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Deep Imaging in Tissue
and Biomedical Materials
Deep Imaging in Tissue
and Biomedical Materials
Using Linear and Nonlinear Optical Methods

editors
edited by
Preben Maegaard Lingyan Shi
Anna Krenz
Wolfgang Palz Robert
RobertR.Alfano
Alfano

The Rise of Modern Wind Energy

Wind Power
for the World
Published by
Pan Stanford Publishing Pte. Ltd.
Penthouse Level, Suntec Tower 3
8 Temasek Boulevard
Singapore 038988

Email: editorial@panstanford.com
Web: www.panstanford.com

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Deep Imaging in Tissue and Biomedical Materials: Using Linear

and Nonlinear Optical Methods
Copyright © 2017 Pan Stanford Publishing Pte. Ltd.

All rights reserved. This book, or parts thereof, may not be reproduced in any
form or by any means, electronic or mechanical, including photocopying,
recording or any information storage and retrieval system now known or
to be invented, without written permission from the publisher.

For photocopying of material in this volume, please pay a copying fee

through the Copyright Clearance Center, Inc., 222 Rosewood Drive,
Danvers, MA 01923, USA. In this case permission to photocopy is not
required from the publisher.

Cover image, taken by Lingyan Shi from Adrian Rodriguez-Contreras’

Lab, shows a trans-cranial image of brain microvessels filled up with
Texas red dextran 70 kDa and wrapped with Gcamp-6 GFAP astrocytes,
using multiphoton fluorescence microscope.

ISBN 978-981-4745-88-8 (Hardcover)

ISBN 978-1-315-20655-4 (eBook)

Printed in the USA

 Contents

Preface xvii

1. Overview of Second- and Third-Order Nonlinear

Optical Processes for Deep Imaging 1
Sangeeta Murugkar and Robert W. Boyd

1.1 Introduction: Nonlinear Optical Contrast in

Biological Imaging 1
1.2 Classical Description of Nonlinear Light–Matter
Interaction 4
1.3 Second Harmonic Generation 5
1.3.1 Quantum Mechanical Treatment of the
Nonlinear Susceptibility 7
1.3.2 Wave Equation Description of SHG 8
1.3.3 Symmetry Breaking and SHG Signal in
Biological Imaging 9
1.4 Coherent Raman Scattering 9
1.4.1 Classical Model of Spontaneous Raman
Scattering 10
1.4.2 Classical Model of Coherent Raman
Scattering 11
1.4.3 CARS Signal Generation in the Plane Wave
Approximation 14
1.4.4 SRS Microscopy 16
1.5 Two-Photon Absorption 19
1.6 Supercontinuum Generation 21
1.6.1 Supercontinuum Generation in Bulk Media 21
1.6.2 Supercontinuum Generation in Optical Fibers 24
1.7 Conclusion 25
vi Contents

2. Complex Light Beams 31

Enrique J. Galvez

2.1 Introduction 31
2.2 Gaussian Beams 32
2.2.1 Fundamental Gaussian Beams 32
2.2.1.1 The beam spot w 35
2.2.1.2 Beam intensity 37
2.1.1.3 Wavefront 39
2.1.1.4 Gouy phase 39
2.1.1.5 Momentum 40
2.1.1.6 Gaussian-beam optics 42
2.2.2 Hermite–Gaussian Beams 44
2.2.3 Laguerre–Gaussian Beams 47
2.2.3.1 Fundamentals 47
2.2.3.2 Interference 50
2.2.3.3 Angular momentum 52
2.2.4 Relations between Mode Families 54
2.2.5 Laboratory Methods of Production 57
2.2.5.1 Spiral phase plate 58
2.2.5.2 Holographic diffraction 59
2.3 Non-Diffracting Optical Beams 61
2.3.1 Bessel Beams 62
2.3.2 Airy Beams 66
2.4 Beams with Space-Variant Polarization 68
2.4.1 Polarization 68
2.4.2 Vector Beams 71
2.4.3 Poincaré Beams 73
2.5 Discussion and Conclusions 75

3. Gaussian Beam Optical Parameters in Multi-Photon

Excitation Fluorescence Imaging 81
Lingyan Shi, Adrián Rodríguez-Contreras, and Robert R. Alfano

3.1 Introduction 82
3.2 Gaussian Beam Model 82
3.3 Parameters in Multiphoton Imaging 84
 Contents vii

4. The Optics of Deep Optical Imaging in Tissues Using

Long Wavelengths 91
Steven L. Jacques

4.1 Introduction 92
4.2 Monte Carlo Simulations 95
4.2.1 Modeling Light Penetration into a
Thick Tissue 95
4.2.2 Modeling the Shi Experiment of Narrow
Transmission Using Thin Tissues 97
4.2.3 Summary of Results 98
4.3 Discussion 99

5. Light Propagation and Interaction in Highly Scattering

Media for Deep Tissue Imaging 107
W. B. Wang, Lingyan Shi, Luyao Lu, Laura A. Sordillo, L. Wang,
S. K. Gayen, and R. R. Alfano

5.1 Introduction 108

5.2 Physics of Light Propagation for Imaging through
a Highly Scattering Medium 110
5.2.1 Components of Transmitted Light from
Scattering Media 111
5.2.2 Key Optical Parameters for Describing Light
Propagation in Highly Scattering Media 114
5.2.3 Values of Key Optical Parameters for
Human Tissues and Some Model Media 117
5.2.4 Optical Absorption Spectra of Key
Chromophores in Tissues 121
5.3 Study of Ballistic and Diffuse Light Components 123
5.4 NIR Absorption 130
5.5 Transition from Ballistic to Diffuse in Model
Scattering Media and Brain 135
5.6 Propagation and Scattering of Vortex Light
Beam with Optical Angular Momentum in
Turbid Media 138
5.7 Nonlinear Optical Subsurface Imaging of Tissues 143
5.8 Summary 147
viii Contents

6. Application of Nonlinear Microscopy in Life Sciences 157

Zdenek Svindrych and Ammasi Periasamy

6.1 Introduction 158

6.2 Basic Principles of Multiphoton Microscopy 159
6.2.1 The Missing Cone Problem 159
6.2.2 Confocal Detection 160
6.2.3 Multiphoton Microscopy 161
6.2.4 Second Harmonic Generation 164
6.2.5 Absorption, Scattering and Wavefront
Distortion in Tissues 165
6.3 Instrumentation for Nonlinear Microscopy 167
6.3.1 Light Sources in Nonlinear Microscopy 167
6.3.2 Point Scanning Nonlinear Microscopy 168
6.3.3 Multipoint Scanning Two-Photon
Microscopy 170
6.3.4 Line Scanning Nonlinear Microscopy 170
6.3.5 Temporal Focusing 171
6.3.6 Two-Photon Selective Plane Illumination
Microscopy 172
6.3.7 Superresolution Nonlinear Microscopy 172
6.3.8 Opto-Acoustic Intravital Imaging with
Multiphoton Excitation 173
6.3.9 Multiphoton Endoscopy with GRIN
Needle Lenses 173
6.3.10 Intravital 2P Microscopy with Optical Fibers 174
6.3.11 Fluorescence Lifetime Imaging
Microscopy 176
6.4 Biological Applications of Nonlinear Microscopy 178
6.4.1 Application of Nonlinear Microscopy in
Neuroscience 178
6.4.2 Nonlinear Microscopy in Cancer Research 180
6.4.3 Multiphoton Microscopy in Developmental
Biology 181
6.4.4 Nonlinear Microscopy in Tissue Engineering 182
 Contents ix

6.4.5
Deep Tissue FRET Imaging 184
6.4.6
Multiphoton Imaging of Endogenous
Molecules 185
6.5 Conclusion 188

7. Smart Biomarker-Coated PbS Quantum Dots for

Deeper Near-Infrared Fluorescence Imaging in the
Second Optical Window 203
Takashi Jin, Akira Sasaki, and Yukio Imamura

7.1 Introduction 203

7.2 Optical Properties of Tissues 206
7.3 NIR Probes in First and Second Optical Window 208
7.4 Synthesis of Quantum Dots 210
7.4.1 Highly Fluorescent PbS/CdS QDs 210
7.4.2 Water-Soluble PbS QDs 212
7.4.3 Dual Emitting PbS QDs 213
7.5 Non-Invasive Fluorescence Imaging 215
7.5.1 Lymph System 215
7.5.2 Cerebral Blood Vessels 217
7.5.3 Breast Tumor 218
7.5.4 Phagocytic Cell Migration 219
7.6 Future Prospects 220

