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Handbook of Optical Biomedical Diagnostics, Second Edition, Volume 1: Light-Tissue Interaction
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 1: Light - Tissue Interaction features eleven chapters, five of which focus on the fundamental physics of light propagation in turbid media such as biological tissues. The six following chapters introduce near-infrared techniques for the optical study of tissues and provide a snapshot of current applications and developments in this dynamic and exciting field. Topics include the scattering of light in disperse systems, the optics of blood, tissue phantoms, a comparison between time-resolved and continuous-wave methods, and optoacoustics.

Buy this volume and Volume 2: Methods as a set at a discount! PM264

Book Details

Date Published: 25 October 2016
Pages: 864
ISBN: 9781628419092
Volume: PM262

Table of Contents
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Table of Contents

List of Contributors

Part I: Light-Tissue Interaction: Diagnostic Aspects
Dmitry A. Zimnyakov and Lihong V. Wang

1 Introduction to Light Scattering by Biological Objects
Nikolai G. Khlebtsov, Irina L. Maksimova, Igor Meglinski, Lihong V. Wang, and Valery V. Tuchin
1.1 Introduction
1.2 Extinction and Scattering of Light in Disperse Systems: Basic Theoretical Approaches
1.3 Theoretical Methods for Single-Particle Light-Scattering Calculations
     1.3.1 Basic parameters for single-particle light scattering
     1.3.2 Exact analytical and numerical methods
 Separation of variables and T-matrix methods (SVM and TM)
 Integral equation method (IEM)
 Discrete dipole approximation (DDA)
     1.3.3 Approximate theories
 Rayleigh approximation
 Rayleigh-Debye-Gans (RDG) approximation
 Anomalous diffraction (AD) and related approximations
     1.3.4 Other methods and approximations
1.4 Extinction and Scattering by Aggregated and Compounded Structures
     1.4.1 Approximate and DDA methods
     1.4.2 Superposition method
     1.4.3 T-matrix formalism for cluster scattering
     1.4.4 Fractal aggregates
1.5 Extinction and Scattering by Plasmon-Resonant Particles
     1.5.1 Localized plasmon resonance of small metal spheres
     1.5.2 Metal nanorods
     1.5.3 Metal nanoshells
     1.5.4 Coupled plasmon resonances: bisphere and linear chain examples
1.6 Tissue Structure and Relevant Optical Models
     1.6.1 Continuous and discrete models of tissues
     1.6.2 Shape and sizes of particles in discrete tissue models
     1.6.3 Optical constants of tissues, heterogeneity, and optical softness
     1.6.4 Anisotropy of tissues
     1.6.5 Volume fraction of the particles
     1.6.6 Effects of spatial ordering
     1.6.7 Fractal properties of tissues
1.7 Light Scattering by Densely Packed Correlated Particles
     1.7.1 Pair distribution function g(r)
     1.7.2 Light scattering by a system of particles in the single scattering approximation
     1.7.3 Angular characteristics for polarized light scattering
     1.7.4 Spectral characteristics of scattering systems
     1.7.5 Consideration of multiple scattering effects in the system of densely packed particles
     1.7.6 Birefringence of a system of anisotropic particles
1.8 Application of Radiative Transfer Theory to Tissue Optics
     1.8.1 Approximation methods for solution of the radiation transfer equation
 The first-order approximation
 Diffusion approximation
 Small-angular approximation
 Flux theory
 Vector radiative transfer equation
     1.8.2 Monte Carlo simulation
 Simulation algorithm
 Calculation of LSM for multiple scattering system
 Degree of linear and circular polarization of light interacting with tissues
 Simulation of two-dimensional reflection and transmission LSM
 Simulation of the spectra of transmission, reflection, and scattering
1.9 Nephelometry and Polarization Methods for the Diagnostics of Bio-objects
     1.9.1 Relations between the LSM elements: depolarization criterion
     1.9.2 Angular dependence of the scattering intensity of nondepolarized light
     1.9.3 Measurements of the angular dependences of the scattering matrix elements
     1.9.4 The LSM for some biological objects
     1.9.5 Effects of circular light probing and optical activity
1.10 Controlling of Optical Properties of Tissues
1.11 Circularly Polarized Light
1.12 Summary

