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Handbook of Optical Biomedical Diagnostics, Second Edition, Volume 2: Methods
Editor(s): Valery V. Tuchin
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Book Description

Since the publication of the first edition of the Handbook in 2002, optical methods for biomedical diagnostics have developed in many well-established directions, and new trends have also appeared. To encompass all current methods, the text has been updated and expanded into two volumes.

Volume 2: Methods begins by describing the basic principles and diagnostic applications of optical techniques based on detecting and processing the scattering, fluorescence, FT IR, and Raman spectroscopic signals from various tissues, with an emphasis on blood, epithelial tissues, and human skin. The second half of the volume discusses specific imaging technologies, such as Doppler, laser speckle, optical coherence tomography (OCT), and fluorescence and photoacoustic imaging.

Buy this volume and Volume 1: Light - Tissue Interaction as a set at a discount! PM264


Book Details

Date Published: 25 October 2016
Pages: 688
ISBN: 9781628419139
Volume: PM263

Table of Contents
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Table of Contents

Preface
List of Contributors

Part III: Scattering, Fluorescence, and Infrared Fourier Transform Spectroscopy of Tissues
Alexander V. Priezzhev and Juergen Lademann

1 Optical Study of RBC Aggregation in Whole Blood Samples and on the Single-Cell Level
Alexander V. Priezzhev, Kisung Lee, Nikolai N. Firsov, and Juergen Lademann
1.1 Introduction to the Microrheological Structure of Blood: Biophysical and Clinical Aspects
1.2 Importance of Quantitative Measurement of Red Blood Cell Aggregation and Deformability Parameters
1.3 Arrangement of a Couette Chamber-Based Laser Backscattering Aggregometer
     1.3.1 Measurement procedure
1.4 Kinetics of the Aggregation and Disaggregation Process
     1.4.1 Determination of the characteristic parameters of the aggregation and disaggregation process
1.5 Parameters Influencing the Aggregation and Disaggregation Measurements
     1.5.1 Effect of blood sample temperature
     1.5.2 Effect of blood sample oxygenation
     1.5.3 Effect of sedimentation
     1.5.4 Effect of hematocrit
1.6 Comparison of Aggregation and Disaggregation Measurements with Sedimentation Measurements
1.7 Laser Tweezers as a New Tool for Studying RBC Aggregation at the Single-Cell Level
     1.7.1 Laser tweezers operation principle and experimental arrangement
     1.7.2 Sample preparation and measurement procedure
1.8 Hemorheological Characterization of Various Diseases by Aggregation and Disaggregation Measurements of Blood Samples
References

2 Light Scattering Spectroscopy of Epithelial Tissues: Principles and Applications
Lev T. Perelman and Vadim Backman
2.1 Introduction
2.2 Microscopic Architecture of Mucosal Tissues
     2.2.1 Morphology of the cell
     2.2.2 Histology of mucosae
     2.2.3 Introduction to histopathology of early cancer and dysplasia
2.3 Principles of Light Scattering
     2.3.1 Rigorous solution of the direct scattering problem
     2.3.2 Approximate solutions of the scattering problem
     2.3.3 Numerical solutions of the scattering problem
2.4 Light Scattering by Cells and Subcellular Structures
2.5 Light Transport in Superficial Tissues
2.6 Detection of Cancer with Light Scattering Spectroscopy
     2.6.1 Diagnosis of early cancer and precancerous lesions with diffusely scattered light
     2.6.2 Diagnosis of early cancer and precancerous lesions with single-scattered light
     2.6.3 Imaging of early cancer and precancerous lesions with endoscopic polarized scanning spectroscopy instrument
2.7 Confocal Light Absorption and Scattering Spectroscopic Microscopy
References