8. Biomedical Applications in Probing Deep Tissue

Using Mid-Infrared Supercontinuum Optical Biopsy 231
Angela B. Seddon

8.1 Mid-Infrared Electromagnetic Spectral Region 232

8.2 MIR Spectroscopy 233
8.3 Motivation and Aspiration 240
8.4 Raman Spectroscopy vis-à-vis MIR Spectroscopy
for Medical Spectral Imaging 247
8.4.1 Active and Passive MIR Chalcogenide
Glass Fibers 252
8.5 MIR Light Molecular Spectral Imaging on
Excised Tissue 253
 Contents

8.5.1
MIR Light Spectral Imaging of Excised
External Tissue 254
8.5.2 MIR Light Spectral Imaging of Excised
Internal Tissue 258
8.5.3 MIR Light Coherent Imaging 264
8.6 How to Achieve the in vivo MIR Optical Biopsy 264
8.6.1 MIR Optical Components, Circuits
and Detectors 265
8.6.1.1 MIR optical components and
circuits 265
8.6.1.2 MIR detectors 265
8.6.2 MIR Light Sources: Traditional, Emerging
and New 266
8.6.3 Progress on MIR Fiber Lasers: MIR
Supercontinuum Generation 272
8.6.3.1 MIR supercontinuum generation
wideband fiber lasers 272
8.6.3.2 MIR Narrowline Direct-Emission
Fiber Lasers 279
8.7 Summary and Future Prospects 280

9. Light Propagation in Turbid Tissue-Like Scattering Media 295

Alexander Bykov, Alexander Doronin, and Igor Meglinski

9.1 Introduction 296

9.2 Light Scattering Characteristics of Biotissues 296
9.3 Radiative Transfer Equation 299
9.4 Approximations of the Radiative Transfer 300
9.4.1 Small-Angular Approximation 301
9.4.2 Diffuse Approximation 301
9.4.3 Other Methods and Approximations 303
9.5 Monte Carlo Simulations 303
9.5.1 Theoretical Basis for Modeling of Coherent
Polarized Light Propagation in Scattering
Media 305
9.5.1.1 Linearly polarized light 306
9.5.1.2 Circularly polarized light 309
 Contents xi

9.5.2
Results of Modeling of Polarized Light
Propagation 311
9.6 Summary 316

10. Overview of the Cumulant Solution to Light Propagation

Inside a Turbid Medium and Its Applications in
Deep Imaging Beyond the Diffusion Approximation 323
Min Xu, Cai Wei, and Robert R. Alfano

10.1 Introduction 324

10.2 Derivation of Cumulants to an Arbitrary Order 326
10.3 Gaussian Approximation of the Distribution
Function 331
10.4 Applications of the Cumulant Solution of
Radiative Transfer 336
10.4.1 Transport Forward Model for Optical
Imaging 336
10.4.2 Early Photon Tomography 343
10.4.3 Non Medical Use of Retrieving Parameters
of Water Cloud from CALIPSO Data 344
10.2 Summary 349

11. Deep Imaging of Prostate Cancer Using Diffusion

Reconstruction of Banana Paths with Near Infrared
Prostatoscope Analyzer 353
Yang Pu, Wubao Wang, Min Xu, James A. Eastham,
and Robert R. Alfano

11.1 Introduction: Screening Cancer Using Light 353

11.2 Theoretical Formalism 356
11.2.1 Clean Image Synthesis 356
11.2.2 Numerical Target Marching 358
11.3 Experimental Setup and Methods 362
11.3.1 Design and Construction of Prostatoscope
Analyzer 362
11.3.2 Test Model and Prostate Samples 365
11.4 Experimental Results 368
11.5 Discussion and Conclusion 372
xii Contents

12. Terahertz Propagation in Tissues and Its Thickness

Limitation 377
Burcu Karagoz and Hakan Altan

12.1 Introduction 378

12.2 THz Generation and Detection 379
12.2.1 THz-TDS Method 380
12.2.2 Principles of THz-TDS 383
12.2.2.1 Measurements in
transmission geometry 387
12.2.2.2 Measurements in
reflection geometry 389
12.3 Soft Tissues 392
12.3.1 Brain Tissue 393
12.3.2 Skin, Muscle, and Adipose Tissue 393
12.3.3 Other Cancerous Tissue and Tumors 394
12.4 Hard Tissues 395
12.4.1 Bone 395
12.4.2 Cartilage 396
12.4.3 Teeth 397
12.5 Discussion and Conclusion 403

13. Detection of Brain Tumors Using Stimulated Raman

Scattering Microscopy 413
Spencer Lewis and Daniel Orringer

13.1 Introduction 413

13.2 Background 414
13.3 Preliminary Validation of SRS Microscopy in
Mouse Models 418
13.4 Preliminary Validation of SRS Microscopy in
Human Tissue 420
13.4.1 Qualitative Histology 420
13.4.2 Quantitative Analysis of Tumor Infiltration
with SRS 423
 Contents xiii

13.5 Other Intraoperative Microscopy Techniques

in Neurosurgery 426
13.6 Clinical Implementation of SRS Microscopy
and Future Work 427

14. Chemical and Molecular Imaging of Deep Tissue

through Photoacoustic Detection of Chemical
Bond Vibrations 431
Yingchun Cao and Ji-Xin Cheng

14.1 Introduction 431

14.2 Fundaments of Vibrational Photoacoustic
Imaging 433
14.2.1 Principle of Vibrational Photoacoustic
Imaging 433
14.2.2 Overtone Absorption Spectra of
Molecular Vibration 435
14.2.3 Multispectral Photoacoustic Imaging 437
14.3 Modalities of Vibrational Photoacoustic Imaging 440
14.4 Applications of Vibrational Photoacoustic Imaging 442
14.4.1 Breast Tumor Margin Assessment 443
14.4.2 Intravascular Imaging of Atherosclerotic
Plaque 445
14.5 Conclusions and Perspective 447

15. Deep Tissue Imaging: Acoustic and Thermal Wave

Propagation and Light Interactions in Tissue 457
Idan Steinberg, Asaf Shoval, Michal Balberg, Adi Sheinfeld,
Michal Tepper, and Israel Gannot

15.1 Introduction 458

15.2 Photoacoustics Quantitative Assessment of Deep
Tissue Functionality 458
15.2.1 Introduction 458
15.2.2 Deep Tissue Photoacoustic Flow
Measurements 460
xiv Contents

15.2.3 Photoacoustic Characterization of Bone

Pathologies for Early Detection of
Osteoporosis 464
15.3 Acousto-Optic Imaging in Deep Tissue 469
15.3.1 Introduction 469
15.3.2 Acousto-Optics in Turbid Media 469
15.3.3 Acousto-Optic Measurement of
Blood Flow 470
15.3.4 Acousto-Optic Measurements of Cerebral
Oxygen Saturation and Blood Flow in
Patients 472
15.4 Thermography for Assessment of Deep Tissue
Tumor Volumes and Monitoring of Diffused
Alpha Radiation Therapy 473
15.4.1 Introduction 473
15.4.2 Estimating Tumor Sizes from
Thermographic Imaging 474
15.4.3 Comparison of DART vs. Inert via
Thermography 475
15.5 Photothermal Techniques for Estimation of
Superficial and Deep Tissue Functionality 477
15.5.1 Introduction 477
15.5.2 Photothermal Monitoring of
Port-Wine-Stain Lesions 478
15.5.3 Photothermal Estimation of the
Oxygenation Level of Deep-Tissue 479

16. Using the Transmission Matrix to Image Disordered

Media 489
Matthieu Davy, Sylvain Gigan, and Azriel Z. Genack

16.1 Introduction 490

16.2 Distribution of Transmission Eigenvalues 491
16.2.1 Predictions 491
16.2.2 Measurements 494
 Contents xv

16.3 Eigenchannel Intensity Profiles 498

16.4 Wavefront Shaping for Imaging through
Turbid Media 502
16.5 Applications to Biomedical Imaging 507
16.5.1 Photoacoustic Transmission Matrix 507
16.5.2 Endoscopic Imaging in Multimode
Optical Fiber 508
16.6 Conclusion 509

