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Imaging skin: Past, present and future perspectives

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 IMAGING OF THE SKIN
REVIEWS
G ITAL DERMATOL VENEREOL 2010;145:11-28

CA Imaging skin: past, present and future perspectives

DI M. O. VISSCHER

E
M ®
Skin imaging modalities relevant to the range of skin conditions
encountered in clinical settings are described with respect to the
information provided, advantages and limitations, current sta-
The Skin Sciences Institute
Division of Neonatology and Pulmonary Biology
Cincinnati Children’s Hospital Medical Center

A
tus and indications for further development. The methods use the and Department of Pediatrics

V T
interaction of energy with the skin, penetrating to various depths
in the stratum corneum, epidermis, dermis and subcutaneous lay-

H
ers. They include a detection system such as the retina, film or a
digital array, and a processing system to deconstruct, analyze and
University of Cincinnati College of Medicine
Cincinnati, OH, USA

R
interpret the information. Similarly, the areas of interest, or tar-

G
gets, have common features. The skin conditions deviate from the

E I
ideal or normal state with respect to skin integrity and function.
The deviations include evidence of barrier disruption, inflam-
mation, dispigmentation, and vascular change. The user of skin
tered in the clinical setting in comparison to normal,
healthy skin and, thereby, to address readers from the
health care, clinical, research and industrial settings.

IN YR
imaging is often interested in the extent and severity of disease. Skin imaging modalities will be described with respect
Part of the task in skin imaging is to establish the criteria for the to the goals, methodologies, current status, advantages
normal condition. The review encompasses the past, present and
future of visual assessment, photographic image collection, spec-
and limitations, i.e., opportunities for further devel-
opment. Practical considerations for implementing

M P
trophotometric techniques, noninvasive histology, and three
dimensional scanning. The analytical techniques for processing skin imaging techniques in clinical and research set-
and extracting specific parameters that inform about the under- tings will be presented. A further objective is to show

O
lying biological status are presented. the commonality among imaging modalities, i.e., to
Key words: Skin diseases - Imaging, three-dimensional - Der- inform the user about the biological response to a stres-
sor under specified conditions and without artifacts

C
moscopy.
T his paper will review imaging of the skin. Con-
ceptually, imaging will be broadly defined as “the
creation of visual representations of objects for the
purpose of data collection or medical diagnosis using
any of a variety of usually computerized techniques”.1
The goal is to present imaging in a way that is relevant
to the range of skin “conditions” typically encoun-
Corresponding author: M. O. Visscher, PhD, The Skin Sciences Insti-
tute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave-
nue, Cincinnati, OH 45229 USA. E-mail: Marty.Visscher@cchmc.org
from information processing. It is, however, beyond the
scope to review the plethora of methods in detail.
Skin imaging has been comprehensively reviewed,
particularly with respect to the advantages it may offer
for clinical dermatology. Dr. Perednia discussed pho-
tography and image analysis, ultrasound, magnetic
resonance imaging (MRI) methods and three-dimen-
sional reconstruction for non-visible light imaging,
cataloging of patient histories, education, communi-
cation, evaluating changes over time in comparison
to standard visual methods, and diagnosis.2 He dis-
cussed the advantages of these quantitative objective
measures in terms of increased clinician efficiency for

Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 11

VISSCHER
A
IC
E D
M ®
Figure 1.—The electromagnetic spectrum.
A T
overcoming the limitations posed by recall and objec-
tivity. In 2004, Rallan and Harland reviewed the top-
V
ic with a provocative title “Skin imaging: is it clinically
R H
useful?”.3 The detailed review of imaging methods
emphasizes surface textural assessment and subsur-
G
face techniques (e.g., dermoscopy) to characterize
E I
lesions and classify moles. In vivo microscopic meth-
ods were discussed in terms of future potential as sub-
stitutes for the invasive skin biopsy. They cautioned
IN YR
about the limited predictive value and the potential
for misinterpretation. The specialty of plastic surgery
has relied on photography to document patient char-
acteristics, for treatment planning, and to evaluate sur-
M P
gical outcomes for over fifty years.4 Galdino et al.
compared the newer high resolution cameras and found
O
variability in quality and contrast among specific
brands. To overcome this potential limitation and to
facilitate effective comparison of images taken at dif-
C
ferent times, the lighting, collection and image pro-
cessing procedures must be standardized.4
A search of “skin imaging” in PubMed today pro-
duces about 9800 citations, more than 900 of which
appeared in the past twelve months. The topic is pre-
sented across the range of medical specialties, e.g., nurs-
ing, radiology, surgery, perinatal medicine, dermatology,
emergency medicine and biomedical engineering. The
specific methods include “traditional” imaging such as
photography as well as “internal” methods including
magnetic resonance imaging, interventional radiology
and in vivo confocal microscopy. Generally, the pur-
poses of “imaging skin” are to: quantify clinical judg-
12 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
IMAGING SKIN
ment, determine the stage of disease progression, estab-
lish the efficacy of a treatment, select an appropriate
treatment, generate evidence for clinical practice, iden-
tify the biological changes that define the disease state,
determine the physical and chemical composition, and
relate physiological changes to biomarkers (or labora-
tory measures) to assess the mechanism of action. Use
of skin imaging provides the opportunity to relate clin-
ical judgment to patient/client response and to estab-
lish the relationship between patient expectations and
treatment efficacy as judged by clinicians.
Skin: energy interactions
Methods of imaging skin use energy of various
wavelengths in the electromagnetic spectrum to extract
information and determine specific features. Energies
ranging from the low frequency (longer wavelengths)
of 7 MHz to the high frequency (shorter wavelengths)
of x-radiation (~1013 MHz) have been used to evalu-
ate and collect information from the skin (Figure 1). For
example, MRI uses radio frequency energy coupled
with a magnetic field to evaluate subsurface features
of skin, such as subcutaneous fat. Ultrasound methods
use the interaction of high frequency sound waves to
characterize skin. Devices range from 7 MHz (wave-
length ~200 micrometers) for deep tissues to 20 MHz
frequencies (wavelength ~70 micrometers) for evalu-
ating dermal thickness and to characterize the three
dimensional structure. The stratum corneum (SC) and
upper epidermis can be examined with 50 MHz (~30
micrometers) probes. Dual energy absorptiometry
(DEXA scan) uses low exposure to two different X-ray
energy levels to quantify fat and muscle beneath the
skin surface. Optical coherence tomography obtains 3D
images by using wavelength in the near infrared region
and relies on optical scattering in the tissue to gener-
ate 3D images. Resolution is at the micrometer level.
In vivo confocal Raman spectroscopy is a relatively
new technique that uses inelastic light scattering and
a specific wavelength of laser light to determine the
concentration and depth of molecular species in the
upper epidermis.5 The wavelengths of the scattered
light are slightly longer than visible light. The wave-
length and shape provide a molecular “fingerprint”
that can be assigned to a specific compound. Many
skin imaging methods use the “optical” spectrum,
defined as wavelengths from 250 nm (ultraviolet) to
3 000 nm (infrared), to discern features of interest.6
February 2010
IMAGING SKIN
A
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DI
Figure 2.—Human color perception.
E
Human color perception and visual skin imaging
M ®
One may assert that the most important skin imag-
ing method is human color vision. Visual methods are
A
T
the foundation of clinical care and the “gold standard”
for skin color assessment.7 Clinical judgments depend
V
H
upon perception of the skin surface.8 Human beings use
skin coloration to infer physiological health status.9
R
Subjects viewed high resolution images of human
G
faces and were instructed to adjust the red color to
E I
achieve a “healthy appearance”. All subjects increased
the red color, regardless of the inherent pigmentation,
IN YR
but subjects with dark skin themselves increased the red
component of dark skin photos more than for lighter
skin.9 Visual responses to facial image sets, standard-
ized for shape and surface features, were recorded
M P
with eye-tracking methods. Images with more uni-
form skin coloration drew more attention and were
perceived to be younger than those with greater color
O
variability.10 The distribution of skin color on the face
has been associated with the perception of overall
C
health.11
Humans perceive color when three types of cone
cells on the retina receive and mediate light. Long (L)
cones have peak absorption at 564-580 nm (range 500-
700), medium (M) cones at 534-545 nm (450-630),
and short (S) cones at 420-440 nm (400-500), corre-
sponding roughly to the red, green and blue regions of
the color spectrum (Figure 1).12, 13 A color of 600 nm
would produce a response in both the L and M cones.
Processing of incoming light occurs in the optic nerves
and the visual cortex of the occipital lobe. The red,
green, blue (RGB) tristimulus color space is an addi-
tive model based on the chromaticities (quantity of
Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
VISSCHER
Incident energy
Reflection
Fluorescence
Stratum corneum
(10 mm)
Epidermis
(100 mm)
Dermis Scattering Absorption
(3 mm)
Dermal capillaries
Melanocytes
Melanosomes,
Melanin transfer
Figure 3.—Energy interactions with skin.
color specified by dominant wavelength) of red, green,
and blue additive primaries (Figure 2). It is used in
digital cameras, monitors, televisions, image pro-
cessing programs, etc.14
Perceived skin color arises when visible light inter-
acts with components within the skin including the
constitutive pigments melanins (yellow to brown),
oxygenated hemoglobin (red), deoxyhemoglobin (blue-
purple), bilirubin (yellow) and carotene (yellow).15
The observed skin color arises from the interplay of
light with components of the stratum corneum, epi-
dermis and dermis. It is determined by diffuse reflec-
tion and scattering and absorption of light inside the
skin.15, 16 Of the total incident light contacting the
skin.6 The remainder is transmitted, absorbed or scat-
tered by structural and chemical elements within the
skin corneum, epidermis, dermis and subcutaneous
tissues, as shown in Figure 3. The stratum corneum
transmits light, the epidermis and dermis absorb light
due to the presence of melanin and hemoglobin and
scatter some light, and the subcutaneous fat scatters
light back.17 Melanin is synthesized by the melanocytes
(dendritic cell) in the basal layer of the epidermis and
transferred to the keratinocytes throughout the epi-
dermis.18 Oxygenated blood in the dermal capillaries
and vascular plexis and deoxygenated blood (blue-
purple) in the dermal venules contribute to skin color.19
The yellow pigment carotene is in the epidermis. Biliru-
bin (yellow) is in the epidermis due to result of pre-
cipitation in phospholipid membranes and leakage as
a complex with albumin into extravascular regions.20
13
VISSCHER
TABLE I.—Eczema Area and Severity Index (ESAI).
Body Site Region Score
Head/Neck (E + I + Ex + L) × Area × 0.1
Upper limbs (E + I + Ex + L) × Area × 0.2
Trunk (E + I + Ex + L) × Area × 0.3
(E + I + Ex + L) × Area × 0.4
A
Lower limbs
Total EASI Score Sum of Regions
IC
E = erythema, I = induration/palpulation, Ex = excoriation, L = lichenification,
are each evaluated on a severity scale of 0 – 3, where 0 = none, 1 = slight, 2 = mode-
rate, and 3 = severe.
E D
Visual skin imaging methods
Visual skin methods commonly use descriptors
M ®
such as slight, mild, moderate, severe to indicate
severity of damage, e.g., inflammation and erythema,
and area (percent) of involvement relative to nearby
A
areas of normal.21, 22 One advantage is that they are
V HT
clinically relevant and rely on experience with devi-
ations from the “normal” skin features. Examples of
the clinical conditions and the evaluation methods
are as follows.
R
G
E I
Inflammation
Skin inflammation is a common feature of many
IN YR
conditions, including irritant contact dermatitis, aller-
gic contact dermatitis, acne, psoriasis, eczema, pres-
sure ulcers and wounds. Minor abrasions, scratches
and fissures are characterized by erythema (redness),
M P
edema, exudate, and minor bleeding, usually sur-
rounded by areas of normal, non-damaged skin. The
extent of injury is typically determined with visual
O
scoring methods based on severity (e.g., slight, mild,
moderate, severe) and area (percent) of tissue damage.
C
Erythema (abnormal redness from capillary dilation
and increased blood flow) is the visible indicator of
inflammation, infection or irritation.23 The degree of
erythema is typically assessed with somewhat sub-
jective methods.24-26 Inherent skin pigmentation (i.e.,
brown, yellow, red colors due to melanin) influences
the interpretation of visual erythema. Changes in
blood, e.g., pooling in the tissues, affects the appear-
ance of skin pigmentation.27 Ben-Gashir reported that
skin pigmentation, particularly in dark skinned
patients, influenced the assessment of erythema in
atopic dermatitis and cautioned that the severity could
be underestimated. 28 The evaluation of the non-
14 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
IMAGING SKIN
blanchable erythema of stage I pressure ulcers is a
recognized limitation of the current staging system.29
The visually based pressure ulcer scale for healing
(PUSH) has been developed for the determination of
healing status and is the method recommended by the
National Pressure Ulcer Advisory Panel.30 However,
only a 43% agreement between the PUSH results and
typical nursing assessments of healing (i.e., deterio-
rating, unchanged, improved) was observed, indicat-
ing that the development/implementation of an accu-
rate system is essential to improved clinical out-
comes.31
Atopic dermatitis and psoriasis
The need for an evaluation system that would effec-
tively measure response to treatment over a wide range
of presentations and that would be consistent, valid,
reliable, simple to use in a clinical setting motivated the
development of the eczema area and severity index
(EASI).32 It is based on two components of skin dis-
ease, total area of involvement and disease intensity
measured as erythema (E), induration/papulation (I),
excoriation (Ex), and lichenification (L) The common
eczema features of scaling, xerosis, oozing, crusting
and pruritus were not included in the schema because
they are not essential markers of the disease and/or
are subjective. Each attribute is scored from 0 to 3
(0=none, 1=slight, 2=moderate, 3=severe, with half
grade increments as needed). The area of involvement
is estimated and assigned a number from 0-6, where
0≤10%, 2≤10-29%, 3≤30-49%, 4≤50-69%, 5≤70-89%,
and 6≥90-100%. The total EASI score is derived from
the severity and area values over the entire body (Table
I). The EASI is based on the scale for judging psoria-
sis.33
The European Task Force on Atopic Dermatitis for-
mulated a similar method for younger patients.34 Area
(A) is estimated using the rule of nines and severity (B)
of erythema, edema/population, oozing/crust, exco-
riation, and lichenification are each rated from 0 to 3
(0 = none, 1=slight, 2=moderate, 3=severe). Pruritus
and sleep loss (C) are reported by caregivers on 0-10
scales. The score (SCORAD) is calculated as follows:
A/5+7B/2+C. There was good agreement between
scores by expert and non-expert evaluators indicating
applicability for use by a variety of personnel.34 The
SCORAD items of intensity, area and symptoms (pru-
ritus, sleep) were positively correlated to disease mark-
ers serum eosinophil cationic protein and urinary
February 2010
IMAGING SKIN VISSCHER

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VA T
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E I
IN YR
M P
Figure 4.—Diaper Dermatitis Grading Scale.

O
eosinophil protein X among infants and children.35
Area of involvement has also been determined by

C
shading involved regions on body diagrams and ana-
lyzing area with software (Scion Image beta 4.02,
National Institutes of Health: www.scioncorp.com/
frames/fr_scion_products.htm) to create the Objec-
tive Severity Assessment of Atopic Dermatitis Score
(OSAADS).36 It incorporates values of skin barrier
function, i.e., transepidermal water loss and skin hydra-
tion, measured as differences from normal values, by
the affected area at each severity level and is an effec-
tive scheme for assessment of adult atopic patients.37
In the adults, OSAADS scores were generally corre-
lated (r=0.56, P<0.05) for interleukin-16 as a marker
of atopic disease intensity.
Infant skin
Methods have been devised for evaluating extent
and severity of irritant diaper dermatitis. To address the
skin type heterogeneity, each region (perineal, geni-
tal, buttocks, and intertriginous) is assessed for ery-
thema and rash using standardized scales (7-point 0-
3, 0.5 grade increments) with scores based on sur-
face area of coverage and intensity of the compro-
mise.38 A visually based version has been developed
for use in clinical and research settings to monitor
treatment effects by noting the area of involvement (%
area covered) and severity of damage (faint erythema,
definite redness, intense redness, rash, bleeding, etc)
(Figure 4).39

Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 15

VISSCHER
TABLE II.—Global Severity Assessment Scale for Acne.
Grade Classification Attributes
0 None No inflammatory lesions
1 Only an occasional small inflammatory lesion
A
2 Mild Few scattered lesions, mild erythema on less
than half of the face
C
3 Moderate number of inflammatory lesions,
increasing erythema, over wide area of face
I
4 Moderate Moderate number of inflammatory lesions,
some large, increasing erythema, over wide
D
area of face
5 Papules and pustules with larger inflamed
E
lesions, pronounced erythema, covers much of
face
6 Severe Large papules and pustules, pronounced
M ®
erythema, covers most of face
A
Acne
V T
A visual global severity assessment scale has been
developed for acne and later refined (Table II).40 This
H
method incorporates the extent of disease by incor-
ER
porating the number of lesions, their size and the extent
IG
of inflammation. Representative photographs are often
used during evaluation to provide reminders of the
grades and severity. In one study, a grade change of ≥1
IN YR
was considered to be clinically meaningful.41 As with
other visual scales, training and inter-rater calibration
is necessary for comparison of results across multi-
ple clinical sites.
Wounds
M P
O
Wounds are evaluated for severity, depth, healing,
etc., by a wide range of health care specialties (e.g.,
C
certified wound ostomy and continence nurses, sur-
geons, dermatologists, general physicians, and nurs-
es) because wounds transcend underlying disease
processes. The Pressure Ulcer Scale for Healing
(PUSH) is a comprehensive visual assessment scheme
for pressure ulcers that includes sub-scores of wound
size, exdudate amount and stage of healing by tissue
type (epithelial, granulation, slough, necrotic) (Figure
5).42 Dermatitis secondary to radiation therapy has
been evaluated by several visual methods to encom-
pass skin damage (erythema, erosion) and responses that
indicate healing (desquamation, hyperpigmentation).43,
44 One example is shown in Table III.
16 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
IMAGING SKIN
Scars
Deep tissue injuries such as burns, wounds and sur-
gical incisions can result in the formation of hyper-
trophic scars that are then treated to improve function
and aesthetic appearance of the effected area. The Van-
couver Scar Scale (VSS) is used to evaluate four char-
acteristics of burn scars following injury or recon-
structive surgery by assigning numerical values to the
four parameters of vascularity, pigmentation, height and
pliability (Table IV).45 Vascularity is inferred from
color descriptors, pigmentation from color due to
melanin, height relative to the surrounding tissue, and
pliability by palpation. Pliability reflects a mechanical
tissue property. Since the assessment requires tactile
interaction with the skin, it does not fit the traditional
criteria for visual assessment.
Imaging skin: instrumental methods
Visual skin assessment based on relevant features of
the underlying biology is a mainstay for effective clin-
ical care. However, the methods often are limited.
There are frequently no “universal standards” for nor-
mal skin integrity and color making them difficult to
implement uniformly across institutions and geogra-
phies. Drawbacks also include low reproducibility,
variation among skilled, experienced observers and
low reliability.24, 25 The accuracy of visual methods is
significantly impacted by the inherent skin pigmenta-
tion, varying from very light (Caucasian) to very dark
(African). Erythema is difficult to assess in the dark-
er skin due to masking by the red, yellow and brown
pigments. This tissue damage may be underdeter-
mined. Of particular importance is the determination
of skin compromise in dark skinned patients who risk
more severe injury and for whom skin pigmentation
interferes with detection of erythema.46, 47 In another
example, visual evaluation of neonatal jaundice under-
estimated serum bilirubin in 17-40% and over esti-
mated levels in 5-36% in a sample of 517 infants.48
In examining the need and utility of objective quan-
titative measurements of skin condition, disease process
and response to treatment, consider the report of Ben-
deck and Jacobe who provide the criteria for a good
outcome measure.49 They assert that measurements
need to 1) determine whether a real change has
occurred as a result of an intervention; 2) accurately
show that a condition is different from the normal; 3)
February 2010
IMAGING SKIN VISSCHER

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E I
IN YR
M P
Figure 5.—The Pressure Ulcer Scale for Healing (PUSH).

CO
be valid as defined by correlating to the gold standard
of visual clinical assessment, standard; 4) be repro-
ducible; and 5) be feasible.49 The following skin imag-
ining methods are reviewed with these criteria in mind.
Photography and digital imaging
Recent estimates suggest that 85% of dermatolo-
gists use photography at least some of the time and
20% take photographs as a standard procedure for all
patients.50 Photographic and imaging techniques have
been developed to improve the objectivity and quan-
tify the particular skin features (e.g., erythema, dispig-
mentation, abrasion).17, 51, 52 Under standardized con-
ditions (lighting, focal length, white balance and col-
or correction), photographs serve as a permanent clin-
ical records and can be evaluated by multiple exam-
iners. Standardization of image collection (controlled
lighting, white balance, color correction) facilitates
comparison of images taken at different times. Pre
versus post-treatment comparisons can occur in real
time. They have been used to objectively assess pho-
toaging, blanching, skin atrophy, wounds, burns,
lesions, and disease (e.g., psoriasis).25, 26, 52-55
For image capture (photography) and analysis to be
relevant, practical, feasible and useful, the informa-
tion must at some point be related back to the live clin-

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VISSCHER IMAGING SKIN

TABLE III.—Radiation Dermatitis Severity Assessment. TABLE IV.—Vancouver Scar Scale.

Characteristic Score Characteristic Score

Induration 0 normal Vascularity 0 normal

1 slight 1 pink
2 moderate 2 red

A
3 severe 3 purple
Desquamation 0 normal Pigmentation 0 normal
1 slight 1 hypopigmentation

C
2 moderate 2 mixed pigmentation

I
3 severe 3 hyperpigmentation
Erythema 0 normal Height 0 flat
1 slight 1 less than 2 mm

D
2 moderate 2 2 to 5 mm
3 severe 3 more than 5 mm

E
Hyperpigmentation 0 normal Pliability 0 normal
1 slight 1 supple
2 moderate 2 yielding
3 severe 3 firm

M ®
4 ropes
Excoriation 0 normal 5 contracture
1 slight
2 moderate
3 severe Total Sum of individual scales

A
Maximum = 14
Total

V HT Maximum = 15

for grades of slight and moderate erythema, but not

R
ical examination. The perception of color depends for intense erythematic lesions when visual erythema

G
upon the features of the illuminating light (energy was high. They suggested that other symptoms accom-

E I
used to collect information), the traits of the observer panying the erythema (i.e. edema, infiltration, vesi-
(eye physiology, interpretation), and the interaction cles, etc) masked the actual red color52. Oduncu, et

IN YR
of light with the object.56 Given this, colors repre-
sented in the RGB model described above cannot be
easily related to the way the human eye perceives col-
or. To address this, the values in RGB were used to
al., used the hue, saturation and intensity (HIS) color
model measurements for analysis of chronic wounds.55
The amount of slough was quantified and compared
with expert visual inspection scores. The overall cor-

M P
generate the CIE 1976 L* a* b* (CIELAB) color val- relation between the methods was excellent for lower
ues. As a result of the conversion, colors are in a uni- grades but moderate overall.55
form three-dimensional space where L* is the light- We evaluated repetitive hand hygiene procedures

O
ness-darkness (L* of 100=white and L* of 0=black),
a* is red-green (positive to negative, respectively) and

C
b* is yellow-blue (positive to negative) (Figure 6).13,
57 Values of CIE L*, a*, and b* were determined from

reflectance spectroscopy measurements of adult fore-

arm skin over 400-700 nm and color differences were
observed across the population. As a result, the L*a*b*
system was proposed for the objective clinical assess-
ment of human skin.56
Setaro et al. used color markers on the skin to cor-
rect for variations in lighting and analysis of RGB
images to quantify erythema in patients (multicenter,
N=348) after esthetic treatments (e.g., chemical peel,
laser resurfacing).52 They found a good correlation
between digital image analysis (DIA) and visual scores
in health care workers found the hand skin to be appre-
ciably compromised (dryness and erythema) regardless
of season.58 Erythema was particularly difficulty to
assess, partly due to the extent of epidermal barrier
compromise and the regional heterogeneity across the
hands. We determine the effects of insults and treat-
ments. We acquired high resolution images (RBG for-
mat) under controlled lighting conditions and ana-
lyzed them to objectively quantify skin erythema.
White balance was corrected and tonal value (bright-
ness) enhanced to improve visual image. White point
was selected and remapped and tonal information
images were compressed (4:1) in the lossless (TIFF)
format to retain all detail of the original image. To
amplify subtle color differences and remove the con-

18 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA February 2010

IMAGING SKIN VISSCHER

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Figure 6.—RGB Color Model and CIE L*a*b* Color space.