2 Optics of Blood
Anna N. Yaroslavsky and Ilya V. Yaroslavsky
2.1 Introduction
2.2 Physical Properties of Blood Cells
     2.2.1 Red blood cells
     2.2.2 Leukocytes
     2.2.3 Platelets
2.3 Optical Properties of Oxy-hemoglobin and Deoxy-hemoglobin
2.4 Absorption and Scattering of Light by a Single Erythrocyte
     2.4.1 Absorption and scattering cross-sections, scattering phase function
     2.4.2 Experimental determination of blood extinction coefficient and scattering phase function
     2.4.3 Analytical and numerical methods to approximate single light scattering in blood
 Mie theory
 WKB approximation
 RGD approximation
 Fraunhofer and anomalous diffraction approximations
 Semi-analytical and numerical methods
 Empirical phase functions
2.5 Optical Properties of Blood
     2.5.1 Integrating sphere technique
     2.5.2 Blood preparation and handling
     2.5.3 Algorithms used to determine optical properties of whole and diluted human blood from the integrating sphere measurements
 The Monte Carlo method
 The adding-doubling method
2.6 Summary of the Optical Properties of Diluted and Whole Human Blood
     2.6.1 Optical properties of blood determined using direct techniques
     2.6.2 Optical properties of blood determined using indirect techniques
2.7 Practical Relevance of Blood Optics

3 Propagation of Pulses and Photon Density Waves in Turbid Media
Ilya V. Yaroslavsky, Anna N. Yaroslavsky, and Juan Rodriguez
3.1 Introduction
3.2 Time-Dependent Transport Theory
3.3 Techniques for Solving the Time-Dependent Transport Equation
     3.3.1 Reduction to steady-state case
     3.3.2 Spherical harmonics method
     3.3.3 Discrete ordinate method
     3.3.4 Distributed-source approach
3.4 Monte Carlo Method
     3.4.1 Sampling of random variables
     3.4.2 Generic time-resolved Monte Carlo algorithm
     3.4.3 Photon weighting
     3.4.4 Shortcut technique in the frequency domain
     3.4.5 Local estimate technique
     3.4.6 Hybrid technique
3.5 Diffusion approximation
     3.5.1 Time-dependent diffusion equation
     3.5.2 Solutions for simple geometries
 Infinite medium
 Semi-infinite medium
     3.5.3 Numerical techniques
3.6 Beyond Diffusion Approximation
3.7 Role of the Single-Scattering Delay Time
3.8 Concluding Remarks

4 Coherence Phenomena and Statistical Properties of Multiply Scattered Light
Dmitry A. Zimnyakov
4.1 Introduction
4.2 Weak Localization of Light in Disordered and Weakly Ordered Media
4.3 Correlation Properties of Multiple-Scattered Coherent Light: Basic Principles and Methods
     4.3.1 Theoretical background for correlation analysis of multiple-scattered dynamic speckles
     4.3.2 Diffusing-wave spectroscopies and related techniques
4.4 Evaluation of the Pathlength Density: Basic Approaches
     4.4.1 The concept of the pathlength density for description of light propagation in disordered media
     4.4.2 Diffusion approximation
     4.4.3 Other approaches
4.5 Manifestations of Self-similarity in Multiple Scattering of Coherent Light by Disordered Media
4.6 Diagnostic Applications of Light Coherence Phenomena in Multiple Scattering: Recent Applications in Biomedicine and Material Science
4.7 Conclusion

5 Tissue Phantoms
Alexander B. Pravdin, George Filippidis, Giannis Zacharakis, Theodore G. Papazoglou, and Valery V. Tuchin
5.1 Introduction
5.2 General Approaches to Phantom Development
     5.2.1 Basic concept
     5.2.2 Mie theory predictions for scattering and absorption properties of particle suspensions
5.3 Scattering Media for Phantom Preparation
     5.3.1 Fat emulsions as scattering media in tissue phantoms
     5.3.2 Milk in phantoms
     5.3.3 Polymer latex spheres in construction of tissue-like phantoms
     5.3.4 Mineral particles as scatterers in solid phantoms
5.4 Light-Absorbing Media for Phantom Preparation
     5.4.1 Common microscopy stains in liquid and solid phantoms
     5.4.2 Dyes as light-absorbing components of tissue-simulating phantoms
     5.4.3 Inorganic ions as absorbers in solid and liquid tissue phantoms
     5.4.4 From the dyes to pigments and absorbing particles in phantoms
     5.4.5 Phantoms containing hemoglobin
5.5 Smart Phantoms
     5.5.1 Multifunctional phantoms
     5.5.2 Phantoms mimicking vascular systems
     5.5.3 Phantoms of organs
5.6 Phantoms with Optically Active Media
     5.6.1 Introduction
     5.6.2 Optically active tissue phantoms
     5.6.3 Conclusion
5.7 Summary

Part II: Tissue Near-Infrared Spectroscopy and Imaging
Sergio Fantini and Ilya V. Yaroslavsky