3 Reflectance and Fluorescence Spectroscopy of Human Skin in vivo
Yuri P. Sinichkin, Nikiforos Kollias, George I. Zonios, Sergei R. Utz, and Valery V. Tuchin
3.1 Introduction
3.2 Human Skin Back-Reflectance and Autofluorescence Spectra Formation
     3.2.1 Diffuse reflectance spectrum
     3.2.2 Autofluorescence spectra
3.3 Simple Optical Models of Human Skin
     3.3.1 Simple skin model for reflectance analysis
     3.3.2 Simple skin model for autofluorescence analysis
3.4 Combined Reflectance and Fluorescence Spectroscopy Method for in vivo Skin Examination
     3.4.1 Correction of the internal absorption effect in fluorescence emission
     3.4.2 Determination of melanin and erythema indices
     3.4.3 Monitoring of hemoglobin oxygenation
3.5 Color Perception of Human Skin Back-Reflectance and Fluorescence Emission
     3.5.1 Color analysis of reflectance and fluorescence spectra
     3.5.2 Color imaging
3.6 Polarization Reflectance Spectroscopy
3.7 Polarization Imaging
3.8 Sunscreen Evaluation Using Reflectance and Fluorescence Spectroscopy
3.9 Control of Skin Optical Properties
     3.9.1 Introduction
     3.9.2 Skin compression and stretching
     3.9.3 Immersion optical clearing
          3.9.3.1 In vitro spectrophotometry
          3.9.3.2 In vivo spectral reflectance measurement
          3.9.3.3 Frequency-domain measurements
     3.9.4 Skin blood flow imaging
     3.9.5 OCT imaging
     3.9.6 Confocal microscopy
     3.9.7 Fluorescence and Raman signal detection
     3.9.8 The second harmonic generation
     3.9.9 Skin heating
     3.9.10 UV radiation
     3.9.11 Applications
     3.9.12 Conclusion
3.10 Conclusion
References

4 Infrared and Raman Spectroscopy of Human Skin in vivo
Gerald W. Lucassen, Peter J. Caspers, Gerwin J. Puppels, Maxim E. Darvin, and Juergen Lademann
4.1 Introduction: Basic Principles of IR and Raman Spectrosopy
4.2 Fourier-Transform Infrared Spectroscopy of Human Skin Stratum Corneum in vivo
     4.2.1 Experimental ATR-FTIR setup
     4.2.2 Human skin stratum corneum spectra and band assignments
     4.2.3 ATR-FTIR spectrum of water
          4.2.3.1 Water-bending mode and low-wavenumber region
     4.2.4 Stratum corneum hydration measurements
          4.2.4.1 OH stretch region
          4.2.4.2 Fit on water spectrum
     4.2.5 Band analysis of hydrated and normal skin
          4.2.5.1 Penetration depth of the IR beam
          4.2.5.2 Fits of the hydrated skin stratum corneum spectra
          4.2.5.3 Comparison with MF and IR absorbance ratio
4.3 Confocal Raman Microspectroscopy of Human Skin in vivo
     4.3.1 Setup for in vivo confocal Raman microspectroscopy
     4.3.2 Water and natural moisturizing factor in human skin epidermis
     4.3.3 Raman spectra of human skin constituents in vitro
     4.3.4 Profiling the water content and NMF content in human skin in vivo
4.4 Resonance Raman Spectroscopy of Cutaneous Carotenoids in vivo
     4.4.1 Properties and role of cutaneous carotenoids
     4.4.2 Setup for in vivo resonance Raman spectroscopy of carotenoids
     4.4.3 Selective detection of carotenoids in the human skin
     4.4.4 In vivo measurements of the influence of UV irradiation on the human skin
     4.4.5 In vivo measurements of the influence of IR irradiation on the human skin
     4.4.6 In vivo measurements of the influence of the VIS irradiation on the human skin
     4.4.7 Factors influencing the concentration of carotenoids in the human skin
     4.4.8 Distribution of carotenoids in the human skin
4.5 Conclusions
References

5 Fluorescence Technologies in Biomedical Diagnostics
Herbert Schneckenburger, Wolfgang S. L. Strauss, Karl Stock, and Rudolf Steiner
5.1 Introduction
     5.1.1 Fundamentals
     5.1.2 Potential diagram
     5.1.3 Jablonski diagram and kinetic rates
     5.1.4 Fluorescence anisotropy
5.2 Intrinsic and Extrinsic Fluorescence
     5.2.1 Intrinsic fluorophores
     5.2.2 Fluorescent markers
5.3 Spectroscopic, Microscopic, and Imaging Techniques
     5.3.1 Fluorescence spectroscopy
     5.3.2 Fluorescence microscopy
     5.3.3 Imaging techniques
5.4 Time-Resolved Fluorescence Spectroscopy and Imaging
     5.4.1 Time-correlated single photon counting
     5.4.2 Phase fluorometry
     5.4.3 Time-gated fluorescence spectroscopy
     5.4.4 Time-resolved fluorescence imaging
5.5 Total Internal Reflection Fluorescence Spectroscopy and Microscopy (TIRFS/TIRFM)
     5.5.1 Theory of TIRFS/TIRFM
     5.5.2 Technical setup
     5.5.3 Combination of TIRFS/TIRFM with innovative fluorescence microscopic techniques
     5.5.4 Application of TIRFS/TIRFM in cell biology
5.6 Energy Transfer Spectroscopy
     5.6.1 Basic mechanisms
     5.6.2 FRET applications
5.7 Wide-Field 3D Microscopy
     5.7.1 Structured illumination
     5.7.2 Light sheet fluorescence microscopy (LSFM)
5.8 Laser Scanning and Multiphoton Microscopy
     5.8.1 Introduction
     5.8.2 Performance of confocal laser scanning microscopes
     5.8.3 Applications of CLSM
     5.8.4 Multiphoton microscopy
     5.8.5 Super-resolution and single-molecule detection
5.9 Concluding Remarks
References