Index 517
 Preface

The use of light for probing and imaging biomedical media is

promising for developing safe, noninvasive, and inexpensive clinical
imaging modalities with diagnostic ability. The advent of ultrafast
lasers enables the applications of nonlinear optical processes
for deeper imaging into biological tissues with higher spatial
resolution. The primary goals of this book are to review the
fundamentals in biophotonics and to introduce emerging novel
optical imaging techniques for deep tissue imaging. This book
is intended to serve as an introductory guide of optical imaging
for students and a reference for engineers and researchers who
seek a better understanding of deep imaging in tissues.
The book consists of 16 chapters and is divided into three
parts. Part I consists of eight chapters. The first chapter, by
Murugkar and Boyd, reviews the basic concepts of nonlinear
optical imaging, including second harmonic generation, coherent
Raman scattering, and self-phase modulation. The next chapter,
by Galvez, reviews the fundamentals and physical phenomena of
complex light beams, including Gaussian beam, Bessel beam, Airy
beam, and Poincare beam. The third chapter, by Shi and coworkers,
inspects the properties of Gaussian beam optics in multiphoton
fluorescence imaging. The deep imaging in the optical windows in
near-infrared (NIR) and short-wave infrared (SWIR) from 700 nm
to 2500 nm is reviewed by Jacques. Next, Alfano and coworkers
review the salient properties of light propagation in highly
scattering media and tissue. The application of non-linear
microscopy to life science is reviewed by Svindrych and Periasamy,
which is followed by the chapter on smart biomarker of quantum
dots for NIR fluorescence imaging by Jin, Sasaki, and Imamura.
The last chapter of Part I, by Seddon, describes biomedical
applications for deep probing in materials by using mid-infrared
supercontinuum laser and new optical fibers.
Part II reviews the theories and properties of light propagating
in tissue. The first chapter, by Bykov, Doronin, and Meglinski,
xviii Preface

overviews the theories and derived model for understanding

light propagation in tissue-like media using Monte Carlo. The
cumulant solution for light propagation in a turbid medium and
its applications in deep imaging are reviewed in the following
chapter by Xu, Cai, and Alfano. The final chapter of Part II, by Pu
and coworkers, reviews the latest advancement of NIR scanning
polarization imaging unit for prostate and presents an algorithm
for diffusive image reconstruction using NIR banana pathways.
Part III presents recent technology developments in optical
imaging and introduces the applications of different techniques
for detecting disordered media and tissue. Karagoz and Altan
introduce terahertz propagation in tissues and its limitation for
thick tissue and present ways for use in smears and thin tissues for
histology applications. The use of stimulated Raman scattering gain
and loss microscopy in detecting brain tumor is then reviewed by
Lewis and Orringer. The next chapter, by Cao and Cheng, introduces
the technology of using new photoacoustics approach for deep
imaging by detecting molecules’ vibrational overtone of chemical
bonds. Gannot and coworkers presents multiple acoustic and
thermal methods for light–tissue interaction for detecting deeper
structures. The final chapter, by Davy, Gigan, and Genack, describes
the properties of transmission matrix that determine the net
transmission pathways in biomedical and condensed media, and
its use for deep imaging.
As will be seen, much has been accomplished and reviewed in
the book, but much remains for the future. Therefore, not only is
this book an introduction to students in the field, but it proposes
directions for researchers to adapt their own or to explore new
optical technologies for deeper and better imaging in life science.
We wish to thank all the invited authors, who presented very
interesting and knowledgeable chapters.

Lingyan Shi
Robert R. Alfano
New York
January 2017
Chapter 1

Overview of Second- and Third-Order

Nonlinear Optical Processes for Deep
Imaging

Sangeeta Murugkara and Robert W. Boydb

aDepartment of Physics, Carleton University,
Ottawa, Ontario K1S 5B6, Canada
bDepartment of Physics, University of Ottawa,

Ottawa, Ontario K1N 6N5, Canada

smurugkar@physics.carleton.ca, rboyd@uottawa.ca

1.1 Introduction: Nonlinear Optical Contrast

in Biological Imaging
The field of optical microscopic imaging has rapidly evolved
because of tremendous advances made in laser and detection
technology. Various types of linear and nonlinear light–matter
interactions have been harnessed for providing contrast in the
microscopic images. Simple microscopy techniques such as
bright-field and differential-interference-contrast reveal structural
information at the cellular level owing to the refractive index
contrast of the sample medium. Fluorescence microscopy offers
higher chemical specificity and is the most popular contrast

Deep Imaging in Tissue and Biomedical Materials: Using Linear and Nonlinear Optical Methods
Edited by Lingyan Shi and Robert R. Alfano
Copyright © 2017 Pan Stanford Publishing Pte. Ltd.
ISBN 978-981-4745-88-8 (Hardcover), 978-1-315-20655-4 (eBook)
www.panstanford.com
 Second- and Third-Order Nonlinear Optical Processes

mechanism used in biological studies. The contrast is achieved

by means of targeted labeling of molecules using exogenous or
endogenous fluorophores. However, external fluorophores are
often perturbative since they may disrupt the native state of the
sample, especially for small molecules whose size may be smaller
than the fluorescent label itself. Besides, many molecular species
are intrinsically nonfluorescent or only weakly fluorescent.
It is also better to avoid external contrast agents for in vivo
imaging applications since such contrast agents need concurrent
development of appropriate delivery strategies and are often
limited by problems of label specificity and induced toxicity.
Vibrational microscopy techniques, on the other hand, are
inherently label-free. They involve the excitation of molecular
vibrations and offer intrinsic chemical specificity. Two such
techniques include infrared absorption and Raman microscopy.
Out of these, infrared microscopy has low spatial resolution
owing to the long infrared wavelengths employed. In addition,
water absorption of the infrared light is a major limitation for
investigating live biological samples. Raman scattering, on the
other hand, is based on the inelastic scattering of light by vibrating
molecules and provides a molecular fingerprint of the chemical
composition of a living cell or tissue. It offers a powerful label-free
contrast mechanism and has been applied in various biological
investigations. Linear contrast mechanisms based on fluorescence
and Raman scattering typically employ continuous-wave visible
light for excitation and sample scanning or laser scanning to
generate an image. A confocal pinhole inserted at the detector
facilitates a three-dimensionally sectioned image but unfortunately
limits the sensitivity of detection.
In comparison, nonlinear optical microscopy or multiphoton
microscopy employs near-infrared (near-IR) femtosecond or
picosecond pulsed light to excite nonlinear optical processes
that can only be accessed by application of two or more (multi)
photons [1]. The nonlinear optical signal is generated only in
the focal plane of the objective where the beam intensity is
maximized. This results in the inherent three-dimensional
sectioning capability without the need for a confocal pinhole.
This also means that significantly greater sensitivity in signal
detection is achieved since the confocal collection geometry is
not necessary. The near-IR light used for excitation of the
 Introduction 

nonlinear optical signal enables deeper penetration in thick

scattering samples and in addition is less biologically harmful.
In addition, multiphoton microscopic imaging can take advantage
of nonlinear optical processes involving endogenous contrast.
This ability permits dynamic studies of live cells and tissue
specimens in a label-free manner.
Two-photon-excited fluorescence (TPEF) or two-photon
microscopy has been extensively applied for biological imaging
over the past couple of decades [2, 3]. In TPEF, a single
femtosecond pulsed laser beam is tightly focused in the specimen
such that two low energy, near-IR photons are simultaneously
absorbed by a fluorophore and then emitted as one photon at
a higher frequency than the incident light. Along with TPEF,
nonlinear optical imaging techniques such as second harmonic
generation (SHG) and coherent Raman scattering (CRS) have
experienced continued growth in the technology and applications
over the past decade. In SHG, two photons with the same
frequency interacting with a nonlinear optical material are
effectively “combined” to generate new photons at twice the
frequency of the incident light [4]. CRS, which refers to both
stimulated Raman scattering (SRS) and coherent anti-Stokes
Raman scattering (CARS), is a technique to enhance spontaneous
Raman scattering. The spontaneous Raman effect involves
incoherent excitation of molecular vibrations. It is inherently
weak in nature with the typical photon conversion efficiencies for
Raman being lower than 1 in 1018. This results in long data
acquisition times of 100 ms to 1 s per pixel and does not permit fast
chemical imaging of a living system [5]. In contrast, CRS involves
nonlinear Raman scattering such that molecular vibrations are
driven coherently, in phase through stimulated excitation by
two synchronized femtosecond (or picosecond) pulsed lasers.
This translates to a reduction of the image acquisition time from
many minutes or hours required in confocal Raman microscopy
to only a couple of seconds using coherent Raman scattering
microscopy [6, 7]. CARS and SRS have been shown to be promising
techniques for the chemically selective imaging of lipids, proteins,
and DNA in skin, brain, and lung tissue. TPEF and SHG enable
selective imaging of auto-fluorescent proteins in tissue and
of noncentrosymmetric structures such as fibrillar collagen,
respectively [8]. We note that in many of these studies the
 Second- and Third-Order Nonlinear Optical Processes

illumination method of choice is one based on the nonlinear

optical process of supercontinuum generation (SCG).
In this chapter we examine the basics of second-order and
third-order nonlinear optical processes that are involved in
biological imaging, with the emphasis on second harmonic
generation, coherent Raman scattering and self-phase modulation
(SPM). We begin with a classical description of nonlinear light–
matter interaction in Section 1.2. This is followed by a summary
of the classical and quantum mechanical approach to explain SHG
signal generation in Section 1.3. The CRS process is described
for CARS and SRS signal generation in Section 1.4 while the two-
photon absorption process is described in Section 1.5. The process
of SCG and the related process of self phase modulation (SPM)
are described in Section 1.6.