E I
founding effects of dependent color components, the
images were transformed into luminance and chromi-
A significant correlation between color changes by
DIA and laser Doppler values suggested an association

IN YR
nance representation by conversion to L*a*b* color
and separating them into three distinct images (L, a*,
and b*).55, 60, 61 The enhanced a* component image
was saved as a grayscale image and used for analysis
between erythema and blood flow.25 Nystrom et al.
used near-infrared (NIR) spectroscopy, laser Doppler
perfusion imaging (LDPI), and digital photography
to measure erythema of breast cancer patients (N=28)

M P
of redness. The a* component was selected since it is
correlated with the visual evaluation of skin erythema.62
Means (µ) and standard deviations (σ) from the a*
receiving different doses of radiation.26 From image
analysis, the authors proposed a skin redness index
that increased with higher radiation. All methods cor-

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channel histogram data were calculated with ImageJ
(National Institutes of Health, Washington, USA) to

C
generate µ+σ. Pixels with redness higher than µ+σ, to
188, were considered to represent excess erythema.63
This method has been used to examine treatment effects
for irritant hand dermatitis.64
Digital image analysis (DIA) has been compared
with other skin color methods.25, 26 Mattsson et al.
obtained clinical photographs from subjects (N=12)
exposed to a mild experimental thermal injury and
used normalized RGB and for image analysis.25 Ery-
thema by both methods was most pronounced during
the first hour postburn then gradually decreased while
skin perfusion (measured with laser Doppler meth-
ods) peaked at 30 minutes and continuously decreased.
related to varying degrees.26
Skin conditions such as wounds, burns and pressure
ulcers are very heterogeneous over the affected area
with respect to severity, depth and stages of compromise
or healing. Image analysis methods that use thresh-
olds, to determine percent area of involvement over
the mean or compared to a normal skin site are useful.
Segmentation algorithms have been developed for ana-
lyzing complex wounds such as pressure ulcers.65 Fig-
ure 7 shows a pressure ulcer with varying stages of
injury before and after computer segmentation. The
relevant features are extracted and classified by human
experts. Image processing routines (e.g., edge detection)
are applied and the resultant segmented images used to
“train” the computer for routine analysis.65

Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 19

VISSCHER IMAGING SKIN

CA
I
Figure 7.—Wound (pressure ulcer) with varying stages of severity befo-
re (left) and after image segmentation (right). From Kosmopoulos DI,
Tzevelekou FL. Automated pressure ulcer lesion diagnosis for telemedi-

D
cine systems.65

E
Visual perception system method
Skin features can be evaluated from pairs of high res-

M ®
olution images, provided they were taken under con-
trolled lighting conditions, at a fixed distance from
the subject, with standardization for subject position-
Figure 8.—Skin absorption spectra.

A T
ing and color corrected as describe above. The method
depends upon accurate repositioning so the judges

V
cannot use subtle differences to infer time or treat-
method, “judges” first view single images to obtain a
frame of reference for the range of severity of a given

H
ment effects. Image pairs are presented at random

R
using an algorithm and viewed on a high resolution

G
monitor (e.g., flat screen, 12×16 inches). Judges are
attribute, e.g., pigmentation, erythema, scaling. Pairs
of images are then presented to allow observers to
detect small differences in images.68 In the two-alter-

E I
blinded with respect to both order and pair. Images native forced-choice (TAFC) method, judges score
can be compared to specific attributes (e.g., erythe- each image within a pair. The method assumes that
the image with the higher score has the more severe

IN YR
ma, lightness, edema, dryness). The high resolution
allows “magnification” photograph after resolution to
examine specific regions and/or detail not easily
observed with the naked eye. Judges use a fixed line on
condition.68 Randomized pairs of varying differences
in severity are evaluated to determine the threshold of
incremental discrimination (i.e. grade 1 vs. 7, 6-incre-
ment difference). Pairs of identical images serve as

M P
the screen to indicate the magnitude of difference (e.g.,
0=no difference, 100=largest possible difference, controls.
etc.).63 Alternatively, they can select descriptors (e.g.,

O
a) I think there is a difference; b) I know there is a dif-
ference; c) there is a moderate difference; d) there is a Effect of skin color and pigmentation

C
very large difference).66 The VPS method was used
to compare images of facial skin with hyperpigment-
ed spots before and after 8 weeks of treatment.67 This
allows comparison of temporal effects and does not rely
on written documentation or the clinician’s memory to
evaluate ontogeny and treatment progression.
Naïve judge/patient assessment
In a similar fashion, images that represent a range of
severity for the condition of interest can be used to
determine the magnitude of differences that naïve
judges, patients or clients can detect and/or to relate
their perception to expert clinical opinion. In this
Photographic methods typically use the entire range
of wavelengths from white light (e.g., flash) for inter-
actions with the skin. Melanin, water, hemoglobin and
other chromophores absorb the incident light to vary-
ing extents, depending upon the wavelength (Figure 8).
The inherent skin coloration and the response to ultra-
violet radiation are used to assign a skin type from I-
VI, known as the Fitzpatrick Skin Type system (Table
V).69 The anthropologist Fredrick Von Luschan devel-
oped a color chart to classify and describe the col-
oration in the late 1900s (Figure 9).70 The influence of
chromophores on incident light varies considerably
across clinical populations. Skin coloration for a giv-

20 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA February 2010

IMAGING SKIN VISSCHER

TABLE V.—Skin Classification by Pigmentation (see Figure 9 for Luschan’s color).

Von Luschan’s Von Luschan’s
Type Effect of Light Exposure Description Description Color

I Always burns, never tans Pale, fair, freckles Very light 1-5
II Usually burns, sometimes tans Fair Light 6-10

A
III May burn, usually tans Light brown Intermediate 11-15
IV Rarely burns, always tans Olive brown Mediterranean 16-21
V Moderate constitutional pigmentation Brown Dark or brown 22-28

C
VI Marked constitutional pigmentation Black Very dark or black 29-36

DI
en individual varies with season due to differences in
the amount of light exposure.71
The variation in light absorption needs to be taken

E
into account with either image processing and/or wave-
length of image collection. One approach has been to

M ®
use reflectance spectroscopy. Reflectance spectrome-
ters use diodes to supply light of specific wavelengths,
i.e., 568 nm (green), 660 nm (red) and 880 nm

A
(infrared), to measure 1) erythema as hemoglobin from

T
absorbed and reflected light (red, green); and 2)

V
melanin from absorbed and reflected red or combina-

H
tions of red and infrared.72 Melanin (M) content is
approximated from red reflectance using this equa-

ER
tion: M=log10 (1/% red reflectance) and erythema (E)

IG
from: E=log10 (1/% green reflectance) - log10 (1/% red
reflectance).73 Shriver et al. used narrow band
reflectance spectroscopy and CIE L*a*b* tristimulus
Figure 9.—Von Luschan skin color chart.

IN YR
color (three specific wavelengths) to measure erythe-
ma, melanin, L* and a* in people of varying ethnici-
ty.73 The results (Table VI) show differences in skin
lightness and pigmentation across racial groups for
methods for separating erythema and pigmentation
have been a “necessary outgrowth” of research on
understanding the effects of environmental exposure
to ultraviolet radiation (UVB) on human skin and the

M P
healthy, nondamaged skin E and M are relatively inde-
pendent for low pigmentation and can be used to esti-
mate erythema and melanin content. However, for
influence of inherent skin pigmentation, dose, previ-
ous exposure, etc. In the L*a*b* color system, the

O
Individual Typology Angle (ITA) has been used to
dark skinned subjects, they are correlated and cannot determine pigmentation as follows:15
be infer redness or melanin content. This finding

C
demonstrates the difficulty in the evaluation of ery-
thema in dark-skinned patients and indicates that oth-
er methods must be used.
For skin conditions, e.g., irritant dermatitis, acne,
eczema, the extent of inflammation is of interest and
ITA=[arctan((L* - 50)/b*)] × 180/π

However, changes in color cause by changes in blood

apparent color is influenced by post inflammatory
responses (hypo and hyperpigmentation). Successful
evaluation of treatment efficacy depends upon ade-
quately separation of the responses due to increased
blood flow (e.g., irritant phase of irritant dermatitis)
from changes in barrier properties (i.e., skin dryness
due to hyperproliferation and altered desquamation) or
changes in pigmentation. The development of new
flow can influence this attribute.16 Wagner et al., made
refinements to the measurement of erythema and col-
or by adjusting the melanin (M) and erythema (E)
indices by the slope of the absorbance from 650 to 700
nm, to generate AM and EM, respectively.21 They con-
cluded that L*, M and AM were valid methods for
determining inherent color, but only the change in AM
could be used to assess skin responses (in this case to
UV treatment). The erythema response could be deter-
mined from changes in both a* and AE.

Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 21

VISSCHER IMAGING SKIN

Quantitation of specific areas of increased or Contrast agents

decreased skin pigmentation over a large area of is of
interest for solar lentigines, acne, etc. Miyamoto et
al. developed a controlled digital image capture and
analysis system to quantify the total area constituted
The extent of epidermal tissue injuries such as abra-
sions, fissures, and cracks can be difficult to assess
accurately, particularly in darker skinned patients.
Contrast agents, e.g., toluidine blue, fluorescein, cou-

A
by multiple hyperpigmented spots on the face (cheek pled with digital fluorescence image capture were
and periorbital regions).74 Following extraction of the used to quantify the extent of epidermal and oral

C
blue channel of the RGB image, the spots were select- mucosal injury as a function of skin pigmentation.78
ed, extracted and compared to the surrounding skin

I
Images were taken with blue light where fluorescein
using CIE L*a*b* values. The method is of sufficient emits an intense green light and analyzed for area and
sensitivity to determine the effectiveness of treatment intensity in groups with dark (inherent pigmentation,

E D
modalities relative to a vehicle control.75

Diffuse reflectance spectroscopy: recent developments

More recently, diffuse reflectance spectrometers
Type V & VI, with L from 35-48) and light (type I &
II, L from 63-72) skin. The extent of injury could be
quantified without interference from inherent pig-
mentation and may be applicable to other situations of

M ®
epidermal compromise.
(DRS) have added components (e.g., gratings) to
increase the number of discrete wavelengths and obtain
information at increments of 5-20 nm within the region

A
Imaging skin lesions

T
of 400-700 nm.27 In this mode, DRS can be used to sep-
arate the pigmentation (melanin), oxyhemoglobin, and Dermoscopy

V
deoxyhemoglobin. Reference spectra (white, dark)

H
are collected, the region of interest is measured, the

R
contribution due to surface reflection (specular
Dermoscopy is a simple imaging technique that
uses low magnification (10×), cross-polarization to

G
reflectance) is subtracted, and the apparent absorp- remove surface reflection and application of a liq-

E I
tion (A) is computed for each wavelength.76 The uid to increase light transmission into the epidermis
absorbance from melanin (Am) is derived from the and upper dermis.79 A meta-analysis of published
studies indicated that the use of a dermatoscope

IN YR
individual values in the region from 630-700 nm. After
increases the sensitivity for detection of melanoma
Am is subtracted from A, the absorbances for oxy and
relative to the naked eye alone.80 The capabilities of
deoxyhemoglobin are calculated from absorbtion val-
these hand held devices have been extended by the
ues at 580 nm (oxy-HB maximum) and 560 (deoxy-Hb
development and implementation of spectroscopic

M P
maximum). Values of the three chromophores are inde- methods. The goal is to obtain more detailed infor-
pendent when this method is used.76 mation, particularly about melanoma where diag-
The diffuse reflectance spectrometers described thus

O
nostic accuracy is difficult. Dwyer et al used DRS
far are designed to measure local areas of ~10-50 mm to collect spectral images from 400-700 nm at 20 nm
in diameter with a probe in contact with the skin sur- intervals and compared them with image analysis of

C
face. Additional information about the skin status with
respect to water, e.g., edema, can be obtained by adding
the near infrared region and collecting multiple absorp-
tion spectra from 400 to 1 000 nm, referred to as
“hyperspectral” imaging.77 As described for DRS to
separate the components of melanin and hemoglobin,
images are collected at 10-20 nm intervals. When large
areas are sampled with hyperspectral “cameras”, the
output data is a stack of images at each wavelength.
Image analysis methods extract the specific informa-
tion, e.g., color, hemoglobin, water. Erythema data
collected this way was highly correlated to the expert
clinical assessment (grades 0-4).77
3 mm excised tissue biopsies stained for melanin
(Masson Fontana). They determined melanin from
the difference in L* for 400 nm versus 420 nm images
and found an excellent correlation with convention-
al histology (r=0.68).81
The method of spectrophotometric intracutaneous
analysis (SIA) has moved from the research to the
clinical setting.82 SIA employs diffuse reflectance
spectroscopy over the range of 400-1 000 nm of ener-
gy and extracts features that can be related to the mor-
phology of the lesion for a sample area of 12-24 mm
in diameter. The output was validated with conven-
tional histology of tissue biopsies obtained after image

22 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA February 2010

IMAGING SKIN VISSCHER

Poor Moderate Excellent Almost perfect

Dermal melanin
Blood
displacement
Dermal melanin
globules

CA Blood
displacement
with blush

I
Asymmetry

Biaxial symmetry

D
Collagen holes
Erythematous

E
blush

Melanin globules

Blood globules

M ®
Figure 10.—Representative images from spectrophotometric intercuta-
neous analysis (SIA).
0 0.2 0.4 0.6
Bars indicate 95% confidence levels
0.8 0

A
Adapted from Moncrieff, British Journal of Dermatology, 2002, 246, 448-457

V T
collection. The results showed good specificity (80.1%)
and sensitivity (82.7%).82 The image processing pro-

H
cedures use the near infrared scans to map the quanti-
Figure 11.—Agreement between skin features from the SIA method and
conventional histology.

R
ty of collagen in the papillary dermis. Next, the total Other modalities: laser Doppler perfusion,

G
melanin, oxy-Hb and deoxy-Hb are extracted, sepa- ultrasound, and thermal imaging

E I
rated and quantified. Once they have been removed, the
amount of melanin that is physically located below While instruments like the Vancouver General Hos-
the dermal-epidermal junction can be isolated and

IN YR
analyzed. Representative images are shown in Figure
10.82 Features typically identified from standard his-
tology, including as dermal melanin, blood displace-
ment with blush, collagen holes, melanin globules,
pital Scar Scale and the Lund and Browder chart esti-
mation are used for burn area and severity, they are
not effective for determining the extent of healing or
treatment effectiveness.85 Scanning laser Doppler per-

M P
fusion imaging was effective for determining the rate
were compared for the SIA images and biopsies. Fig-
of re-epithelialization, need for skin grafting and treat-
ure 11 indicates the reliability and supports the use of
ment planning for scars.85 Scanning laser Doppler per-

O
the SIA method for most of the features. SIA has also
been applied to the quantitation of the effects of long fusion imaging was used to evaluate blood flow among
term ultraviolet exposure on facial skin, e.g., hyper- subjects wearing transparent burn masks. The results

C
pigmented spots and to evaluate the perception of age
and health status.83 The applicability of SIA for the
evaluation of common skin conditions has been demon-
strated by Kollias et al.84 Changes in erythema could
be used to quantify the irritant response to sodium lau-
ryl sulfate, inflammation due to histamine release,
changes in blood flow (by application of pressure),
inflammation induced by ultraviolet exposure and for
conditions of reactive hyperemia. Their findings sug-
gest applicability of this technique for the evaluation
of common skin conditions including irritant contact
dermatitis, allergic dermatitis, and pressure induced
injury.
showed significant differences in perfusion with and
without pressure and as a function to specific mask
treatment.86 The healing status of tissue injuries such
as wounds and burns is difficult to assess by live visu-
al and optically based imaging systems (e.g., photog-
raphy) perfusion cannot be easily determined in the
presence of other chromophores. Knowledge of per-
fusion status is essential for treatment planning and
determination of progress. Laser Doppler imaging was
used to evaluate the status of burns among 48 pedi-
atric patients with 85 burns over a period of 186 hours.
Perfusion data was related to re-epithelialisation and
predictive of grafting and scar management outcomes87.

Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 23

VISSCHER IMAGING SKIN

Three instruments, the TiVi imaging system (Wheels-
Bridge AB), the laser Doppler scanner (Moor Instru-
ments) and the laser speckle perfusion imager, were
compared in detail to assess their relative clinical util-
ity.88 They were evaluated in conditions of known
focal microscopy (RCM) and fluorescence excitation
spectroscopy, to determine the effect of skin pig-
mentation (African American versus Caucasian) on the
irritant response to surfactant.92 Both groups showed
SC disruption and epidermal spongiosis but damage

A
changes in blood flow, i.e., a topical analgesic (men- was more severe in lighter skin. Although a greater per-
thol), vasodilatation (methyl nicotinate), blanching centage of the fluorescence was absorbed in dark skin
(steroid), and post occlusive reactive hyperemia. The (due to increased melanin concentrations), the relative

IC
laser speckle and TiVi systems were able to detect
changes in the superficial papillary plexus that could
not be detected by the laser Doppler instrument. The
changes in epidermal proliferation versus baseline
were the not different. RCM holds promise as a bet-
ter and more accurate method for diagnosing malig-

D
laser Doppler was effective at measuring changes in the
dermis. The effects of occlusion could be measured

E
with both laser instruments but not readily with the
TiVi. O’Doherty urged consideration of the features of
each prior to use for a specific clinical condition and
nant melanoma and may allow more rapid interven-
tion.93 Multiphoton microscopy (MM) uses lasers
with pulses of femtoseconds and simultaneous absorp-
tion of two photons in the near infrared region to
achieve resolution at the sub-cellar level.94 Although

M ®
noted the need for further investigation.88
When combined information from laser Doppler per-
fusion imaging, thermal imaging, and nailfold capil-
work is in relatively early stages, investigators antic-
ipate its use for evaluating processes in transdermal
drug delivery and modifications at the level of the

A T
laroscopy, ultrasound imaging could differentiate patients
with systemic sclerosis from those with Raynaud’s dis-

V
ease and from healthy controls.89 Low echo (10 MHz)
stratum corneum.