6 Time-Resolved Imaging in Diffusive Media
Heidrun Wabnitz, Juan Rodriguez, Ilya Yaroslavsky, Anna Yaroslavsky, Harold Battarbee, and Valery V. Tuchin
6.1 Introduction
     6.1.1 Looking through turbid tissues with conventional imaging techniques
     6.1.2 Sharpening images in diffusive media: the early history of the time-resolved method
6.2 General Concepts in Time-Resolved Imaging through Highly Diffusive Media
     6.2.1 Transmittance methods
 Time-gated shadowgraphs
 Diffuse transmittance imaging
     6.2.2 Time-resolved optical tomography
 The back-projection technique
 Diffuse tomography methods
     6.2.3 Depth-resolved imaging
 Coherent backscattering
 Diffuse reflectance imaging
6.3 Experimental Tools for Time-Resolved Imaging
     6.3.1 General considerations
     6.3.2 Pulsed light sources
 Mode-locked lasers
 Pulsed semiconductor lasers
 Other laser systems
     6.3.3 Detection systems based on time-correlated single-photon counting
 TCSPC principle
 Detectors for TCSPC
     6.3.4 Other high-speed detection systems
 Streak cameras
 Gated cameras
     6.3.5 Light guides
6.4 Technical Designs for Time-Resolved Imaging
     6.4.1 Transmittance imaging
 Time-gated 2D projections
 Diffuse transmittance imaging
     6.4.2 Time-resolved optical tomography
     6.4.3 Reflectance imaging
 Depth-resolved coherence imaging
 Diffuse reflectance imaging
6.5 Toward Clinical Applications
     6.5.1 Time-domain optical mammography
     6.5.2 Time-domain optical brain imaging
 Optical tomography of the infant brain
 Functional optical brain imaging and cerebral oximetry in adults
 Perfusion assessment by ICG bolus tracking
6.6 Conclusions

7 Frequency-Domain Techniques for Tissue Spectroscopy and Imaging
Sergio Fantini and Angelo Sassaroli
7.1 Introduction
7.2 Instrumentation, Modulation Methods, and Signal Detection
     7.2.1 Light sources and modulation techniques
     7.2.2 Pulsed sources
     7.2.3 Optical detectors
     7.2.4 Homodyne and heterodyne detection
     7.2.5 A frequency-domain tissue spectrometer
7.3 Frequency-Domain Diffusion Theory for Quantitative Tissue Spectroscopy
     7.3.1 The Boltzmann transport equation (BTE)
     7.3.2 Derivation of the diffusion equation (DE) from the BTE
     7.3.3 The diffusion equation in the frequency domain
     7.3.4 Solutions to the frequency-domain diffusion equation
 Infinite geometry
 Semi-infinite geometry
 Two-layered geometry
     7.3.5 Multi-distance tissue spectroscopy
     7.3.6 Multi-frequency tissue spectroscopy
7.4 Tissue Spectroscopy and Oximetry
     7.4.1 Optical properties of biological tissue
     7.4.2 Absorption spectroscopy of tissue
     7.4.3 Quantification of hemoglobin concentration and saturation in tissue
     7.4.4 Absolute brain measurements with semi-infinite and two-layer models
     7.4.5 Measurements of optical scattering in tissue
7.5 Optical Imaging of Tissues
     7.5.1 General concepts
     7.5.2 The phase information in frequency domain optical imaging
     7.5.3 Optical mammography and other applications
     7.5.4 Imaging of finger joints
7.6 Prospects for Frequency-Domain Spectroscopy and Imaging of Tissue

8 Monitoring of Brain Activity with Near-Infrared Spectroscopy
Hui Gong, Qingming Luo, Shaoqun Zeng, Shoko Nioka, Yasufumi Kuroda, and Britton Chance
8.1 Introduction
     8.1.1 Brain mapping by time-resolved and frequency-domain imaging systems
     8.1.2 The concepts of NIRS signal as a measure of neuronal activities
8.2 Continuous Wave Functional Near-Infrared Imager
     8.2.1 Photon migration
     8.2.2 Instrumentation and performance
8.3 Monitoring of Human Brain Activity with CW Functional Optical Imager
     8.3.1 Motor cortex in finger tapping
     8.3.2 n-back test
     8.3.3 The study of developmental dyslexia children
     8.3.4 Stem recognition performance measurement
     8.3.5 Pinpoint source location for ocular nonselective attention
     8.3.6 Cognitive conflict control
     8.3.7 Motor skill learning
     8.3.8 Thinking process and learning: "insight signal" through verbal stimuli
     8.3.9 PFC responses to emotional stresses
     8.3.10 Optical neuronal signals in the visual cortex
8.4 Future Prospects

