, Valery V. Tuchin, and Maxim E. Darvin</p><p>9. Optical and mechanical properties of cartilage during optical clearing...................................................................... 185</p><p>Yulia M. Alexandrovskaya, Olga I. Baum, Vladimir Yu. Zaitsev, Alexander A. Sovetsky, Alexander L. Matveyev,</p><p>Lev A. Matveev, Kirill V. Larin, Emil N. Sobol, and Valery V. Tuchin</p><p>10. Compression optical clearing............................................................................................................................................. 199</p><p>Olga A. Zyuryukina and Yury P. Sinichkin</p><p>Part II Tissue optical clearing method for biology (3D imaging)</p><p>11. Optical clearing for multiscale tissues and the quantitative evaluation of clearing methods in mouse organs..............221</p><p>Tingting Yu, Jianyi Xu, and Dan Zhu</p><p>12. Ultrafast aqueous clearing methods for 3D imaging....................................................................................................... 239</p><p>Tingting Yu, Jingtan Zhu, and Dan Zhu</p><p>13. Challenges and opportunities in hydrophilic tissue clearing methods.......................................................................... 257</p><p>Etsuo A. Susaki and Hiroki R. Ueda</p><p>14. Combination of tissue optical clearing and 3D fluorescence microscopy for high-throughput imaging</p><p>of entire organs and organisms ......................................................................................................................................... 277</p><p>Peng Fei and Chunyu Fang</p><p>15. Endogenous fluorescence preservation from solvent-based optical clearing................................................................ 297</p><p>Tingting Yu, Yisong Qi, and Dan Zhu</p><p>16. Progress in ex situ tissue optical clearing – shifting immuno-oncology to the third dimension..................................315</p><p>Paweł Matryba, Leszek Kaczmarek, and Jakub Gołąb</p><p>Part III Towards <i>in vivo </i>tissue optical clearing</p><p>17. <i>In vivo </i>skin optical clearing methods for blood flow and cell imaging.......................................................................... 333</p><p>Dongyu Li, Wei Feng, Rui Shi, and Dan Zhu</p><p>18. <i>In vivo </i>skull optical clearing for imaging cortical neuron and vascular structure and function................................351</p><p>Dongyu Li, Yanjie Zhao, Chao Zhang, and Dan Zhu</p><p>19. <i>In vivo </i>skin optical clearing in humans............................................................................................................................. 369</p><p>Elina A. Genina, Alexey N. Bashkatov, Vladimir P. Zharov, and Valery V. Tuchin</p><p>20. Optical clearing of blood and tissues using blood components...................................................................................... 383</p><p>Olga S. Zhernovaya, Elina A. Genina, Valery V. Tuchin, and Alexey N. Bashkatov</p><p>21. Blood and lymph flow imaging at optical clearing........................................................................................................... 393</p><p>Polina A. Dyachenko (Timoshina), Arkady S. Abdurashitov, Oxana V. Semyachkina-Glushkovskaya,</p><p>and Valery V. Tuchin</p><p>Part IV Combination of tissue optical clearing and optical</p><p>imaging/spectroscopy for diagnostics</p><p>22. Optical clearing aided photoacoustic imaging <i>in vivo</i>......................................................................................................411</p><p>Yong Zhou and Lihong V. Wang</p><p>23. Enhancement of contrast in photoacoustic – fluorescence tomography and cytometry using</p><p>optical clearing and contrast agents...................................................................................................................................419</p><p>Julijana Cvjetinovic, Daniil V. Nozdriukhin, Maksim Mokrousov, Alexander Novikov, Marina V. Novoselova,</p><p>Valery V. Tuchin, and Dmitry A. Gorin</p><p>24. Tissue optical clearing in the terahertz range.................................................................................................................. 445</p><p>Olga A. Smolyanskaya, Kirill I. Zaytsev, Irina N. Dolganova, Guzel R. Musina, Daria K. Tuchina,</p><p>Maxim M. Nazarov, Alexander P. Shkurinov, and Valery V. Tuchin</p><p>25. Magnetic resonance imaging study of diamagnetic and paramagnetic agents for optical clearing</p><p>of tumor-specific fluorescent signal <i>in vivo</i>....................................................................................................................... 459</p><p>Alexei A. Bogdanov Jr., Natalia I. Kazachkina, Victoria V. Zherdeva, Irina G. Meerovich, Daria K. Tuchina,</p><p>Ilya D. Solovyev, Alexander P. Savitsky, and Valery V. Tuchin</p><p>26. Use of optical clearing and index matching agents to enhance the imaging of caries, lesions,</p><p>and internal structures in teeth using optical coherence tomography and SWIR imaging........................................ 471</p><p>Daniel Fried</p><p>27. Optical clearing of adipose tissue...................................................................................................................................... 487</p><p>Irina Yu. Yanina, Yohei Tanikawa, Daria K. Tuchina, Polina A. Dyachenko (Timoshina), Yasunobu Iga,</p><p>Shinichi Takimoto, Elina A. Genina, Alexey N. Bashkatov, Georgy S. Terentyuk, Nikita A. Navolokin,</p><p>Alla B. Bucharskaya, Galina N. Maslyakova, and Valery V. Tuchin</p><p>28. <i>Diabetes mellitus</i>-induced alterations of tissue optical properties, optical clearing efficiency,</p><p>and molecular diffusivity.....................................................................................................................................................517</p><p>Daria K. Tuchina and Valery V. Tuchin</p><p>29. Tissue optical clearing for in vivo detection and imaging diabetes induced changes in cells,</p><p>vascular structure, and function....................................................................................................................................... 539</p><p>Dongyu Li, Wei Feng, Rui Shi, Valery V. Tuchin, and Dan Zhu</p><p>30. Light operation on cortex through optical clearing skull window................................................................................. 557</p><p>Dongyu Li, Chao Zhang, Oxana Glushkovskaya, Yanjie Zhao, and Dan Zhu</p><p>31. The role of optical clearing to enhance the applications of <i>in vivo </i>OCT and photodynamic therapy:</p><p>Towards PDT of pigmented melanomas and beyond...................................................................................................... 569</p><p>Layla Pires, Michelle Barreto Requena, Valentin Demidov, Ana Gabriela Salvio,</p><p>I. Alex Vitkin, Brian C. Wilson, and Cristina Kurachi</p><p>32. Combination of tissue optical clearing and OCT for tumor diagnosis via permeability</p><p>coefficient measurements.................................................................................................................................................... 577</p><p>Qingliang Zhao</p><p>33. Optical clearing for cancer diagnostics and monitoring................................................................................................. 597</p><p>Luís M. Oliveira and Valery V. Tuchin</p><p>34. Contrast enhancement and tissue differentiation in optical coherence tomography</p><p>with mechanical compression............................................................................................................................................ 607</p><p>Pavel D. Agrba and Mikhail Yu. Kirillin</p><p>35. Measurement of the dermal beta-carotene in the context of multimodal optical clearing..........................................619</p><p>Mohammad Ali Ansari and Valery V. Tuchin</p><p>36. Optical clearing and molecular diffusivity of hard and soft oral tissues...................................................................... 629</p><p>Alexey A. Selifonov and Valery V. Tuchin</p><p>37. Optical clearing and Raman spectroscopy: <i>In vivo </i>applications................................................................................... 647</p><p>Qingyu Lin, Ekaterina N. Lazareva, Vyacheslav I. Kochubey, Yixiang Duan, and Valery V. Tuchin</p><p>Index............................................................................................................................................................................................. 655</p>