DERMATOLOGY: CLINICAL & BASIC SCIENCE SERIES BIOENGINEERING OF THE SKIN potx

DERMATOLOGY: CLINICAL & BASIC SCIENCE SERIES
BIOENGINEERING
OF THE SKIN
DK3817_C000a.indd 1 08/22/2006 1:47:27 PM
DERMATOLOGY
CLINICAL & BASIC SCIENCE SERIES
Series Editor
Howard I. Maibach, M.D.
University of California at San Francisco School of Medicine
San Francisco, California, U.S.A.
1. Health Risk Assessment: Dermal and Inhalation Exposure and Absorption
of Toxicants, edited by Rhoda G. M. Wang, James B. Knaack,
and Howard I. Maibach
2. Pigmentation and Pigmentary Disorders,
edited by Norman Levine
and Howard I. Maibach
3. Hand Eczema,
edited by Torkil Menné and Howard I. Maibach
4. Protective Gloves for Occupational Use,
edited by Gunh A. Mellstrom,
Jan E. Wahlberg, and Howard I. Maibach
5. Bioengineering of the Skin (Five Volume Set),
edited by
Howard I. Maibach
6. Bioengineering of the Skin: Water and the Stratum Corneum, Volume I,
edited by Peter Elsner, Enzo Berardesca, and Howard I. Maibach
7. Bioengineering of the Skin: Cutaneous Blood Flow and Erythema,
Volume II, edited by Enzo Berardesca, Peter Elsner,
and Howard I. Maibach
8. Skin Cancer: Mechanisms and Human Relevance,

edited by
Hasan Mukhtar
9. Bioengineering of the Skin: Methods and Instrumentation, Volume III,
edited by Enzo Berardesca, Peter Elsner, Klaus-P. Wilhelm,
and Howard I. Maibach
10. Dermatologic Research Techniques,
edited by Howard I. Maibach
11. The Irritant Contact Dermatitis Syndrome,
edited by Pieter van der Valk,
Pieter Coenrads, and Howard I Maibach
12. Human Papillomavirus Infections in Dermatovenereology,
edited by
Gerd Gross and Geo von Krogh
13. Bioengineering of the Skin: Skin Surface, Imaging, and Analysis, Volume
IV, edited by Klaus-P. Wilhelm, Peter Elsner, Enzo Berardesca,
and Howard I. Maibach
14. Contact Urticaria Syndrome,
edited by Smita Amin, Howard I. Maibach,
and Arto Lahti
15. Skin Reactions to Drugs,
edited by Kirsti Kauppinen, Kristiina Alanko,
Matti Hannuksela, and Howard I. Maibach
16. Dry Skin and Moisturizers: Chemistry and Function,
edited by
Marie Lodén and Howard I. Maibach
17. Dermatologic Botany,
edited by Javier Avalos and Howard I. Maibach
18. Hand Eczema, Second Edition,
edited by Torkil Menné
and Howard I. Maibach

DK3817_C000a.indd 2 08/22/2006 1:47:28 PM
19. Pesticide Dermatoses, edited by Homero Penagos, Michael O’Malley,
and Howard I. Maibach
20. Bioengineering of the Skin: Skin Biomechanics, Volume V, edited by
Peter Elsner, Enzo Berardesca, Klaus-P. Wilhelm, and Howard I. Maibach
21. Nickel and the Skin: Absorption, Immunology, Epidemiology,
and Metallurgy, edited by Jurij J. Hostýnek and Howard I. Maibach
22. The Epidermis in Wound Healing,
edited by David T. Rovee
and Howard I. Maibach
23. Bioengineering of the Skin: Water and the Stratum Corneum, Second
Edition, edited by Joachim W. Fluhr, Peter Elsner, Enzo Berardesca,
and Howard I. Maibach
24. Protective Gloves for Occupational Use, Second Edition,
edited by Anders
Boman, Tuula Estlander, Jan E. Wahlberg, and Howard I. Maibach
25. Latex Intolerance: Basic Science, Epidemiology, and Clinical
Management, edited by Mahbub M. U. Chowdhry and Howard I. Maibach
26. Cutaneous T-Cell Lymphoma: Mycosis Fungoides and Sezary Syndrome,
edited by Herschel S. Zackheim
27. Dry Skin and Moisturizers: Chemistry and Function, Second Edition,
edited by Marie Lodén and Howard I. Maibach
28. Ethnic Skin and Hair, edited by Enzo Berardesca, Jean-Luc Lévêque,
and Howard Maibach
29. Sensitive Skin Syndrome,
edited by Enzo Berardesca, Joachim W. Fluhr,
and Howard I. Maibach
30. Copper and the Skin, edited by Jurij J. Hostýnek, and Howard I. Maibach
31. Bioengineering of the Skin: Skin Imaging and Analysis, Second Edition,
edited by Klaus-P. Wilhelm, Peter Elsner, Enzo Berardesca,