1.2  Classical Description of Nonlinear

Light–Matter Interaction
Linear and nonlinear optical effects arise from the interaction of
the electric field associated with the incident light wave with
the charged particles of the material. The rapidly oscillating
applied electric field drives the motion of the bound electrons
in the molecules of the material. The displacement of the
electrons from their equilibrium positions induces an electric
P(t ) = N 
dipole moment m(t ).. The strength of this dipole moment is
higher for weakly bound electrons as compared to electrons that
are tightly bound to the nuclei of the molecules of the material.
The macroscopic polarization is then obtained by adding the
contributions of all N electric dipole moments induced in
the material and is given by

P(t ) = N 
m(t ). (1.1)
When the strength of the applied electric field is small compared
to that of the electric field binding the electrons to the nuclei,
i.e., in the weak field limit, the induced polarization can be
written assuming the case of rapid response as

P(t ) = e0 cE(t ), (1.2)

The tilde is used to denote a quantity that varies rapidly in time.
 Second Harmonic Generation 

where e0 is the electric permittivity in vacuum, c is the

susceptibility of the material P(t )and
= e0 cE(t ), is the electric field
associated with the incident light.
This type of linear dependence of the induced polarization
in the material on the magnitude of the applied electric field is
the source of all linear optical effects such as scattering,
reflectance, absorption, and fluorescence. The linearity of the
signal is defined through its linear dependence on the intensity
of the incident light. It is important to note that although
spontaneous Raman scattering is a linear effect, it can be
described as a nonlinear interaction between the photon fields
and the material as discussed later.
In the case of strong applied electric fields such as those
associated with femtosecond or picosecond pulsed lasers, the
induced polarization is not strictly linear and has higher orders
terms as follows:

P(t ) = e0[c(1) E(t ) + c(2) E (t ) + c(3) E (t ) + ... ]

2 3
(1.3)

Here c(1) is the linear susceptibility, c(2) is the second-order

susceptibility, c(3) is the third-order susceptibility, etc. Second-
harmonic generation occurs as a result of the second-order
response described by c(2), whereas the third-order response
described by c(3), is responsible for coherent Raman scattering
and two-photon excitation fluorescence.

1.3  Second Harmonic Generation

Second-harmonic generation is the prototypical nonlinear optical
process [1]. Its discovery by Franken and coworkers in 1961
[9] is often taken as the birth of the field of nonlinear optics. The
process of second-harmonic generation is illustrated in Fig. 1.1.
A laser beam at frequency w illuminates a nonlinear optical
material with a nonzero second-order susceptibility c(2), and a
beam of light at frequency 2w is created. The transfer of energy
from the input field to the output field can be depicted in terms
of the energy-level diagram shown on the right-hand side of
the figure. The solid line in this figure represents the atomic
ground state while the dashed lines represent virtual levels. In
this process, two photons from the input near-IR beam are
 Second- and Third-Order Nonlinear Optical Processes

lost and one photon in the output visible light beam is created.
Second harmonic generation is an example of a parametric
generation process since it involves the exchange of energy
between incident and outgoing laser fields while molecules
remain in the ground state after interaction. Other examples
of parametric processes that involve nonlinear electronic
polarization of the molecules under intense pulsed laser light
excitation are third-harmonic generation and four-wave mixing.
Coherent anti-Stokes Raman scattering (CARS) discussed in
Section 1.4 is an example of a nonlinear four-wave mixing
parametric process that involves the vibrational states of the
molecules.

(a) (b)

ω ω
ω (2)
χ 2ω 2ω

Figure 1.1 (a) Schematic representation of a second harmonic

generation process (b) Energy level diagram for SHG.
The bold line represents the ground electronic state of
the molecule while the dashed lines are virtual excited
states of the molecule.

The vector nature of the electric field and polarization needs

to be taken into account in order to get a more complete
description of the second-order nonlinear response. Besides, if
the various orders of the nonlinear susceptibility are frequency
dependent, the relationship between the electric field and
polarization is best expressed in the frequency domain. For
example, the second-order polarization can be expressed more
generally as

Pi (wn + wm ) = e0  c(2)
ijk (wn + wm , wn , wm ) E j (wn ) E k (wm ) (1.4)
jk (nm )

Here i, j, and k represent various Cartesian components of the

field vectors and the notation (n, m) implies that the expression
is to be summed over wn and wm but only those contributions
 Second Harmonic Generation 

that lead to the particular frequency wn + wm given in the

argument on the left-hand side of the equation are to be retained.

1.3.1 Quantum Mechanical Treatment of the Nonlinear

Susceptibility
More accurate models of the nonlinear optical response are
provided by quantum mechanical calculation [4, 10, 11]. For
example, for the case of usual interest in which the applied and
generated fields are detuned by at least several line widths from
the closest material resonance, the second-order susceptibility
can be expressed as

N mign mnm
j k
mmg
2 PF  mn
c(2)
ijk (w s , wq , w p ) =
, (1.5)
e0  ( wng – ws )(wmg – wp )

where ws = wq + wp and P is the number density of molecules,​

N mign mnm
j k
represents the j-th Cartesian component of the electric-
mmg

P
2 F  mn ( wng – ws )(wmg –moment
dipole wp )
,
matrix element connecting levels n and m, and
wmg is the energy separation of levels m and g divided by .
The symbol PF is the full permutation operator, defined such
that the expression that follows it is to be summed over all
permutations of the frequencies wp, wq, and −ws. The Cartesian
indices are to be permuted along with the related frequencies,
and the final result is to be divided by the number of distinct
permutations of the input frequencies wp and wq. In the
general case in which wp and wq are distinct, this equation thus
expands to six separate terms. Three of these six terms are
illustrated in Fig. 1.2; the other three terms result from a
simple interchange of wp and wq in these figures.

n m g
ωq ωp ωq

m g n
ωp ωp
ωq

g n m
Figure 1.2 Various quantum-mechanical contributions to the second-
order nonlinear optical response.
  Second- and Third-Order Nonlinear Optical Processes

1.3.2  Wave Equation Description of SHG

The intensity of the radiation emitted in the harmonic generation
process can be predicted by means of a propagation calculation
[4]. Consider the wave equation in the form

n2 2 E 2 P ,
NL
2
 K – 2 2 = m0 (1.6)
c t t 2

where m0 denotes the magnetic permeability of free space and

2 2
P ,
NL
– n  E j (z, t)2represents the electric fields in the form of plane waves
2 K = m
c tas follows:
2 2 0
t 2

E j (z, t ) = A j (z )e j j + c .c .,
i (k z – w t )
(1.7)

where j = 1, 2 with w1 = w and w2 = w, respectively, for the

fundamental and second harmonic waves and c.c. stands for
the complex conjugate. Here Aj (z) represents the spatially slowly
varying field amplitude of this wave. The nonlinear polarization
is then given by

P2(z , t ) = P2(z )e i (2k1z – 2wt ) + c .c ., (1.8)

where P2 = P(w2) = e0 c(2) = ​E2​1​​  represents the complex amplitude

of the nonlinear polarization. Upon substituting the expressions
for P2(zand
, t ) =EP1 ,(Ez )2 ein
2
i (2k1 z – 2wt )
the wave + c .c .,Eq. 1.6, a second-order equation
in A2 [1] is obtained. We make the assumption of the slowly
varying envelope approximation (SVEA) which states that the
change in amplitude A2 of the second-harmonic wave is extremely
small over a distance on the order of an optical wavelength. This
approximation results in a simplified first-order equation in
A2. The resulting amplitude of the second-harmonic field after
propagation through a distance L, is given by

2i wc(2) A12 e iDk – 1 , (1.9)

A2(L) =
n2c i DkL
where Dk = 2k1 – k2. Since the_____________
intensity is related to the field
strength according to I = 2n​√0/m0​| A |​2 ​, the intensity of the
generated SHG radiation is determined as
 Coherent Raman Scattering 

m0 2w2  Dk L 
I2 (L) = 2 2
|c(2)|2 I12 L2sinc2 , (1.10)
0 n1 n2c  2 
where sinc(x) = sin(x)/x. The condition Dk = 0 is known as
the condition of perfect phase matching, and is a requirement
for efficient generation of second-harmonic radiation. When
Dk = 0 the last factor in the above equation equals unity and the
intensity of SHG signal scales as the square of the incident
intensity I1.