H
ultrasound and thermal imaging detected inflammation

R
on the feet of diabetic patients that could not be found

G
with visual inspection, most likely due to interference
3D skin surface imaging

Many of the skin imaging methods are inherently

E I
from the thickened stratum corneum of the callus.90 two-dimensional in nature or rely on sequential 2D
scans to create a three dimensional image. Natural
curvatures of any body site can constrain the area of

IN YR
Confocal microscopy
In an effort to obtain highly detailed “histological”
information within the stratum corneum, epidermis
interest to relatively “flat” regions. The skin is high-
ly textured, as easily seen by inspection. Evaluation
of textural features such as wrinkles and fine lines is
frequently accomplished by inspection of high qual-

M P
and dermis, noninvasive in vivo microscopic tech-
niques have been developed and evaluated in research
ity 2D images taken with careful repositioning. Skin
surface texture can be measured from surface replicas

O
and clinical settings. The goal is to replace the invasive made with a silicone polymer. Stereomicroscopy, pro-
tissue biopsy with a technique that is not limited by the filometry and 3D camera systems with fringe projec-
artifacts of tissue preparation and sectioning prior to tion optics (e.g., PRIMOS) have been used to quantify

C
microscopy. The techniques for imaging skin include
optical coherence tomography (OCT), reflectance con-
focal microscopy, multiphoton microspectroscopy,
and confocal Raman spectroscopy. In OCT, light from
two paths achieves coherence and can penetrate up to
2 mm at with high resolution (10 µm).91 It has been
used to quantitatively characterize nonmelanoma skin
cancer because it can distinguish tumor borders from
normal skin. Epidermal thickening and edema have
been demonstrated for irritant dermatitis and psoriasis
and shows promise for characterizing sub-epidermal
features in blistering disease.91
Astner et al. used a combination of reflectance con-
texture (roughness) from replicas or skin in vivo (up
to ~ 25 cm2).95 The skin surface features of larger
areas and/or for irregularities in actual clinical situa-
tions, e.g., wounds, surgical scars, malformations,
burns, radiation dermatitis (breast tissue) or trauma can
be difficult to evaluate with these more localized meth-
ods. 3D skin surface data can be obtained from scan-
ning systems (e.g., mounted on a platform and con-
trolled by data acquisition software.96 Laser-based
scanners (e.g., Cyberware Rapid 3D Digitizer, Cyber-
ware, Inc., Monterrey, CA) operate on the principle of
triangulation. As a helium-neon laser light source
passes through two cylindrical lenses, the resulting

24 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA February 2010

IMAGING SKIN VISSCHER

vertical plane of light projects onto the surface of the
object. The highlighted profile is reflected from the
image mirrors to a video sensor and digitized in a
raster fashion to determine the 2D coordinates of 256
points along the profile surface. The scanner moves
related to, and usually correlated with clinical judg-
ment. Perhaps the clinician is relying more on imag-
ing methods than previously with the benefit of
increased efficiency. With “future vision”, the
approaches will be multimodal. One method is unlike-

A
along a linear trajectory performing 512 individual ly to tell the story. The era of “globalization” demands
surface contour scans in equal increments. Trigono- that skin imaging is done successfully and complete-
metric calculations of the 2D coordinates to 3D space ly across an extraordinarily diverse population of

IC
are performed. Resulting images are processed to
remove extraneous features, e.g., LS 3rd order poly-
nomial equation to remove the thigh curvature and
humans. The need for methods of clinical utility and
rapid data reduction is driven by an increased under-
standing of the complex processes in the skin and a

D
filtering utilities to remove noise from movement or
hair. Quantitative surface roughness parameters are

E
then calculated from the scan data with appropriate
software (e.g., TrueMap Software, TrueGage, N. Hunt-
ingdon, PA).97
desire to deliver cost-effective care that meets
patient/consumer expectations. Prevention and early
detection of tissue injury is dependent on objective,
quantitative skin imaging methods. The generation
of a coherent framework with quantitative endpoints

M ®
As an example 3D surface scanning was used to
determine differences in the severity of gynoid lipody-
strophy (cellulite). The effect of weight loss on sever-
may be facilitated by the reapplication of validated,
published strategies and approaches from one condi-
tion to another. Based on the current research, the

A T
ity was determined by comparing 3D surface rough-
ness, thigh fat levels and dermal tissue density (ultra-

V
sound) over six months. Significant differences were
future goal of better, less invasive diagnostic proce-
dures for skin disorders is likely to be reached. In

H
1966, renowned dermatologist, Dr. Albert M. Kligman
found for cellulite severity: Sa (average roughness, delivered a lecture entitled “Blind Man Dermatol-

R
average of the absolute distances of the surface profile ogy” in which he stressed the importance of quanti-

G
from the reference plane), Sq (square root of Sa, width tative skin measurements.100 He stated, “I hope to be

E I
or variance of the amplitude distribution function), St alive when the first blind medical graduate applies for
(vertical distance from the highest peak to the lowest residency training in dermatology; if he is as confident
valley), Spm (mean height of the highest peaks over the

IN YR
as I now am that sightlessness will be an inconve-
sample length), and Sz (mean of the vertical distance nience rather than an insuperable disability, the gold-
from the highest peaks to the lowest valleys over the en age will have begun.” It is possible to make the
sample length).98 The percent thigh fat and subregion
case that the golden age is here.
fat decreased and lean tissue increased. The dermal

M P
tissue density (ultrasound) decreased with weight loss,
but dermal thickness and the dermal-subcutaneous Riassunto

O
surface area were not different. Recently, Horton et
al., have demonstrated the use of computed tomogra- Metodiche di imaging cutaneo: passato, presente e pro-
phy with multidectector hardware for 3D volume ren-

C
dering of skin.99 They propose exciting uses of this
modality for skin surface characterization in condi-
tions such as cellulite.
Future perspective
In keeping with the title, imaging skin today con-
jures “images” of the past and present. Based on the
rich past history of skin evaluation, it seems clear that
the live visual clinical evaluation is still the gold stan-
dard. Presently, the data suggests that the output of
energy based (optical) imaging methods is always
spettive future
Le modalità di imaging cutaneo importanti nella valuta-
zione della varietà di patologie cutanee riscontrate in ambi-
to clinico vengono descritte con riferimento alle informa-
zioni fornite, ai vantaggi e alle loro limitazioni, allo stato
attuale e alle indicazioni per un ulteriore sviluppo. Le diver-
se metodologie utilizzano l’interazione di energia con la
cute, che penetra a diverse profondità nello strato corneo,
nell’epidermide, nel derma e nello stato sottocutaneo, un
sistema di rilevamento come la retina, pellicola oppure un
array digitale, e un sistema di processazione per frammen-
tare, analizzare e interpretare l’informazione. Allo stesso
modo, le aree di interesse, o obiettivi, hanno caratteristiche
comuni. Le patologie cutanee deviano dallo stato ideale o
normale per quanto riguarda l’integrità e la funzione della

Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 25

VISSCHER
cute. Una parte del compito nell’ambito delle metodiche
per immagine cutanee è di stabilire i criteri della condizio-
ne normale. Le deviazioni includono l’evidenza di rottura
della barriera, di infiammazione, di alterazione della pig-
mentazione e di modifiche vascolari. Chi utilizza l’ima-
ging cutaneo è spesso interessato dalla valutazione dell’e-
A
stensione e della gravità della malattia. Questa revisione
include il passato, il presente e il futuro della valutazione
visiva, della raccolta di immagini fotografiche, delle tecni-
C
che spettrofotometriche, dell’istologia non invasive, e del-
I
la scansione tridimensionale. Inoltre, gli autori presentano
le tecniche analitiche per la processazione e l’estrazione di
specifici parametri che forniscono informazioni circa il sot-
E
nale - Dermoscopia.D
tostante stato biologico.
Parole chiave: Malattie della pelle - Immagine tridimensio-
M ®
References
1. Imaging. The American Heritage Science Dictionary. Orlando, FL
A
USA: Houghton Mifflin Company; 2005.
T
2. Perednia DA. What dermatologists should know about digital imag-
ing. J Am Acad Dermatol 1991;25:89-108.
V
3. Rallan D, Harland CC. Skin imaging: is it clinically useful? Clin Exp
H
Dermatol 2004;29:453-9.
4. Galdino GM, Vogel JE , Vander Kolk CA. Standardizing digital pho-
R
tography: it’s not all in the eye of the beholder. Plast Reconstr Surg
G
2001;108:1334-44.
5. Caspers PJ, Lucassen GW, Carter EA, Bruining HA, Puppels GJ. In
E I
vivo confocal Raman microspectroscopy of the skin: noninvasive
determination of molecular concentration profiles. J Invest Dermatol
2001;116:434-42.
IN YR
6. Anderson RR , Parrish JA. The optics of human skin. J Invest Dermatol
1981;77:13-9.
7. Taylor S, Westerhof W, Im S, Lim J. Noninvasive techniques for the
evaluation of skin color. J Am Acad Dermatol 2006;54:S282-90.
8. Serup J. Skin irritation: objective characterization in a clinical per-
M P
spective. In: Wilhelm KP, Elsner P, Berardesca E, Maibach I, editors.
r6Bioengineering of the Skin: Skin Surface Imaging and Analysis.
Boca Raton: CRC Press; 1997. p. 261-73.
9. Stephen ID, Coetzee V, Law Smith M , Perrett DI. Skin blood perfu-
O
sion and oxygenation colour affect perceived human health. PLoS
One 2009;4:e5083.
10. Fink B, Matts PJ, Klingenberg H, Kuntze S, Weege B, Grammer K.
C
Visual attention to variation in female facial skin color distribution. J
Cosmet Dermatol 2008;7:155-61.
11. Fink B , Matts PJ. The effects of skin colour distribution and topog-
raphy cues on the perception of female facial age and health. J Eur Acad
Dermatol Venereol 2008;22:493-8.
12. Hunt RWG. The Reproduction of Color Chichester: Wiley; 2004.
13. Wyszecki G, Stiles, W.S. Color Science: Concepts and methods, quan-
titative data and formulae. New York: Wiley; 1982.
14. Susstrunk S, Buckley R, Swen S. Standard RBG color spaces.
IS&T/SID 7th Color Imaging Conference1999. p. 127-34.
15. Chardon A, Cretois I, Hourseau C. Skin colour typology and suntan-
ning pathways. Int J Cosmet Sci 1991;13:191-208.
16. Stamatas GN, Zmudzka BZ, Kollias N, Beer JZ. Non-invasive mea-
surements of skin pigmentation in situ. Pigment Cell Res 2004;17:618-
26.
17. Takiwaki H. Measurement of skin color: practical application and
theoretical considerations. J Med Invest 1998;44:121-6.
18 Nordlund JJ, Boissy RE. The biology of melanocytes. In: R. K.
26 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
IMAGING SKIN
Freinkel, Woodley, D.T. editor. The biology of the skin. New York:
Parthenon Publishing Group; 2001. p. 113-31.
19. Morgan JE, Gilchrest B , Goldwyn RM. Skin pigmentation. Current
concepts and relevance to plastic surgery. Plast Reconstr Surg
1975;56:617-28.
20. Knudsen A , Brodersen R. Skin colour and bilirubin in neonates. Arch
Dis Child 1989;64:605-9.
21. Wagner JK, Jovel C, Norton HL, Parra EJ , Shriver MD. Comparing
quantitative measures of erythema, pigmentation and skin response
using reflectometry. Pigment Cell Res 2002;15:379-84.
22. Jordan WE, Lawson KD, Berg RW, Franxman JJ, Marrer AM. Diaper
dermatitis: frequency and severity among a general infant popula-
tion. Pediatr Dermatol 1986;3:198-207.
23. Elsner P. Skin color. In: Berardesca E, Elsner P, Wilhelm KP, Maibach
HI, editors.0 Bioengineering of the skin: methods and instrumentation.
24.
25.
Boca Raton: CRC Press; 1995. p. 29-40.
Kawai K, Kawai J, Nakagawa M, Kawai K. Effects of detergents. In:
Wilhelm K, Elsner P, Berardesca E, Maibach HI, editors. Bioengi-
neering of the skin: skin surface imaging and analysis. Boca Raton:
CRC Press; 1997. p. 303-14.
Mattsson U, Jonsson A, Jontell M , Cassuto J. Digital image analysis
(DIA) of colour changes in human skin exposed to standardized ther-
mal injury and comparison with laser Doppler measurements. Com-
put Methods Programs Biomed 1996;50:31-42.
26. Nystrom J, Geladi P, Lindholm-Sethson B, Rattfelt J, Svensk AC ,
Franzen L. Objective measurements of radiotherapy-induced erythe-
ma. Skin Res Technol 2004;10:242-50.
27. Stamatas GN, Kollias N. Blood stasis contributions to the perception
of skin pigmentation. J Biomed Opt 2004;9:315-22.
28. Ben-Gashir MA , Hay RJ. Reliance on erythema scores may mask
severe atopic dermatitis in black children compared with their white
counterparts. Br J Dermatol 2002;147:920-5.
29. Black J, Baharestani M, Cuddigan J, Dorner B, Edsberg L, Langemo
D et al. National Pressure Ulcer Advisory Panel’s updated pressure
ulcer staging system. Urol Nurs 2007;27:144-50, 56.
30. Thomas DR, Rodeheaver GT, Bartolucci AA, Franz RA, Sussman
C, Ferrell BA et al. Pressure ulcer scale for healing: derivation and val-
idation of the PUSH tool. The PUSH Task Force. Adv Wound Care
1997;10:96-101.
31. George-Saintilus E, Tommasulo B, Cal CE, Hussain R, Mathew N,
Dlugacz Y et al. Pressure ulcer PUSH score and traditional nursing
assessment in nursing home residents: do they correlate? J Am Med
Dir Assoc 2009;10:141-4.
32. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ , Graeber M.
The eczema area and severity index (EASI): assessment of reliabili-
ty in atopic dermatitis. EASI Evaluator Group. Exp Dermatol
2001;10:11-8.
33. Fredriksson T , Pettersson U. Severe psoriasis—oral therapy with a new
retinoid. Dermatologica 1978;157:238-44.
34. Oranje AP, Stalder JF, Taieb A, Tasset C, de Longueville M. Scoring
of atopic dermatitis by SCORAD using a training atlas by investiga-
tors from different disciplines. ETAC Study Group. Early Treatment
of the Atopic Child. Pediatr Allergy Immunol 1997;8:28-34.
35. Pucci N, Novembre E, Cammarata MG, Bernardini R, Monaco MG,
Calogero C et al. Scoring atopic dermatitis in infants and young children:
distinctive features of the SCORAD index. Allergy 2005;60:113-6.
36. Sugarman JL, Fluhr JW, Fowler AJ, Bruckner T, Diepgen TL, Williams
ML. The objective severity assessment of atopic dermatitis score: an
objective measure using permeability barrier function and stratum
corneum hydration with computer-assisted estimates for extent of
disease. Arch Dermatol 2003;139:1417-22.
37. Angelova-Fischer I, Bauer A, Hipler UC, Petrov I, Kazandjieva J,
Bruckner T et al. The objective severity assessment of atopic der-
matitis (OSAAD) score: validity, reliability and sensitivity in adult
patients with atopic dermatitis. Br J Dermatol 2005;153:767-73.
38. Odio MR, O’Connor RJ, Sarbaugh F , Baldwin S. Continuous topi-
cal administration of a petrolatum formulation by a novel disposable
February 2010
IMAGING SKIN
diaper. 2. Effect on skin condition. Dermatology 2000;200:238-43.
39. Visscher MO. Update on the use of topical agents in neonates. New-
born & Infant Nursing Reviews 2009;9:31-47.
40. Horfelt C, Funk J, Frohm-Nilsson M, Wiegleb Edstrom D, Wennberg
AM. Topical methyl aminolaevulinate photodynamic therapy for
treatment of facial acne vulgaris: results of a randomized, controlled