and Howard I. Maibach
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DERMATOLOGY: CLINICAL & BASIC SCIENCE SERIES
BIOENGINEERING
OF THE SKIN
Edited by
Klaus-P. Wilhelm
University of Lübeck
Lübeck, Germany
proDERM Institute for Applied Dermatological Research
Schenefeld/Hamburg, Germany
Peter Elsner
University of Jena
Jena, Germany
Enzo Berardesca
San Gallicano Dermatological Institute
Rome, Italy
Howard I. Maibach
University of California at San Francisco School of Medicine
San Francisco, California, U.S.A.
Skin Imaging and Analysis
Second Edition
New York London
DK3817_C000a.indd 4 08/22/2006 1:47:28 PM
DERMATOLOGY: CLINICAL & BASIC SCIENCE SERIES
BIOENGINEERING
OF THE SKIN
Edited by
Klaus-P. Wilhelm
University of Lübeck

Lübeck, Germany
proDERM Institute for Applied Dermatological Research
Schenefeld/Hamburg, Germany
Peter Elsner
University of Jena
Jena, Germany
Enzo Berardesca
San Gallicano Dermatological Institute
Rome, Italy
Howard I. Maibach
University of California at San Francisco School of Medicine
San Francisco, California, U.S.A.
Skin Imaging and Analysis
Second Edition
New York London
DK3817_C000a.indd 5 08/22/2006 1:47:28 PM
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Bioengineering of the skin : skin imaging and analysis / edited by Klaus‑P. Wilhelm …
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Includes bibliographical references and index.
ISBN‑13: 978‑0‑8493‑3817‑5 (hardcover : alk. paper)
ISBN‑10: 0‑8493‑3817‑4 (hardcover : alk. paper)
1. Epidermis‑‑Imaging. I. Wilhelm, Klaus‑Peter. II. Series: Dermatology (Informa
Healthcare) ; 31.
[DNLM: 1. Epidermis‑‑anatomy & histology. 2. Biomedical Engineering. 3.
Diagnostic Imaging‑‑methods. 4. Skin Diseases‑‑diagnosis. WR 101 B616 2006]
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Preface to the Second Edition

In the eight years since publication of the first edition, enormous progress has been
made in the field of skin imaging and analysis. Because of the broad array of new
methods now available to the research scientist—and more and more to the clini-
cally-oriented dermatologist—we were able to widen the scope of this book from
the skin surface to the entire skin. This is also reflected in the change of the volume
title, Bioengineering of the Skin: Skin Imaging and Analysis.
Hence, this second edition is a major revision of the first edition, with more
than 30 new chapters added.
Those chapters that were already included in the first edition were revised to
reflect up-to-date knowledge. In order to comply with space and cost require-
ments, those chapters dealing with ‘‘older methodology,’’ which might still have
their right and value for many research and/or clinical objectives, but with little
change and development from the time of publication of the first edition could
not be included in this volume.
In a time of ever-increasing speed, budget constraints, and double and triple
obligations, we extend our sincerest thanks to our valued contributors—the
eminent experts in the field of skin imaging and analysis: without the enthusiasm
and commitment to write contributions in their ‘‘leisure time,’’ this book would not
have been possible.
We acknowledge the skillful secretarial assistance of Anna-Karin Jenzen and
Anet Carstensen and thank Barbara Ellen Norwitz, Kari Budyk, Sandra Beberman,
and Dana Bigelow at Informa Healthcare, U.S.A., Inc./CRC Press for committing
to this volume and for accelerating the editorial process. We hope that this new
and completely revised edition will remain the reference book in the rapidly devel-
oping field of skin imaging and analysis and that the format will continue to
provide a perfect introduction to the novice and be the valued reference and stimu-
lation for the expert.
Klaus-P. Wilhelm
Peter Elsner
Enzo Berardesca