Part IV: Coherent-Domain Methods for Biological Flows and Tissue Ultrastructure Monitoring
J. David Briers and Sean J. Kirkpatrick

6 Laser Speckles, Doppler and Imaging Techniques for Blood and Lymph Flow Monitoring
Ivan V. Fedosov, Yoshihisa Aizu, Valery V. Tuchin, Naomichi Yokoi, Izumi Nishidate, Vladimir P. Zharov, and Ekaterina I. Galanzha
6.1.Introduction
6.2 Doppler and Speckle Techniques
     6.2.1 Laser Doppler technique
     6.2.2 Laser speckle technique
     6.2.3 Interrelation
6.3 Two-Wavelength Near-Infrared Speckle Imaging
     6.3.1 Optical system
     6.3.2 Frame-rate analysis of blood flow
     6.3.3 Blood flow measurements in humans
     6.3.4 Blood flow measurements in rats
     6.3.5 Simultaneous monitoring of blood flow and concentration
     6.3.6 Experiments on rats
6.4 Low-Coherence Speckle Interferometry
6.5 Quantitiave Characterization of Blood Flow Rate
     6.5.1 The use of laser Doppler anemometry for measurements of absolute blood flow velocity
     6.5.2 Intravital particle image velocimetry of capillary blood flow
6.6 Intravital Microscopy (IM) for Monitoring Blood and Lymph Flows
6.7 Intravital Transmission Digital Microscopy (ITDM)
6.8 Intravital Fluroescent Digital Microscopy (IFDM)
6.9 Optical Clearing
6.10 In vivo Flow Cytometry
6.11 In vivo Lymph Flow Cytometry (LFC)
6.12 Animal Models
6.13 Biomedical Applications
     6.13.1 Optical lymphography
          6.13.1.1 Indocyanine Green (ICG) Lymphography
          6.13.1.2 Integrated fluorescent angio- and lymphography
          6.13.1.3 Monitoring lymph flow profiles
     6.13.2 In vivo label-free imaging of lymphatic function
          6.13.2.1 Lymph flow
          6.13.2.2 Experimental lymphedema
          6.13.2.3 Nicotine intoxication
          6.13.2.4 Nitric oxide
          6.13.2.5 High-power laser�induced thermal effects on lymph vessels
     6.13.3 In vivo flow cytometry
          6.13.3.1 Label-free image flow cytometry
          6.13.3.2 Fluorescent image flow cytometry
References

7 Real-Time Imaging of Microstructure and Function Using Optical Coherence Tomography
Christine P. Hendon and Andrew M. Rollins
7.1 Introduction
7.2 Optical Coherence Tomography Principles
     7.2.1 Time-domain OCT
     7.2.2 Frequency-domain OCT
          7.2.2.1 Spectrometers
          7.2.2.2 Light sources
7.3 Functional Imaging
     7.3.1 Doppler OCT
     7.3.2 Polarization-sensitive OCT
7.4 Applications of OCT
     7.4.1 Opthamology
     7.4.2 Cardiology
     7.4.3 Oncology
7.5 Conclusions
References

