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

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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,

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
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Informa Healthcare USA, Inc.
270 Madison Avenue
New York, NY 10016
© 2007 by Informa Healthcare USA, Inc.
Informa Healthcare is an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid‑free paper
10 9 8 7 6 5 4 3 2 1
International Standard Book Number‑10: 0‑8493‑3817‑4 (Hardcover)
International Standard Book Number‑13: 978‑0‑8493‑3817‑5 (Hardcover)
This book contains information obtained from authentic and highly regarded sources. Reprinted material
is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable
efforts have been made to publish reliable data and information, but the author and the publisher cannot
assume responsibility for the validity of all materials or for the consequences of their use.

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

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

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

¨
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

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

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

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

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

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

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

´
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