1.3.3  Symmetry Breaking and SHG Signal in Biological

Imaging
Not all materials are capable of producing a SHG signal. A material
must be noncentrosymmetric over macroscopic distances in
order to produce appreciable radiation at the second-harmonic
frequency [4]. The first biological SHG imaging was reported in
1986 by Freund and coworkers using rat tail tendon [12]. Since
then SHG microscopy has been successfully applied to imaging
subsurface tumor progression [13], collagen distributions and
membrane potential [14–16]. SHG imaging is being developed
as a powerful tool for investigating the changes to the tumor
microenvironment during cancer invasion and metastasis [17].
Polarization-resolved SHG has been applied to yield information
related to the molecular organization of collagen, while SHG
imaging combined with various image analysis techniques
has revealed changes in tissue architecture associated with
connective tissue disorders, musculoskeletal diseases, organ
fibrosis, cardiovascular pathologies, and cancers [18, 19].

1.4  Coherent Raman Scattering

Coherent Raman scattering includes both CARS and SRS and is
related to spontaneous Raman scattering. Theoretical treatments
of the coherent Raman scattering processes can be found both
in the early research papers [20, 21] and in various textbook
accounts [4, 7, 11]. We begin by describing the classical model
of spontaneous Raman scattering. This sets the stage to arrive
at a physical intuitive picture of coherent Raman scattering.
10 Second- and Third-Order Nonlinear Optical Processes

1.4.1 Classical Model of Spontaneous Raman Scattering

As discussed earlier in Section 1.2, the electric field corresponding
to the incident visible or near-IR light beam induces a polarization
in the material given by Eq. 1.4. Since the electrons are bound
to the nuclei, the motion of the nuclei affects the displacement of
the electrons. The purturbative effect of the nuclear modes can
be expressed by connecting the electric dipole moment  a (t )E(t ),
m(t ) =with
  
m(t ) = a(t )Eas
the electronic polarizability (t follows:
),


m(t ) = a (t )E(t ), (1.11)

where
(t ) = a + (aQ )Q
a (t ) + ... (1.12)
0

Here a0 is the electronic polarizability in the absence of either

the nuclear modes or thea (nonlinearities.
t ) = a0 + (aQ )Q(t ) +describes
... the

a(t ) =and
time-dependent nuclear coordinate  ...
a0 + (aQ )Qcorresponds
(t ) + to
the coupling strength between the nuclear and electronic
coordinates.
Assuming the nuclear motion to be that of a classical harmonic
oscillator,

(t ) = 2Q cos (w t + j) = Q [e iwvt + ij + e –iwvt – ij ]

Q (1.13)
0 v 0

Here Q0 is the amplitude of the nuclear motion, wv is the nuclear

resonance frequency, and j is the phase of the nuclear mode
vibration.
Assuming the form for the incident electric field as
E(t) = Ae–iw1t + c.c., where A is the amplitude of the electric
field, the dipole moment is as follows:


m(t ) = a0 Ae –iw1t + A (a / Q ) Q0[e –i (w1 – wv )t + ij + e –i (w1 + wv )t – ij ] + c .c .
(1.14)

It can be seen that the dipole moment oscillates at several

frequencies. Here the first, second and third terms correspond
to the elastically scattered Rayleigh light, the inelastic Stokes-
shifted contribution at ws = w1 – wv and the anti-Stokes-
Another random document with
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latitude, between the 14° 20' meridian of longitude east of
Greenwich (12th degree east of Paris) and the course of the
Upper Nile."

Great Britain,
Papers by Command: Treaty Series, Number 15, 1899.

Of the territorial partition in West Africa which this

important treaty as first signed in 1898 determined, and of
the magnitude of the empire which it conceded to France, a
striking English view was given at the time in the following
article:

"Though we are perfectly satisfied with the agreement, and

though we believe that the country as a whole will be
perfectly satisfied, we do not disguise from ourselves the
fact that under the Convention France receives the full
title-deeds for the most magnificent piece of empire obtained
this century by any European Power,—a dominion which, though
'in partibus infidelium,' is yet within easy reach of both the
western and the southern shores of France. We do not grudge
France the great possession that was finally rounded off and
consolidated on Tuesday; nay, rather we are glad to see it in
her hands, for we want monopoly neither in trade nor in
empire. We see, however, no good in pretending that she has
not obtained the most magnificent opportunity for over-sea
development which has fallen to any Power within recent times.
The best way of understanding the Convention is to realise
what it is that France now possesses in West Africa. Let our
readers look at a map of Africa, and first fix their eyes on
Algiers and Tunis, with their rich soil and splendid harbours
and their remains of an ancient and splendid
civilisation,—Phœnician, Greek, Roman, Christian, and Arab.
Then let them allow their eyes to travel downwards to the
right bank of the greatest river of Africa, the Congo. From
Constantine, with its great memories and its scenery almost
European in charm and splendour, to Brazzaville and Stanley
 Pool, with their tropical vegetation and savage life, there is
a continuous and uninterrupted stretch of French territory. As
they say in our country districts, the French President might now
ride on his own land from Tunis to Loango. The French dominion
of West Africa (as says an official 'communique' to the Paris
Press with very natural exultation) now extends over a space
as great as that from Paris to Moscow. From Algeria to the
Congo, from Senegal to Lake Chad—i. e., almost to the centre
of Africa—stretches this vast tract of French territory. 'At
the present moment,' to quote the words of the 'communique,'
'all our West African colonies—Algeria, Tunis, Senegal,
Futa-Jallon, the Ivory Coast, the Soudan, and the Congo—are in
communication by their respective Hinterlands.'

{335}

"But probably this will not convey much to the ordinary

English reader. Perhaps we can best make him realise the
immensity of the French West African Empire by pointing out
that, with the exception of certain great German and English
and other 'enclaves' the whole of the huge piece of Africa
which bulges out on the map towards the west now belongs to
France. She has all the connecting links, all that does not
specifically belong to some one else, and she cuts off short
the Hinterlands of all the Powers with possessions on the West
African coast. Let us begin at the most western point of the
coast-line of Tripoli in the Mediterranean, and travel round
the coast, marking off all that is not French.

"First, we come to Tunis,—that is in the possession of France

just as Egypt is in our possession. Algiers comes next,—that
is French. Then Morocco. Morocco is at present independent,
but at the back of Morocco all the land, be it desert or
cultivable, is French. Next comes a strip of Spanish coast,
but it goes only a very little way inland, and all the back
country is French. Next come the great French colonies of
Senegambia and Futa-Jallon, with two little colonies embedded
in them, one belonging to us—the Gambia—and the other
belonging to Portugal. Next come our Sierra Leone and
independent Liberia, but here again the Hinterlands are all
French. Next comes the French Ivory Coast colony, then the
British Gold Coast, then German Togoland, and then French
Dahomey. Here again all the Hinterlands beyond, say, four
hundred miles inland, belong, since the signing of the
Convention, to France. After that comes our Colony of Lagos,
then the German Cameroons, and finally the French Congo—the
last French possession in West Africa. Here, too, the
Hinterlands have been cut off by the French, and our Colonies
have been made into 'enclaves' in the mighty French dominion.
It is true that the Niger or Lagos 'enclave' is a very vast
one, and stretches now up to Lake Chad, which becomes
henceforth as international a sheet of water as the Lake of
Constance. Still, it is an 'enclave,' for, as we read the
Convention, he who embarks upon Lake Chad from the British
shore and steers eastward will land on French territory. In
other words, Nigeria cannot now cross Lake Chad and expand
beyond it. We should be glad to hear that this is not the true
reading of the Convention, but we fear it is. We have
travelled, then, round the map of Africa, from Tunis to the
Congo, and found that France is everywhere the chief owner,
—that hers is the great estate, and that the other Powers only
have odd bits of land here and there. We do not say this in
any grumbling spirit, for our odd bit—Nigeria—is very possibly
worth as much as the great estate if Algiers and Tunis are not
counted. We merely wish to make the public understand clearly
that West Africa as a political and geographical expression
has finally passed to France, though we no doubt have carved
one very valuable piece out of it."