8 Speckle Technologies for Monitoring and Imaging of Tissues and Tissue-Like Phantoms
Dmitry A. Zimnyakov, Olga V. Ushakova, David J. Briers, and Valery V. Tuchin
8.1 Introduction
8.2 Diffusing-Wave Spectroscopy (DWS) as a Tool for Tissue Structure and Cell Flow Monitoring
8.3 Laser Speckle Contrast Analysis (LASCA) for Measuring Blood Flow
     8.3.1 Statistical properties of laser speckle
     8.3.2 Time-varying speckle
     8.3.3 Full-field methods
     8.3.4 Single-exposure speckle photography
     8.3.5 Laser speckle contrast analysis (LASCA)
     8.3.6 The question of speckle size
     8.3.7 Theory
     8.3.8 Practical considerations
     8.3.9 Early applications of the LASCA technique
     8.3.10 Important developments of the basic LASCA technique
     8.3.11 Conclusions
8.4 Modification of Speckle Contrast Analysis to Improve Depth Resolution and to Characterize Scattering Properties of a Probed Medium
8.5 Various Modifications of Laser Speckle Contrast Imaging
8.6 Imaging Using Contrast Measurements of Partially Developed Speckles
8.7 Monitoring of Tissue Thermal Modification with a Bundle-Based Full-Field Speckle Analyzer
8.8 Summary
References

9 Optical Assessment of Tissue Mechanics
Sean J. Kirkpatrick, Donald D. Duncan, Brendan F. Kennedy, and David D. Sampson
9.1 Introduction
9.2 Introduction to Prior Edition
9.3 Tissue Mechanics and Medicine
     9.3.1 Dermatology
     9.3.2 Oncology
     9.3.3 Ophthalmology
     9.3.4 Cardiology
     9.3.5 Other application areas
9.4 Constitutive Relations in Biological Tissues
9.5 Laser Speckle Patterns Arising from Biological Tissues
     9.5.1 First-order statistics
     9.5.2 Second-order statistics
9.6 Elastography Measurements by Tracking Translating Laser Speckle: The Transform Method
     9.6.1 Potential error sources
     9.6.2 Applications of laser speckle elastography to hard and soft tissues
9.7 Alternative Processing Algorithms for Calculating Speckle Shift
     9.7.1 Nonparametric speckle shift estimators
     9.7.2 Parametric speckle shift estimators
     9.7.2.1 A minimum mean square error estimator
9.8 Expanding to Higher Dimensions
9.9 What is Really Measured in Laser Speckle-Tracking Elastography
9.10 In vivo Laser Speckle Tracking Optical Elastography
9.11 Performance Comparisons
9.12 Generalizations
9.13 Elastography of Tissues with Optical Coherence Tomography
     9.13.1 Variants of OCE
          9.13.1.1 Compression OCE
          9.13.1.2 Surface wave/shear wave OCE
     9.2.2 OCE probes
9.14 Acoustically Modulated Speckle Imaging
9.15 Conclusions
References

10 Optical Clearing of Tissues: Benefits for Biology, Medical Diagnostics, and Phototherapy
E. A. Genina, A. N. Bashkatov, Yuri P. Sinichkin, I. Yu. Yanina, and V. V. Tuchin
10.1 Fundamentals of Optical Clearing (OC) of Tissues and Cells
10.2 Immersion OC
10.3 Compression OC
10.4 Photochemical, Thermal, and Photothermal OC
10.5 Applications in Biology and Medicine
     10.5.1 Optical coherence tomography
     10.5.2 Optical projection tomography
     10.5.3 Fluorescence imaging
     10.5.4 Photoacoustic imaging
     10.5.5 Nonlinear and Raman microscopy
     10.5.6 Terahertz spectroscopy
10.6 Determination of OCA and Drug Diffusion Coefficients in Tissues
10.7 Conclusion
References


Preface

This Handbook is the second edition of the monograph initially published in 2002. The first edition described some aspects of laser/cell and laser/tissue interactions that are basic for biomedical diagnostics and presented many optical and laser diagnostic technologies prospective for clinical applications. The main reason for publishing such a book was the achievements of the last millennium in light scattering and coherent light effects in tissues, and in the design of novel laser and photonics techniques for the examination of the human body. Since 2002, biomedical optics and biophotonics have had rapid and extensive development, leading to technical advances that increase the utility and market growth of optical technologies. Recent developments in the field of biophotonics are wide-ranging and include novel light sources, delivery and detection techniques that can extend the imaging range and spectroscopic probe quality, and the combination of optical techniques with other imaging modalities.

The innovative character of photonics and biophotonics is underlined by two Nobel prizes in 2014 awarded to Eric Betzig, Stefan W. Hell, and William E. Moerner�"for the development of super-resolved fluorescence microscopy" and to Isamu Akasaki, Hiroshi Amano, and Shuji Nakamura�"for the invention of efficient blue light-emitting diodes which has enabled bright and energy-saving white light sources." The authors of this Handbook have a strong input in the development of new solutions in biomedical optics and biophotonics and have conducted cutting-edge research and developments over the last 10 - 15 years, the results of which were used to modify and update early written chapters. Many new, world-recognized experts in the field have joined the team of authors who introduce fresh blood in the book and provide a new perspective on many aspects of optical biomedical diagnostics.