Howard I. Maibach
iii

Preface to the First Edition
The fourth volume of our series on Bioengineering of the Skin is devoted to the meth-
ods for skin surface imaging and analysis. Although the skin as the outermost
organ is at least partially visible at the first instant, its fine lines and furrows are
not fully appreciated and quantified by the naked eye.
By continuous research and development of modern instrumentation, analy-
sis and visualization of minute structures of the skin surface are now possible. The
progress in this area has greatly influenced the cosmetic chemist and the basic
researcher alike, which is reflected in this book.
This volume maintains the general outline of the series by focusing on the
instrumentation and the techniques available to image and analyze the skin
surface with special regard to what these instruments do measure and why and
when to use them in skin research and product testing.
We thank our contributors; without their enthusiasm and commitment, this
work would not have been possible.
We acknowledge the skillful secretarial assistance of Helga Schuhbauer and
Paul Petralia, and thank Cindy R. Carelli, and Debbie Didier at CRC Press for
accelerating the editorial process.
We hope that this book will be a perfect introduction to novice researchers
and a valued reference for the expert.
Klaus-P. Wilhelm
Peter Elsner
Enzo Berardesca
Howard I. Maibach
v

Contents

Preface to the Second Edition . . . . iii
Preface to the First Edition . . . . v
Contributors . . . . xvii
1. Anatomy of the Skin Surface . . . . . . . . 1
Claudia El Gammal, Stephan El Gammal, and Albert M. Kligman
Introduction . . . . 1
What Defines How the Skin Surface Appears to
Our Eyes? . . . . 1
References . . . . 13
2. Multimodal Imaging—What Can We Expect? . . . . . . . . . . . . 17
Michael Vogt and Helmut Ermert
Introduction . . . . 17
Skin-Imaging Techniques . . . . 18
Multimodal Skin Imaging . . . . 20
Summary and Conclusions . . . . 27
References . . . . 28
3. Comparative Studies of Scanning Electron Microscopy
and Transmission Electron Microscopy . 31
Masaaki Ito, Fumiko Sakamoto, and Ken Hashimoto
Introduction . . . . 31
Normal Human Skin . . . . 32
Pathological Skin . . . . 40
References . . . . 48
4. Multimodal Imaging of Skin Structures: Imagining
Imaging of the Skin . . 51
Roger Wepf, Tobias Richter, Stefan S. Biel, Holger Schlu
¨
ter,
Frank Fischer, Klaus-Peter Wittern, and Heinrich Hohenberg
Introduction . . . . 51

General Strategy: An ‘‘Information-Transfer Chain’’ . . . . 52
vii
One Biopsy for Multimodal Imaging—the Principle . . . . 55
Lipids—Often Ignored in Biology, Essential for the
Skin Barrier . . . . 57
Application: Reviewing Barrier Morphology and
Dynamics . . . . 58
A New Barrier in Epidermis at the Live-Death Transition . . . . 63
Multimodal Imaging of the Barriers—More Than
One Barrier in Skin . . . . 64
Future Perspective . . . . 65
References . . . . 68
5. Image Analysis of D-Squames, Sebutapes and of
Cyanoacrylate Follicular Biopsies 71
Alessandra Pagnoni, Iqbal Sadiq, Tracy Stoudemayer, and
Albert M. Kligman
Introduction . . . . 71
Cyanoacrylate Follicular Biopsy . . . . 71
Sebutape . . . . 74
D-Squames . . . . 76
References . . . . 79
6. High-Resolution Ultrasound . . . . 83
Michael Vogt and Helmut Ermert
Introduction . . . . 83
Ultrasound Biomicroscopy of Skin . . . . 83
HFUS Scanner . . . . 88
Results . . . . 92
Summary and Discussion . . . . 95
References . . . . 96
7. Magnetic Resonance Imaging of Human Skin In Vivo . . . . . 99