The Spectator (London)

June 18, 1898.

Nine months later, when the agreement embodied in the

Declaration of March 21, 1899, had been added to the Original
convention, the "Spectator" explained its effect as follows:

"It will be remembered that last year we and the French agreed
upon a delimitation of 'spheres' in West Africa which extended
as far as Lake Chad. As to the country east of Lake Chad
nothing was said. It was left as a kind of No-man's Land. What
has now been done is to extend the area of the French 'sphere'
eastward beyond Lake Chad till it reaches Darfur and the
Bahr-el-Ghazel. Darfur and the region of the Bahr-el-Ghazel
are declared to be in the English 'sphere.' All the rest of
Northern Central Africa is to become French. France, that is,
is to have the great Mahommedan State of Wadai as well as
Baghirmi and Kanem. In the territory between Lake Chad and the
Nile each Power, however, is to allow the other equality of
treatment in matters of commerce. This will no doubt allow
France to have commercial establishments on the Nile and its
affluents, but it will also allow us to have similar
privileges for trade on the eastern shore of Lake Chad. But as
our system of giving equal trading rights to all foreigners
would in any case have secured commercial rights to France, we
are not in the least hampered by this provision, while the
concession to us of equal rights on the eastern shore of Lake
Chad will improve our position in the face of French Colonial
Protection. …

"The first thing that strikes one in considering the French

possessions in Africa, after this latest addition, is their
vastness. Practically, France will now have all North-Western,
and all Northern, and all North Central Africa, except
Morocco, our West African Colonies, Tripoli, Darfur, and the
Valley of the Nile,—giving that phrase its widest
interpretation, and regarding it as the whole of the country
whence water flows into the Nile. … That, if she plays her
cards properly, she ought to make a success of her African
Empire we cannot doubt, for she starts with immense
advantages. To begin with, she is nearer her African
possessions than any other Power. You can go in a couple of
 days from Marseilles to Algiers and Tunis. Next, in Algiers
and Tunis she has rich colonies with a temperate climate which
may be made the basis for great developments in the way of
railway extension. Lastly, her African possessions are
conterminous, or, at any rate, connected with each other by
land. She owns, that is, Northern Africa, and the rest of the
Powers have only, as it were, enclaves—very large enclaves, no
doubt, in many cases—in her territory. At present this
advantage may not seem very great owing to the vast distances
and the desert character of many of the French Hinterlands,
but if and when France completes her Soudan railways, the
strength of this continuity of territory will become apparent.
But though France has many advantages, it would be foolish to
deny that she has also many serious problems to solve. We
shall perhaps be stating the most dangerous of them when we
say that France now becomes the undisputed master of the great
sect of El Senoussi. There are reported to be over twenty
million followers of El Senoussi in North Africa, and, except
in Tripoli, an these may now be said to be within the French
'sphere of influence.' The Sultanate of Wadai—which, be it
remembered, is a very formidable State, and one which has
never yet come into contact with any European Power—is a
Senoussi State. But the followers of the Senoussi, besides
being numerous, are extremely fanatical. Though practising a
much purer form of Mahommedanism than the Dervishes, they hate
Europeans quite as ardently, and if once their religious zeal
were to be thoroughly roused they would prove most formidable
foes. We do not envy the French their task if they attempt to
conquer Wadai."

The Spectator, March 25, 1899.

{336}

NIGERIA: A. D. 1897:
Massacre of British officials near Benin.
Capture of Benin.
An unarmed expedition from the Niger Coast Protectorate,
going, in January, on a peaceful mission to the King of Benin,
led by Acting Consul-General Phillips, was attacked on the way
and the whole party massacred excepting two, who were wounded,
but who hid themselves in the bush and contrived to make their
way back. The Consul-General had been warned that the king
would not allow the mission to enter Benin, but persisted in
going on. A "punitive expedition" was sent against Benin the
following month, and the town was reached and taken on the
18th, but the king had escaped.

"The city presented the most appalling sight, particularly

around the King's quarters, from which four large main roads
lead to the compounds of the bigger Chiefs, the city being
very scattered. Sacrificial trees in the open spaces still
held the corpses of the latest victims[of 'Ju Ju'
sacrifice]—seven in all were counted—and on every path a
freshly-sacrificed corpse was found lying, apparently placed
there to prevent pursuit. One large open space, 200 to 300
yards in length, was strewn with human bones and bodies in all
stages of decomposition. Within the walls, the sight was, if
possible, more terrible. Seven large sacrifice compounds were
found inclosed by walls 14 to 16 feet high, each 2 to 3 acres
in extent; against the end wall in each, under a roof, was
raised a daïs with an earthen (clay) sacrificial altar about
50 feet long close against the wall on which were placed the
gods to whom sacrifice is made—mostly being carved ivory
tusks, standing upright, mounted at base, in hideously
constructed brass heads. In front of each ivory god was a
small earthen mound on which the victim's forehead would
apparently be placed. The altars were covered with streams of
dried human blood and the stench was too frightful. It would
seem that the populace sat around in these huge compounds
while the Ju Ju priests performed the sacrifices for their
edification. In the various sacrifice compounds were found
open pits filled with human bodies giving forth most trying
 odours. The first night several cases of fainting and sickness
occurred owing to the stench, which was equally bad
everywhere. In one of the pits, partially under other bodies,
was found a victim, still living, who, being rescued, turned
out to be a servant of Mr. Gordon's, one of the members of Mr.
Phillips' ill-fated expedition. At the doors and gates of
houses and compounds were stinking goats and fowls, sacrificed
apparently to prevent the white man entering therein. The
foregoing is but a feeble attempt to describe the horrors of
this most terrible city, which after five days' continuous
fatigue, working with about 1,000 natives, still presents most
appalling and frightful sights. In the outlying parts of the
city the same sights are met and the annual expenditure of
human life in sacrifice must have been enormous. Most of the
wells were also found filled with human bodies."

Great Britain,
Papers by Command: Africa, Number 6, 1897, page 28.

NIGERIA: A. D. 1897:
Subjugation of Fulah slave-raiders.

See (in this volume)

AFRICA: A. D. 1897 (NIGERIA).

NIGERIA: A. D. 1899:
Transfer to the British Crown.

The Royal Niger Company transferred its territories to the

crown in July, 1899, receiving the sum of £865,000. It was
announced to Parliament that three governments would be
formed, named North Nigeria, South Nigeria, and Lagos.

NILE, Barrage and reservoir works on the.

See (in this volume)

EGYPT: A. D. 1898-1901.
NILE VALLEY: The question of possession.

See (in this volume)

EGYPT: A. D. 1898 (SEPTEMBER-NOVEMBER).

NINETEEN HUNDRED, The Universal Jubilee of.

See (in this volume)

PAPACY: A. D. 1900.

----------THE NINETEENTH CENTURY: Start--------

NINETEENTH CENTURY:
The date of the ending of the Century.

Controversy as to whether the Nineteenth Century came to its

end at the ending of the year 1899 or the year 1900 seems
nearly incomprehensible to one who takes the trouble to begin
a counting of years from the beginning of the Christian Era,
and so reaches in his reckoning the fact that the first
century did not end until the 100th year was ended. That seems
to clear all confusion from the question, since the 200th,
300th, 400th, and so on up to the 1900th, must be the closing
years of the successive centuries, just as certainly as the
100th is the last year of the first century. Arithmetically,
there is no question left; but some minds refuse to recognize
the century as a merely arithmetical fact. They see in it an
entity of time with which the counting of years has little to
do. Their somewhat mystical view is set forth in the
following, which we quote from a communication that appeared
in the "New York Times":

"The centurial figures are the symbol, and the only symbol, of
the centuries. Once every hundred years there is a change in
the symbol, and this great secular event is of startling
prominence. What more natural than to bring the century into
 harmony with its only visible mark? What more consonant with
order than to make each group of a hundred years correspond
with a single centennial emblem? Be it noticed that, apart
from the centennial emblems, there is absolutely nothing to
give the centuries any form. The initial figures 18 are time's
standard which the earth carries while it makes 100 trips around
the sun. Then a new standard, 19, is put up. Shall we wait now
a whole year for 1901, at the behest of the abacists? No, we
will not pass over the significant year 1900, which is stamped
with the great secular change, but with cheers we will welcome
it and the new century. The 1900 men, who compose the vast
majority of the people, say to their opponents: 'We freely
admit that the century you have in your mind, the artificial
century, begins in 1901, but the natural century (which we
prefer) begins in 1900.'"