9 Signal Quantification and Localization in Tissue Near-Infrared Spectroscopy
Stephen J. Matcher
9.1 Introduction
9.2 Oximetry
     9.2.1 Optical spectroscopy
     9.2.2 Noninvasive hemoglobin spectroscopy
     9.2.3 Near-infrared spectroscopy (NIRS)
9.3 Tissue Near-Infrared Spectroscopy
     9.3.1 Oxygen-dependent chromophores
 Cytochrome-aa3 (cytochrome-oxidaze)
     9.3.2 Oxygen-independent chromophores
 Other cytochromes
9.4 Spectroscopy in a Highly Scattering Medium
9.5 Absolute Measurements
     9.5.1 Use of a "forward model" of light transport
 Spatially resolved spectroscopy (SRS)
 Time-resolved spectroscopy (TRS)
 The microscopic Beer-Lambert law
 Practical TRS systems and their applications
 Frequency-domain spectroscopy
     9.5.2 Chemometric methods
9.6 Quantified Trend Measurements
     9.6.1 Determination of the DPF at a given wavelength
 Time-resolved methods
 Time-domain measurements
 Frequency-domain measurements
 "Tracer" methods
     9.6.2 Determination of the wavelength dependence of pathlength
     9.6.3 Instrumentation
     9.6.4 Algorithms
 The "UCL" algorithm
 The "SAPPORO" algorithm
 The "DUKE-P" algorithm
 The "KEELE" algorithm
 Algorithm comparison
9.7 Use of Quantified Trend Measurements to Infer Absolute Blood Flow, Blood Volume, Hemoglobin Saturation, and Tissue Oxygen Consumption
     9.7.1 Venous saturation via venous occlusion plethysmography
     9.7.2 Skeletal muscle blood flow
     9.7.3 Absolute muscle oxygen consumption
     9.7.4 Cerebral blood flow (CBF)
     9.7.5 Cerebral blood volume (CBV)
9.8 Effects of Tissue Geometry and Heterogeneity
     9.8.1 Light transport models
 Two-layer diffusion models
 The Monte Carlo model
 The finite-element method
 Hybrid diffusion-radiosity models
 Discrete absorber models
     9.8.2 Effects of tissue heterogeneity
 Quantified trend
 Absolute measurements
     9.8.3 Summary
9.9 Chapter Summary
9.10 Recent Developments

10 Near-Infrared Spectroscopy in Multimodal Brain Research
Teemu Myllyla, Vladislav Toronov, Jurgen Claassen, Vesa Kiviniemi, and Valery V. Tuchin
10.1 Introduction
     10.1.1 Functional imaging of the brain
     10.1.2 Towards multimodality
10.2 Realization of NIRS in Multimodal Setups
     10.2.1 NIRS head caps
10.3 fNIRS Combined with Different Techniques: Possibilities and Challenges
     10.3.1 fNIRS and neuroimaging
     10.3.2 Blood pressure and cerebral blood flow
10.4 Novel Approaches and Examples of Current Multimodal studies
     10.4.1 Combining TCD with fNIRS
     10.4.2 Development of hyperspectral fNIRS
     10.4.3 Brain imaging utilizing fNIRS combined with seven modalities
10.5 Enhancement of In-Depth NIRS Imaging
     10.5.1 Transmittance of cranium tissues in the NIR
     10.5.2 Optical clearing of tissues
     10.5.3 OCA diffusion
     10.5.4 In vivo optical clearing of skull
10.6 Chapter Summary

11 Measurement of Optical Fluence Distribution and Optical Properties of Tissues Using Time-Resolved Profiles of Optoacoustic Pressure
Ivan M. Pelivanov, Alexander A. Karabutov, Tatiana D. Khokhlova, and Alexander A. Oraevsky
11.1 Methods to Study Light Distribution in Tissue
11.2 Two Modes of Optoacoustic Detection
11.3 Stages of the Optoacoustic Phenomena
11.4 Specific Features of Depth Distribution of the Absorbed Optical Energy in Optically Scattering Media
     11.4.1 Monte Carlo method
     11.4.2 Analytical approach: solution of light transfer equation in the 3P and 5P approximations
11.5 Time-Resolved Optoacoustic Measurement of Depth Distribution of the Absorbed Optical Energy and Optical Properties in Scattering Media
     11.5.1 Temporal profile of the LIP
     11.5.2 Diffraction transformation of the LIP
     11.5.3 Absorbed optical energy profiles measured in forward mode
     11.5.4 Determination of the effective optical attenuation, absorption, and reduced scattering coefficients
     11.5.5 Possibility of in vivo measurements of tissue's optical properties in backward mode
11.6 Technical Requirements for Time-Resolved Optoacoustic Detection
11.7 Summary and Biomedical Applications


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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