Bernard Querleux, Luc Darrasse, and Jacques Bittoun
Introduction . . . . 99
Review of Magnetic Resonance Imaging of the Skin . . . . 99
Progress in MR Skin Imaging: Spatial Resolution and
Water Behavior in Skin Layers . . . . 103
Perspectives of MR Skin Imaging: Local Microscopy
in Clinical Body Scanners . . . . 105
Summary . . . . 106
References . . . . 108
viii Contents
8. High-Resolution In Vivo Multiphoton
Tomography of Skin . . 111
Karsten Ko
¨
nig
Introduction . . . . 111
State-of-the-Art Skin Imaging Technologies . . . . 112
Principle of Multiphoton Tomography . . . . 113
The Multiphoton Tomograph DermaInspect . . . . 116
Multiphoton Sectioning of Human Skin . . . . 117
In Vivo Fluorescence Lifetime Imaging . . . . 119
Early Detection of Melanoma . . . . 121
In Situ Drug Screening . . . . 122
Laser Safety Aspects . . . . 123
Outlook . . . . 124
References . . . . 124
9. Optical Coherence Tomography . . . . . . 127
Julia Welzel
Introduction . . . . 127
Technique . . . . 127

OCT Studies in Dermatology . . . . 128
Potential of the Technique . . . . 133
Conclusion . . . . 134
References . . . . 134
10. Fringe Projection for In Vivo Topometry 137
So
¨
ren Jaspers
Introduction . . . . 137
Technical Background . . . . 137
In Vivo Topometry . . . . 140
PRIMOS Systems . . . . 142
Parameters . . . . 143
Conclusion . . . . 146
References . . . . 147
11. Confocal Microscopy of Skin In Vitro and Ex Vivo . . . . . . 149
Stefan S. Biel, Roger Wepf, and Sonja Wessel
Introduction . . . . 149
Applications of Confocal Microscopy:
Reflectance Imaging . . . . 154
Applications of Confocal Microscopy:
Fluorescence Imaging . . . . 157
Contents ix
Further Prospects of Confocal Microscopy . . . . 161
Confocal Microscopy in the Context of Other
Microscopic Techniques . . . . 162
References . . . . 163
12. Histometry of the Skin by Means of In Vivo
Confocal Microscopy . . . . . . . . . . 165
Kirsten Sauermann and So

¨
ren Jaspers
Introduction . . . . 165
Vertical Parameters Measured with
the Micronscrew . . . . 165
Distance from Papilla to Capillary . . . . 171
Horizontal Parameters Using Image Analysis . . . . 173
Object Density Parameters . . . . 173
References . . . . 174
13. Two-Photon Microscopy and Confocal Laser
Scanning Microscopy of In Vivo Skin . . . . . . . . . 177
Gerald W. Lucassen and Rob F. M. Hendriks
Introduction . . . . 177
Confocal Laser Scanning Microscopy . . . . 177
Two-Photon Fluorescence Microscopy . . . . 178
Combined TPFM and CLSM . . . . 179
Results . . . . 180
Discussion and Conclusion . . . . 188
References . . . . 189
14. Stereoimaging for Skin Contour Measurement . . . 191
Chilhwan Oh, Min Gi Kim, and Jong Sub Moon
Introduction . . . . 191
Methodological Principles . . . . 192
Clinical Applications . . . . 197
References . . . . 207
15. Development of a Digital Imaging System for Objective
Measurement of Hyperpigmented Spots on the Face . . . . . 209
Kukizo Miyamoto, Hirotsugu Takiwaki, Seiji Arase, and
Greg G. Hillebrand
Introduction . . . . 209

Material and Methods . . . . 209
Results . . . . 214
x Contents
Discussion and Conclusions . . . . 217
References . . . . 219
16. Skin Documentation with Multimodal Imaging
or Integrated Imaging Approaches . . . . 221
Nikiforos Kollias
Introduction . . . . 221
The Interaction of Light with the Skin . . . . 222
Macroimaging of the Skin . . . . 228
Integrated Imaging: Mode—Wavelength . . . . 229
Polarized Light Imaging of Skin . . . . 231
Fluorescence Imaging of the Skin with Excitation in the
Ultraviolet-A Radiation or the Blue . . . . 238
Wavelength Integration . . . . 244
Suggested Reading . . . . 246
17. Combined Raman Spectroscopy and
Confocal Microscopy . . 247
Peter J. Caspers, Gerwin J. Puppels, and Gerald W. Lucassen
Introduction . . . . 247
Raman Spectroscopy . . . . 247
Confocal Scanning Laser Microscopy . . . . 250
Combined Raman and CSLM . . . . 250
Results . . . . 253
Discussion and Conclusions . . . . 257
References . . . . 258
18. Morphometry in Clinical Dermatology . 259
Friedrich A. Bahmer
Introduction . . . . 259