{337}

A consistent application of this view to the defining and

naming of the centuries would seem to require that the years
which carry the initial figures 18 should make up the
Eighteenth, not the Nineteenth Century, and that we should
turn back our centurial nomenclature a whole round.

NINETEENTH CENTURY:
The epoch of a transformation of the world.

In the last years of the Eighteenth Century a new epoch in

history was entered,—an epoch marked by many distinctions, but
most strikingly by what may be called the transformation of
the world. The earlier great ages had been ages of simple
expansion,—of a widening theatre for the leading races,—of a
widening knowledge of the earth and the heavens,—of a widening
range for human thought; but those expansive movements in
civilization led up, at last, to more wonderful processes of
transformation, which were just in their beginning when the
Nineteenth Century dawned. For all the generations of mankind
that had lived before this century, the earth, as a dwelling
place, remained nearly unchanged. They had cleared some
forests from its face, and smoothed some paths; but, in every
substantial feature, the France, for example, of Napoleon was
the unaltered Gaul that Julius Cæsar knew. Everywhere the
material conditions of life were essentially the same for the
man of the Eighteenth Century that they had been for the man
of the First. Then began the amazing work of the brain and
hand of man, by which he has been refashioning and refitting
the planet he inhabits, and making a new world for his
dwelling. As a habitable earth, to-day, it bears no likeness
to the earth on which the first day of this century dawned.
Its distances mean nothing that they formerly did; its
dividing seas and mountains have nothing of their old effect;
its pestilences have lost half their terror; its very storms
are sentinelled and rarely surprise us in our travels or our
work. Netted with steam and electric railways, seamed with
canals, wire-strung with telegraphic and telephonic lines, its
ocean-voyages made holiday excursions, its every-day labors,
of the forge, the plough, the sickle, the spindle, the loom,
the needle, and even of the pen, done with magical deftness by
machines, which its coal mines and its waterfalls lend forces
to move, it is nothing less than a new world that men are
making for themselves, out of that in which they lived at the
beginning of the era of mechanism and electricity and steam.

"Yet these are but outward features of the transformation that

is being wrought in the world. Socially, politically, and
morally, it has been undergoing a deeper change. A growth of
fellow-feeling which began in the last century has been an
increasing growth. It has not ended war, nor the passions that
cause war, but it is rousing an opposition which gathers
strength every year. It has made democratic institutions of
government so common that the few arbitrary governments now
remaining in civilized countries seem disgraceful to the
people who endure them so long. It has broken old yokes of
conquest, and revived the independence of long subjugated
 states. It has swept away unnatural boundary lines, which
separated peoples of kindred language and race. It is pressing
long-neglected questions of right and justice on the attention
of an classes of men, everywhere, and requiring that answers
shall be found.

"And, still, even these are but minor effects of the

prodigious change which the Nineteenth Century has brought
into the experience of mankind." Beyond them all in importance
are the new conceptions of the universe, and of the method of
God's working in it, which can, with no exaggeration, be said
to have imparted a wholly new spirit and quality to the human
mind. By what it learned from Copernicus, it was given a new
standpoint in thinking. By what it learned from Newton, it was
given a new and larger grasp. By what it has learned from
Darwin and Spencer it has been equipped with a new insight,
and looks at even the mystery of life as a problem to be
solved. "If we live in a world that is different from that
which our ancestors knew, it is still more the fact that we
think of a different universe, and feel differently in all our
relations to it."

J. N. Larned,
History of England for the Use of Schools,
page 561.

NINETEENTH CENTURY:
Comparison of the Century with all preceding ages,
as regards man's power over Nature.

"No one, so far as I am aware, has yet pointed out the

altogether exceptional character of our advance in science and
the arts, during the century which is now so near its close.
In order to estimate its full importance and grandeur—more
especially as regards man's increased power over nature, and
the application of that power to the needs of his life to-day,
with unlimited possibilities in the future—we must compare it,
not with any preceding century, or even with the last
millennium, but with the whole historical period,—perhaps even
with the whole period that has elapsed since the stone age."

Such a comparison is made in the following lists of "the great

inventions and discoveries of the two eras":

"Of the Nineteenth Century."

1. Rail ways.
2. Steam-ships.
3. Electric Telegraphs.
4. The Telephone.
5. Lucifer Matches.
6. Gas illumination.
7. Electric lighting.
8. Photography.
9. The Phonograph.
10. Röntgen Rays.
11. Spectrum-analysis.
12. Anæsthetics.
13. Antiseptic Surgery.
14. Conservation of energy.
15. Molecular theory of Gases.
16. Velocity of Light directly measured
and Earth's Rotation experimentally shown.
17. The uses of Dust.
18. Chemistry, definite proportions.
19. Meteors and the Meteoritic Theory.
20. The Glacial Epoch.
21. The Antiquity of Man.
22. Organic Evolution established.
23. Cell theory and Embryology.
24. Germ theory of disease and
the function of the Leucocytes.

"Of all Preceding Ages."

1. The Mariner's Compass.
 2. The Steam Engine.
3. The Telescope.
4. The Barometer and Thermometer.
5. Printing.
6. Arabic numerals.
7. Alphabetical writing.
8. Modern Chemistry founded.
9. Electric science founded.
10. Gravitation established.
11. Kepler's Laws.
12. The Differential Calculus.
13. The circulation of the blood.
14. Light proved to have finite velocity.
15. The development of Geometry.

{338}

"Of course these numbers are not absolute. Either series may
be increased or diminished by taking account of other
discoveries as of equal importance, or by striking out some
which may be considered as below the grade of an important or
epoch-making step in science or civilization. But the
difference between the two lists is so large, that probably no
competent judge would bring them to an equality. Again, it is
noteworthy that nothing like a regular gradation is
perceptible during the last three or four centuries. The
eighteenth century, instead of showing some approximation to
the wealth of discovery in our own age, is less remarkable
than the seventeenth, having only about half the number of
really great advances."

A. R. Wallace,
The Wonderful Century,
chapter 15
(copyright, Dodd, Mead & Company, New York,
quoted with permission).
NINETEENTH CENTURY:
Difference of the Century from preceding ages.

"In the last 100 years the world has seen great wars, great
national and social upheavals, great religious movements,
great economic changes. Literature and art have had their
triumphs and have permanently enriched the intellectual
inheritance of our race. Yet, large as is the space which
subjects like these legitimately fill in our thoughts, much as
they will occupy the future historian, it is not among these
that I seek for the most important and the most fundamental
differences which separate the present from preceding ages.
Rather is this to be found in the cumulative products of
scientific research, to which no other period offers a
precedent or a parallel. No single discovery, it may be, can
be compared in its results to that of Copernicus; no single
discoverer can be compared in genius to Newton; but, in their
total effects, the advances made by the 19th century are not
to be matched. Not only is the surprising increase of
knowledge new, but the use to which it has been put is new
also. The growth of industrial invention is not a fact we are
permitted to forget. We do, however, sometimes forget how much
of it is due to a close connection between theoretic knowledge
and its utilitarian application which, in its degree, is
altogether unexampled in the history of mankind. I suppose
that, at this moment, if we were allowed a vision of the
embryonic forces which are predestined most potently to affect
the future of mankind, we should have to look for them not in
the Legislature, nor in the Press, nor on the platform, nor in
the schemes of practical statesmen, nor the dreams of
political theorists, but in the laboratories of scientific
students whose names are but little in the mouths of men, who
cannot themselves forecast the results of their own labors,
and whose theories could scarcely be understood by those whom
they will chiefly benefit. …