The optical medical diagnostic field covers many spectroscopic and laser technologies based on near-infrared (NIR) spectrophotometry, fluorescence and Raman spectroscopy, optical coherence tomography (OCT), confocal microscopy, optoacoustic (photoacoustic) tomography, photon-correlation spectroscopy and imaging, and Doppler and speckle monitoring of biological flows. These topics - as well as the main trends of the modern laser diagnostic techniques, their fundamentals and corresponding basic research on laser�tissue interactions, and the most interesting clinical applications - are discussed in the framework of this Handbook. The main unique features of the book are as follows:

  1. Several chapters of basic research that discuss the updated results on light scattering, speckle formation, and other nondestructive interactions of laser light with tissue; they also provide a basis for the optical and laser medical diagnostic techniques presented in the other chapters.
  2. A detailed discussion of blood optics, blood and lymph flow, and blood-aggregation measurement techniques, such as the well-recognized laser Doppler method, speckle technique, and OCT method.
  3. A discussion of the most-recent prospective methods of laser (coherent) tomography and spectroscopy, including OCT, optoacoustic (photoacoustic) imaging, diffusive wave spectroscopy (DWS), and diffusion frequency-domain techniques.

The intended audience of this book consists of researchers, postgraduate and undergraduate students, biomedical engineers, and physicians who are interested in the design and applications of optical and laser methods and instruments for medical science and practice. Due to the large number of fundamental concepts and basic research on laser�tissue interactions presented here, it should prove useful for a much broader audience that includes students and physicians, as well. Investigators who are deeply involved in the field will find up-to-date results for the topics discussed. Each chapter is written by representatives of the leading research groups who have presented their classic and most recent results. Physicians and biomedical engineers may be interested in the clinical applications of designed techniques and instruments, which are described in a few chapters. Indeed, laser and photonics engineers may also be interested in the book because their acquaintance with a new field of laser and photonics applications can stimulate new ideas for lasers and photonic devices design. The two volumes of this Handbook contain 21 chapters, divided into four parts (two per volume):

  • Part I describes the fundamentals and basic research of the extinction of light in dispersive media; the structure and models of tissues, cells, and cell ensembles; blood optics; coherence phenomena and statistical properties of scattered light; and the propagation of optical pulses and photon-density waves in turbid media. Tissue phantoms as tools for tissue study and calibration of measurements are also discussed.
  • Part II presents time-resolved (pulse and frequency-domain) imaging and spectroscopy methods and techniques applied to tissues, including optoacoustic (photoacoustic) methods. The absolute quantification of the main absorbers in tissue by a NIR spectroscopy method is discussed. An example biomedical application - the possibility of monitoring brain activity with NIR spectroscopy - is analyzed.
  • Part III presents various spectroscopic techniques of tissues based on elastic and Raman light scattering, Fourier transform infrared (FTIR), and fluorescence spectroscopies. In particular, the principles and applications of backscattering diagnostics of red blood cell (RBC) aggregation in whole blood samples and epithelial tissues are discussed. Other topics include combined back reflectance and fluorescence, FTIR and Raman spectroscopies of the human skin in vivo, and fluorescence technologies for biomedical diagnostics.
  • The final section, Part IV, begins with a chapter on laser Doppler microscopy, one of the representative coherent-domain methods applied to monitoring blood in motion. Methods and techniques of real-time imaging of tissue ultrastructure and blood flows using OCT is also discussed. The section also describes various speckle techniques for monitoring and imaging tissue, in particular, for studying tissue mechanics and blood and lymph flow.

Financial support from a FiDiPro grant of TEKES, Finland (40111/11) and Academic D.I. Mendeleev Fund Program of Tomsk National Research State University have helped me complete this book project. I greatly appreciate the cooperation and contribution of all of the authors and co-editors, who have done a great work on preparation of this book. I would like to express my gratitude to Eric Pepper and Tim Lamkins for their suggestion to prepare the second edition of the Handbook and to Scott McNeill for assistance in editing the manuscript. I am very thankful to all of my colleagues from the Chair and Research Education Institute of Optics and Biophotonics at Saratov National Research State University and the Institute of Precision Mechanics and Control of RAS for their collaboration, fruitful discussions, and valuable comments. I am very grateful to my wife and entire family for their exceptional patience and understanding.

Valery V. Tuchin
May 2016


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