Morphometry: Principles and Applications in 2-D . . . . 260
Stereology: From 2-D to 3-D . . . . 267
Conclusions . . . . 268
References . . . . 269
19. Measurement of Human Hair Growth . 271
Dominique Van Neste
Introduction . . . . 271
Basics About Hair Structure and Function . . . . 271
Hair Photography and Imaging . . . . 272
Conclusion . . . . 283
References . . . . 285
Contents xi
20. Atopic Dermatitis and Other Skin Diseases . . . . . 289
Marie Lode
´
n
Introduction . . . . 289
Dry Skin in Atopic Patients . . . . 289
Psoriatic Plaques . . . . 291
The Ichtyoses . . . . 292
Plaques of Morphea . . . . 293
Melanoma . . . . 293
Microcomedones . . . . 294
Conclusions . . . . 295
References . . . . 295
21. Differentiation Between Benign and Malignant
Skin Tumors by Image Analysis, Neural Networks,
and Other Methods of Machine Learning . . . . . . . 297
Michael Binder, Harald Kittler, Hubert Pehamberger, and
Stephan Dreiseitl

Introduction . . . . 297
Data Acquisition and Preprocessing . . . . 298
Image Segmentation . . . . 298
Feature Extraction . . . . 299
Feature Selection . . . . 299
Value of Clinical Information . . . . 299
Model Building . . . . 300
Logistic Regression . . . . 300
Artificial Neural Networks . . . . 300
Support Vector Machines . . . . 301
Applying Computer Diagnosis on Melanoma and
Pigmented Skin Lesions . . . . 301
Conclusion . . . . 302
References . . . . 303
22. Early Detection of Melanoma by Image Analysis . 305
Stefania Seidenari, Giovanni Pellacani, and Costantino Grana
The ‘‘A’’ of the ABCD Rule: Asymmetry Assessment . . . . 307
The ‘‘B’’ of the ABCD Rule: Border Evaluation . . . . 308
The ‘‘C’’ of the ABCD Rule: Colors . . . . 309
The ‘‘D’’ of the ABCD Rule: Differential Structures . . . . 309
Comparison Between Human and
Computer Assessment . . . . 310
References . . . . 311
xii Contents
23. Visualization of Skin pH . . . . . . . . . . . . 313
Martin J. Behne
Introduction . . . . 313
Established Technique . . . . 314
Alternative Approaches . . . . 314
Imaging Approaches . . . . 315

The Microscopic Approach . . . . 315
Fluorescence Lifetime Imaging Microscopy . . . . 316
Appendix: Web Resources to Orient the Reader . . . . 320
References . . . . 321
24. Visualization of Skin Oxygenation . . . . 325
Markus Stu
¨
cker, Paul Hartmann, Dietrich W. Lu
¨
bbers,
David Harrison, and Peter Altmeyer
Heterogeneity of Skin Oxygenation . . . . 325
Oxygen Uptake from the Atmosphere . . . . 325
Measuring Transcutaneous Oxygen Flux . . . . 326
Imaging of tcpO
2
and tcJO
2
326
Measuring Procedure . . . . 327
Examples for Visualization of Skin Oxygenation . . . . 328
Conclusion . . . . 329
References . . . . 330
25. Capacitance Imaging of the Skin Surface . . . . . . . . . . . . . . 331
Jean-Luc Le
´
ve
ˆ
que
Introduction . . . . 331