"Marvellous as is the variety and ingenuity of modern

industrial methods, they almost all depend in the last resort
upon our supply of useful power; and our supply of useful
power is principally provided for us by methods which, so far
as I can see, have altered not at all in principle, and
strangely little in detail, since the days of Watt. Coal, as
we all know, is the chief reservoir of energy from which the
world at present draws, and from which we in this country must
always draw; but our main contrivance for utilizing it is the
steam engine, and, by its essential nature, the steam engine
is extravagantly wasteful. So that, when we are told, as if it
was something to be proud of, that this is the age of steam,
we may admit the fact, but can hardly share the satisfaction.
… We have, in truth, been little better than brilliant
spendthrifts. Every new invention seems to throw a new strain
upon the vast but not illimitable, resources of nature. Lord
Kelvin is disquieted about our supply of oxygen; Sir William
Crookes about our supply of nitrates. The problem of our coal
supply is always with us. Sooner or later the stored-up
resources of the world will be exhausted. Humanity, having
used or squandered its capital, will thenceforth have to
depend upon such current income as can be derived from that
diurnal heat of the sun and the rotation of the earth till, in
the sequence of the ages, these also begin to fail. …

"After all, however, it is not necessarily the material and

obvious results of scientific discoveries which are of the
deepest interest. They have affected changes more subtle and
perhaps less obvious which are at least as worthy of our
consideration and are at least as unique in the history of the
civilized world. No century has seen so great a change in our
intellectual apprehension of the world in which we live. Our
whole point of view has changed. The mental framework in which
we arrange the separate facts in the world of men and things
is quite a new framework. The spectacle of the universe
presents itself now in a wholly changed perspective. We not
only see more, but we see differently. The discoveries in
physics and in chemistry, which have borne their share in thus
 re-creating for us the evolution of the past, are in process of
giving us quite new ideas as to the inner nature of that
material whole of which the world's traversing space is but an
insignificant part. Differences of quality once thought ultimate
are constantly being resolved into differences of motion or
configuration. What were once regarded as things are now known
to be movement. … Plausible attempts have been made to reduce
the physical universe, with its infinite variety, its glory of
color and of form, its significance and its sublimity, to one
homogeneous medium in which there are no distinctions to be
discovered but distinction of movement or of stress. And
although no such hypothesis can, I suppose, be yet accepted,
the gropings of physicists after this, or some other not less
audacious unification, must finally, I think, be crowned with
success. The change of view which I have endeavored to
indicate is purely scientific, but its consequences cannot be
confined to science. How will they manifest themselves in
other regions of human activity, in literature, in art, in
religion?"

A. J. Balfour,
The Nineteenth Century
(Address before the University Extension Students
at Cambridge, August 2, 1900).

NINETEENTH CENTURY:
The intellectual and social trend of the Century.

"The two influences which have made the nineteenth century

what it is seem to me to be the scientific spirit and the
democratic spirit. Thus, the nineteenth century, singularly
enough, is the great interpretative century both of nature and
of the past, and at the same time the century of incessant and
uprooting change in all that relates to the current life of
men. It is also the century of national systems of popular
education, and at the same time of nation-great armies; the
century that has done more than any other to scatter men over
 the face of the earth, and to concentrate them in cities; the
century of a universal suffrage that is based upon a belief in
the inherent value of the individual; and the century of the
corporation and the labor union, which in the domain of
capital and of labor threaten to obliterate the individual. …

{339}

"The mind has been active in all fields during this fruitful
century; but, outside of politics, it is to science that we
must look for the thoughts that have shaped all other
thinking. When von Helmholtz was in this country, a few years
ago, he said that modern science was born when men ceased to
summon nature to the support of theories already formed, and
instead began to question nature for her facts, in order that
they might thus discover the laws which these facts reveal. I
do not know that it would be easy to sum up the scientific
method, as the phrase runs, in simpler words. It would not be
correct to say that this process was unknown before the
present century; for there have been individual observers and
students of nature in all ages. … But it is true that only in
this century has this attitude toward nature become the
uniform attitude of men of science. …

"One of the chief results of the scientific method as applied

to nature and the study of the past is the change that it has
wrought in the philosophic conception of nature and of human
society. By the middle of the century, Darwin had given what
has been held to be substantial proof of the theory of the
development of higher forms out of lower in all living things;
and since then, the doctrine of evolution, not as a body of
exact teaching, but as a working theory, has obtained a
mastery over the minds of men which has dominated all their
studies and all their thinking. …

"Every public educational system of our day, broadly speaking,

is the child of the nineteenth century. The educational system
of Germany, which in its results has been of hardly less value
to mankind than to Germany itself, dates from the reconstitution
of the German universities after the battle of Jena. Whatever
system France may have had before the Revolution went down in
the cataclysm that destroyed the ancient regime, so that the
educational system of France also dates from the Napoleonic
period. In the United States, while the seeds of the public
school system may have been planted in the eighteenth, or
perhaps even in the seventeenth century, it has only been in
the nineteenth century, with the development of the country,
that our public school system has grown into what we now see;
while in England, the system of national education, in a
democratic sense, must be dated from 1870. … Out of the growth
of the democratic principle has come the belief that it is
worth while to educate all the children of the state: and out
of the scientific method, which has led to the general
acceptance of the evolutionary theory, has been developed the
advance in educational method which is so marked a feature of
the last decades of the century. …

"Not only has the scientific method furnished a philosophy of

nature and of human life, but, by the great increase in man's
knowledge of natural law to which it has led, it has resulted
in endless inventions, and these, in turn, have changed the
face of the world. … The rapid progress of invention during
the century has been coincident with one far-reaching change
in the habits of society, the importance of which is seldom
recognized. I refer to deposit banking. Of all the agencies
that have effected the world in the nineteenth century, I am
sometimes inclined to think that this is one of the most
influential. If deposit banking may not be said to be the
result of democracy, it certainly may be said that it is in
those countries in which democracy is most dominant that
deposit banking thrives best. … Some one has said that it
would have been of no use to invent the railroad, the
submarine cable, or the telephone at an earlier period of the
world's history, for there would have been no money at command
to make anyone of them available before this modern banking
system had made its appearance. If this be so, then indeed the
part that has been played by deposit banking in the
developments of the century cannot be overestimated.

"During the century the conditions of the world's commerce

have been radically altered. It is not simply that the
steamboat and the locomotive have taken the place of the
sailing-ship and the horse; that the submarine cable has
supplanted the mails; nor even that these agencies have led to
such improvements in banking facilities that foreign commerce
is done, for the most part, for hardly more than a brokerage
upon the transaction. These are merely accidents of the
situation. The fundamental factors have been the opening up of
virgin soil in vast areas to the cultivation of man, and the
discovery of how to create artificial cold, which makes it
possible to transport for long distances produce that only a
few years ago was distinctly classed as perishable. The net
result of these influences has been to produce a world
competition at every point of the globe. …

"Democracy, as a political theory, emphasizes the equality of

men and the equal rights and privileges of all men before the
law. The tendency of it has been, in this country, to develop
in multitudes of men great individuality and self-reliance.
Side by side with this tendency, however, we see the
corporation supplanting the individual capitalist, and the
trade union obliterating the individual laborer, as direct
agents in the work of the world. Strange as this contrast is,
both tendencies must be consistent with democracy, for the
corporation and the trade union flourish most where democracy
is most developed. Indeed, they seem to be successful and
powerful just because democracy pours into them both its vital
strength. …

"The tendency to democracy in politics is unquestionably the

dominant political fact of the century. … Outside of Russia,
 and possibly even there, monarchical government in Europe is
obliged to depend for its support upon the great body of the
nation, instead of upon the power of the great and the noble.
… In the United States, the century, though it began with a
limited suffrage, ends with universal manhood suffrage, and
even with woman suffrage in some of the Western States. …
Undoubtedly, universal suffrage and the large immigration of
people without any experience in self-government have given
form to many of our problems; but I often think there is far
too great a disposition among us to magnify the difficulties
which these conditions present. …
{340}
The fact is, in my judgment, that our problems arise not so
much from universal suffrage as from the effect of the
multiplication table applied to all the problems of life. …
Anyone building a house in the country, when he has dug a well
has solved the problem of his water supply; but to supply
water for a great city calls for the outlay of millions of
dollars, and for the employment of the best engineering talent
in the land. Yet nothing has happened except that the problem
has been magnified. Thus the difficulties created by the
multiplication table are real; so that the very enlargement of
opportunity that democracy has brought with it has faced
democracy with problems far harder than were formerly
presented to any government. …

"To sum up, therefore, I should say that the trend of the
century has been to a great increase in knowledge, which has
been found to be, as of old, the knowledge of good and evil;
that this knowledge has become more and more the property of
all men rather than of a few; that, as a result, the very
increase of opportunity has led to the magnifying of the
problems with which humanity is obliged to deal; and that we
find ourselves, at the end of the century, face to face with
problems of world-wide importance and utmost difficulty, and
with no new means of coping with them other than the patient
education of the masses of men."