Technical Aspects of the Method . . . . 331
Skin Images . . . . 332
Relationship Between SkinChip and Corneometer
Parameters . . . . 333
Skin Surface Hydration Mapping . . . . 333
Skin Microrelief . . . . 335
Conclusion . . . . 336
References . . . . 337
26. Applications of Reflectance Confocal Microscopy
in Clinical Dermatology . . . . . . . . . . . . 339
Cristiane Benvenuto-Andrade, Anna Liza C. Agero, Yogesh G. Patel,
Milind Rajadhyaksha, Allan Halpern, Salvador Gonzalez, and
Susanne Astner
Imaging Parameters for Reflectance-Mode Scanning
Laser Confocal Microscopy . . . . 339
Contents xiii
Confocal Microscopy of Normal Skin . . . . 339
Reflectance Confocal Microscopy Findings of Inflammatory
Skin Conditions . . . . 341
Reflectance Confocal Microscopy Findings of Nonmelanocytic
Skin Lesions . . . . 344
Reflectance Confocal Microscopy of Melanocytic
Skin Lesions . . . . 346
Reflectance Confocal Microscopy as an Adjuvant for
Mohs Micrographic Surgery . . . . 349
Further Developments and Applications of RCM . . . . 349
References . . . . 350
27. Sonography of the Skin in Health and Disease . . 353
Stephan El Gammal, Claudia El Gammal, Peter Altmeyer,
Michael Vogt, and Helmut Ermert

Introduction . . . . 353
Methods and Patients . . . . 356
Results . . . . 358
Discussion . . . . 371
References . . . . 373
28. Noninvasive Imaging in the Evaluation of Cellulite . . . . . . 377
Theresa Callaghan and Klaus-P. Wilhelm
Introduction . . . . 377
Evaluating the Condition–Clinical Considerations . . . . 378
Conclusions . . . . 386
References . . . . 387
29. Effects of Detergents . . . . . . . . . . 391
Minehiro Okuda and Keiichi Kawai
What Is Detergent? . . . . 391
Effects of Detergents on the Skin . . . . 394
References . . . . 401
30. Monitoring Skin Hydration by Near-Infrared Spectroscopy
and Multispectral Imaging . . . . . 403
Shuliang L. Zhang
Introduction . . . . 403
Instrumentation . . . . 405
Clinical Design and Evaluation Methods . . . . 406
Hydration Images and Data Analysis . . . . 408
Results and Discussion . . . . 408
xiv Contents
Conclusion . . . . 414
References . . . . 415
31. Assessment of Anticellulite Efficacy . . . 417
Claudia Rona and Enzo Berardesca
Introduction . . . . 417

Cellulitic Skin Features . . . . 417
Cellulite Stages . . . . 418
Pathogenesis . . . . 418
Noninvasive Techniques to Evaluate Cellulite . . . . 419
Conclusions . . . . 422
References . . . . 422
32. Digital Imaging as an Effective Means of Recording and
Measuring the Visual Signs of Skin Aging . . . . . . . . . . . . . 423
Paul J. Matts, Kukizo Miyamoto, and Greg G. Hillebrand
Introduction . . . . 423
First Principles: Understanding the Interaction of Light
with Aging Skin . . . . 424
Changes in the Expression and Presentation
of Melanin, Hemoglobin, Collagen, and in Surface
Topography with Age . . . . 425
The Effect of Chromophore and Topography Changes in Aging
Skin Upon Perception of Age, Health, and Beauty . . . . 428
The Core Principle of Effective Digital Imaging—
Reproducibility . . . . 429
The Practical Use of Imaging of Aging Skin . . . . 433
State-of-the-Art Color Analysis of Aging Skin—The
Emerging Science of Chromophore Mapping . . . . 435
Conclusion . . . . 443
References . . . . 443
33. Evaluation of Comedogenic Activity by Skin
Fluorescence Imaging Analysis (Skin Analyzing
Fluorescence Imaging Recorder) . . . . . . 447
Andreas Herpens, Silke Schagen, Stefan Scheede, and Boris Kristof
Introduction . . . . 447
Origins of Fluorescence Signals from

Sebaceous Follicles . . . . 448
The Skin Analyzing Fluorescence Imaging Recorder and
Fluorescence Imaging System . . . . 450
Contents xv
Biological Qualification of the SAFIR Fluorescence
Imaging System . . . . 454
Conclusion . . . . 457
References . . . . 458
34. Quantifying Skin Ashing Using
Cross-Polarized Imaging . . . . . . . 459
Robert Velthuizen, Helene Santanastasio, and Srinivasan Krishnan
Introduction . . . . 459
Visual Grading Scale . . . . 459
Digital Image Analysis . . . . 461
Results . . . . 463
Discussion and Conclusions . . . . 466
References . . . . 467
35. Imaging of Pore Size and Sebum Secretion by Sebumtape
During Treatment for Skin Oiliness . . . . . . . . . . . 469
Enzo Berardesca, Claudia Rona, M. B. Finkey, and Yohin Appa
Introduction . . . . 469
Materials and Methods . . . . 469
Results . . . . 471
Discussion . . . . 472
Conclusions . . . . 473
References . . . . 473
36. Utilization of a High-Resolution Digital Imaging System
for the Objective and Quantitative Assessment of
Hyperpigmented Spots on the Face . . . . . . . . . . . . 475
Kukizo Miyamoto, Hirotsugu Takiwaki, Greg G. Hillebrand

and Seiji Arase
Introduction . . . . 475
Materials and Methods . . . . 476
Results . . . . 477
Discussion and Conclusions . . . . 479
References . . . . 482
Index . . . . 483
xvi Contents
Contributors
Anna Liza C. Agero Dermatology Service, Memorial Sloan-Kettering Cancer
Center, New York, New York, U.S.A.
Peter Altmeyer Department of Dermatology, Ruhr-University, and
Dermatological Clinic of the Ruhr-University, St. Josef Hospital, Bochum,
Germany
Yohin Appa Neutrogena Corporation, Los Angeles, California, U.S.A.
Seiji Arase Department of Dermatology, School of Medicine, The University of
Tokushima, Kuramoto-cho, Tokushima, Japan
Susanne Astner Department of Dermatology, Venerology and Allergology,
Charite
´
University Medicine Berlin, Charite
´
platz, Berlin, Germany
Friedrich A. Bahmer Department of Dermatology, Central Hospital, Bremen,
Germany
Martin J. Behne Department of Dermatology and Venerology, University of
Medical Center Hamburg-Eppendorf, University of Hamburg, Germany
Cristiane Benvenuto-Andrade Dermatology Service, Memorial Sloan-Kettering
Cancer Center, New York, New York, U.S.A.
Enzo Berardesca San Gallicano Dermatological Institute, Rome, Italy

Stefan S. Biel Beiersdorf AG, Research Microscopy, Hamburg, Germany
Michael Binder Division of General Dermatology, Department of Dermatology,
Medical University of Vienna, Wahringergurtel, Vienna, Austria
Jacques Bittoun U2R2M UMR8081-CNRS-Universite
´
Paris-Sud,
CIERM-hospital Bicetre, Le Kremlin-Bicetre, France
Theresa Callaghan proDERM Institute for Applied Dermatological Research,
Kiebitzweg, Hamburg, Germany
xvii
Peter J. Caspers Department of General Surgery, Center for Optical
Diagnostics and Therapy, Erasmus MC, and River Diagnostics B.V., Rotterdam,
The Netherlands
Luc Darrasse U2R2M UMR8081-CNRS-Universite
´
Paris-Sud, Orsay, France
Stephan Dreiseitl Department of Software Engineering, Upper Austria
University of Applied Sciences, Upper Austria, Austria
Claudia El Gammal Department of Dermatology, Medical Care Center,
Jung-Stilling Hospital, Siegen, Germany
Stephan El Gammal Dermatological Clinic, Hospital Bethesda, Freudenberg,
Germany
Helmut Ermert Institute of High Frequency Engineering, Ruhr-University
Bochum, Bochum, Germany
M. B. Finkey Neutrogena Corporation, Los Angeles, California, U.S.A.
Frank Fischer Beiersdorf AG, Advanced Development Deo/AP, Hamburg,
Germany
Salvador Gonzalez Dermatology Service, Memorial Sloan-Kettering Cancer
Center, New York, New York, U.S.A.
Costantino Grana Department of Computer Engineering, University of Modena

and Reggio Emilia, Italy
Allan Halpern Dermatology Service, Memorial Sloan-Kettering Cancer Center,
New York, New York, U.S.A.
David Harrison Regional Medical Physics Department, Durham Unit,
University Hospital of North Durham, U.K.
Paul Hartmann Roche Diagnostics GmbH, Graz, Austria
Ken Hashimoto Department of Dermatology, Wayne State University School of
Medicine, Detroit, Michigan, U.S.A.
Rob F. M. Hendriks Philips Research (WA11), Eindhoven, and Lumileds, Best,
The Netherlands
Andreas Herpens Department of Bioengineering, Beiersdorf AG Research,
Hamburg, Germany
Greg G. Hillebrand Procter & Gamble Company, Higashinada-Ku, Kobe,
Japan, and Procter & Gamble Company, Cincinnati, Ohio, U.S.A.
xviii Contributors
Heinrich Hohenberg Beiersdorf AG, Advanced Development Deo/AP,
Hamburg, Germany
Masaaki Ito Department of Dermatology, Niigata University School of
Medicine, Niigata, Japan
So
¨
ren Jaspers Research and Development, Biophysics, Beiersdorf AG,
Hamburg, Germany
Keiichi Kawai Kawai Medical Laboratory for Cutaneous Health, Shimogyo-ku,
Kyoto, Japan
Min Gi Kim Department of Electronics and Information Engineering, Korea
University, Yeonkigun, Choognam, South Korea
Harald Kittler Division of General Dermatology, Department of Dermatology,
Medical University of Vienna, Wahringergurtel, Vienna, Austria
Albert M. Kligman Department of Dermatology, University of Pennsylvania,

Philadelphia, Pennsylvania, U.S.A.
Nikiforos Kollias Methods and Models, Johnson and Johnson Consumer and
Personal Products Worldwide Co., Skillman, New Jersey, U.S.A.
Karsten Ko
¨
nig Fraunhofer Institute of Biomedical Technology (IBMT),
St. Ingbert, and Faculty of Mechatronics and Physics, Saarland University,
Saarbru
¨
cken, Germany
Srinivasan Krishnan Unilever Research and Development, Trumbull,
Connecticut, U.S.A.
Boris Kristof Department of Bioengineering, Beiersdorf AG Research,
Hamburg, Germany
Jean-Luc Le
´
ve
ˆ
que L’Ore
´
al Recherche, Centre Charles Zviak, Clichy, France
Marie Lode
´
n ACO HUD AB, Research & Development, Upplands Va
¨
sby,
Sweden
Gerald W. Lucassen Care & Health Applications, Philips Research,
Eindhoven, The Netherlands
Dietrich W. Lu

¨
bbers Max Planck Institut fu
¨
r Molekulare Physiologie,
Dortmund, Germany
Paul J. Matts Procter & Gamble, Rusham Park Technical Centre, Egham,
Surrey, U.K.
Contributors xix
Kukizo Miyamoto Department of Dermatology, School of Medicine,
The University of Tokushima, Kuramoto-cho, Tokushima, and Research and
Development, Personal Beauty Care, Tokushima, and Procter & Gamble
Company, Higashinada-Ku, Kobe, Japan, and Procter & Gamble Company,
Cincinnati, Ohio, U.S.A.
Jong Sub Moon Department of Electronics and Information Engineering, Korea
University, Yeonkigun, Choognam, South Korea
Chilhwan Oh Department of Electronics and Information Engineering, Korea
University, Yeonkigun, Choognam, South Korea
Minehiro Okuda Kao Corporation, Safety and Microbial Control Research
Center, Tochigi, Japan
Alessandra Pagnoni Pagnoni Consulting, LLC, Yardley, Pennsylvania, U.S.A.
Yogesh G. Patel Dermatology Service, Memorial Sloan-Kettering Cancer Center,
New York, New York, U.S.A.
Hubert Pehamberger Division of General Dermatology, Department of
Dermatology, Medical University of Vienna, Wahringergurtel, Vienna, Austria
Giovanni Pellacani Department of Dermatology, University of Modena and
Reggio Emilia, Italy
Gerwin J. Puppels Department of General Surgery, Center for Optical
Diagnostics and Therapy, Erasmus MC, and River Diagnostics B.V., Rotterdam,
The Netherlands
Bernard Querleux L’Ore

´
al Recherche, Aulnay-sous-bois, France
Milind Rajadhyaksha Dermatology Service, Memorial Sloan-Kettering Cancer
Center, New York, New York, U.S.A.
Tobias Richter Beiersdorf AG, Advanced Development Deo/AP, Hamburg,
Germany
Claudia Rona Department of Dermatology, University of Pavia, Pavia, Italy
Iqbal Sadiq S.K.I.N. Incorporated, Conshohocken, Pennsylvania, U.S.A.
Fumiko Sakamoto Department of Dermatology, Niigata University School of
Medicine, Niigata, Japan
Helene Santanastasio Unilever Research and Development, Trumbull,
Connecticut, U.S.A.
xx Contributors