study. Br J Dermatol 2006;155:608-13.
A
41. Leyden JJ, Shalita A, Thiboutot D, Washenik K, Webster G. Topical
retinoids in inflammatory acne: a retrospective, investigator-blind-
ed, vehicle-controlled, photographic assessment. Clin Ther
C
2005;27:216-24.
42. Pressure Ulcer Scale for Healing (PUSH). PUSH Tool 3.0: National
DI
Pressure Ulcer Advisory Panel; 1998. p. [Internet]. Available at
www.npuap.org [cited 2010, Feb 2].
43. Liguori V, Guillemin C, Pesce GF, Mirimanoff RO, Bernier J. Dou-
ble-blind, randomized clinical study comparing hyaluronic acid cream
to placebo in patients treated with radiotherapy. Radiother Oncol
E
1997;42:155-61.
44. Schmuth M, Wimmer MA, Hofer S, Sztankay A, Weinlich G, Linder
DM et al. Topical corticosteroid therapy for acute radiation dermati-
tis: a prospective, randomized, double-blind study. Br J Dermatol
M ®
2002;146:983-91.
45. Sullivan T, Smith J, Kermode J, McIver E , Courtemanche DJ. Rating
the burn scar. J Burn Care Rehabil 1990;11:256-60.
46. Barczak CA, Barnett RI, Childs EJ, Bosley LM. Fourth national pres-
A
sure ulcer prevalence survey. Adv Wound Care 1997;10:18-26.
T
47. Henderson CT, Ayello EA, Sussman C, Leiby DM, Bennett MA,
Dungog EF et al. Draft definition of stage I pressure ulcers: inclusion
V
of persons with darkly pigmented skin. NPUAP Task Force on Stage
H
I Definition and Darkly Pigmented Skin. Adv Wound Care 1997;10:16-
9.
R
48. De Luca D, Zecca E, Zuppa AA , Romagnoli C. The joint use of
G
human and electronic eye: visual assessment of jaundice and tran-
scutaneous bilirubinometry. Turk J Pediatr 2008;50:456-61.
E I
49. Bendeck SE , Jacobe HT. Ultrasound as an outcome measure to assess
disease activity in disorders of skin thickening: an example of the
use of radiologic techniques to assess skin disease. Dermatol Ther
IN YR
2007;20:86-92.
50. Rubegni P, Nami N, Poggiali S, Tataranno D, Fimiani M. Digital
image management project for dermatological health care environ-
ments: a new dedicated software and review of the literature. Skin
Res Technol 2009;15:148-56.
M P
51. Coelho SG, Miller SA, Zmudzka BZ , Beer JZ. Quantification of UV-
induced erythema and pigmentation using computer-assisted digital
image evaluation. Photochem Photobiol 2006;82:651-5.
52. Setaro M , Sparavigna A. Quantification of erythema using digital
O
camera and computer-based colour image analysis: a multicentre
study. Skin Res Technol 2002;8:84-8.
53. Aspres N, Egerton IB, Lim AC , Shumack SP. Imaging the skin. Aus-
C
tralas J Dermatol 2003;44:19-27.
54. Fogelberg A, Ioffreda M , Helm KF. The utility of digital clinical
photographs in dermatopathology. J Cutan Med Surg 2004;8:116-
21.
55. Oduncu H, Hoppe A, Clark M, Williams RJ , Harding KG. Analysis
of skin wound images using digital color image processing: a pre-
liminary communication. Int J Low Extrem Wounds 2004;3:151-6.
56. Weatherall IL , Coombs BD. Skin color measurements in terms of
CIELAB color space values. J Invest Dermatol 1992;99:468-73.
57. Colorimetry. 2nd edition. CIE publications No. 15.2. Colorimetric
Illuminants (CIE S001); Colorimetric Observers (CIE S002). Vienna:
Central Bureau of the CIE; 1986.
58. Visscher M, Canning J, Said D, Wickett R, Bondurant P. Effect of
hand hygiene regimens on skin condition in health care workers. Am
J Infect Control 2006;34:S98-110.
59. Hinkel B. The focal easy guide to photoshop CS2. Burlington: Focal
Press; 2006.
60. Bahaskaran V, Konstantinides K. Image and Video Compression Stan-
Vol. 145 - No. 1 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
VISSCHER
dards: Algorithms and Architectures. Norwell: Kluwer Academic
Publishers; 1997.
61. Mark R, Billo, E. Application of digital image enhancement in rock
art recording. Fifth International Rock Art Symposium. Tarija2000.
62. Westerhof W, van Hasselt BA , Kammeijer A. Quantification of UV-
induced erythema with a portable computer controlled chromame-
ter. Photodermatol 1986;3:310-4.
63. Canning J, Barford B, Sullivan D, Wickett R , Visscher M. Use of
digital photography and image analysis techniques to quantify erythema
in health care workers. Skin Res Technol 2009;15:24-34.
64. Visscher M, Davis J, Wickett R. Effect of topical treatments on irri-
tant hand dermatitis in health care workers. Am J Infect Control
65.
66.
2009;37:842 e1- e11.
Kosmopoulos DI, Tzevelekou FL. Automated pressure ulcer lesion
diagnosis for telemedicine systems. IEEE Eng Med Biol Mag
2007;26:18-22.
Visscher M, Chatterjee R EJ, LaRuffa AA, Hoath SB. Biomedical
assessment and instrumental evaluation of healthy infant skin. Pedi-
atr Dermatol 2002;19.
67. Hakozaki T, Minwalla L, Zhuang J, Chhoa M, Matsubara A, Miyamo-
to K et al. The effect of niacinamide on reducing cutaneous pigmen-
tation and suppression of melanosome transfer. Br J Dermatol
2002;147:20-31.
68. Denecker K, De Neve P, Van Assche S, Van de Walle R, Lemahieu I,
Philips W. Psychovisual Evaluation of Lossy CMYK Image Com-
pression for Printing Applications. Computer Graphics Forum
2002;21:5-17.
69. Weller R, Hunter J, Savin J, Dahl M. Cinical dermatology. 4th edition.
Malden, Massachusetts, USA: Blackwell Publishing; 2008.
70. von Luschan F. Beitrage zur Volkerkunde der Deutschen Schutzge-
bieten. Berlin: Deutsche Buchgemeinschaft; 1897.
71. Lock-Andersen J , Wulf HC. Seasonal variation of skin pigmenta-
tion. Acta Derm Venereol 1997;77:219-21.
72. Clarys P, Alewaeters K, Lambrecht R, Barel AO. Skin color mea-
surements: comparison between three instruments: the Chromame-
ter(R), the DermaSpectrometer(R) and the Mexameter(R). Skin Res
Technol 2000;6:230-8.
73. Shriver MD, Parra EJ. Comparison of narrow-band reflectance spec-
troscopy and tristimulus colorimetry for measurements of skin and hair
color in persons of different biological ancestry. Am J Phys Anthro-
pol 2000;112:17-27.
74. Miyamoto K, Takiwaki H, Hillebrand GG , Arase S. Development
of a digital imaging system for objective measurement of hyperpig-
mented spots on the face. Skin Res Technol 2002;8:227-35.
75. Bissett DL, Robinson LR, Raleigh PS, Miyamoto K, Hakozaki T, Li
J et al. Reduction in the appearance of facial hyperpigmentation by top-
ical N-undecyl-10-enoyl-L-phenylalanine and its combination with
niacinamide. J Cosmet Dermatol 2009;8:260-6.
76. Stamatas GN, Zmudzka BZ, Kollias N, Beer JZ. In vivo measure-
ment of skin erythema and pigmentation: new means of implementation
of diffuse reflectance spectroscopy with a commercial instrument.
Br J Dermatol 2008;159:683-90.
77. Stamatas GN , Kollias N. In vivo documentation of cutaneous inflam-
mation using spectral imaging. J Biomed Opt 2007;12:051603.
78. Visscher MO, Sullivan D, Sullivan S, Barford B, Dock M , Sommers
MS. Quantitation of epidermal and mucosal tissue injury using con-
trast agents and imaging techniques. Skin Res Technol 2009;15:180-
6.
79. Malvehy J, Puig S, Argenziano G, Marghoob AA, Soyer HP. Der-
moscopy report: proposal for standardization. Results of a consensus
meeting of the International Dermoscopy Society. J Am Acad Dermatol
2007;57:84-95.
80. Vestergaard ME, Macaskill P, Holt PE , Menzies SW. Dermoscopy
compared with naked eye examination for the diagnosis of primary
melanoma: a meta-analysis of studies performed in a clinical setting.
Br J Dermatol 2008;159:669-76.
81. Dwyer T, Muller HK, Blizzard L, Ashbolt R, Phillips G. The use of
27
 VISSCHER IMAGING SKIN

spectrophotometry to estimate melanin density in Caucasians. Can-
cer Epidemiol Biomarkers Prev 1998;7:203-6.
82. Moncrieff M, Cotton S, Claridge E, Hall P. Spectrophotometric intra-
cutaneous analysis: a new technique for imaging pigmented skin
lesions. Br J Dermatol 2002;146:448-57.
83. Matts PJ. New insights into skin appearance and measurement. J
Investig Dermatol Symp Proc 2008;13:6-9.
91. Mogensen M, Thrane L, Joergensen TM, Andersen PE, Jemec GB.
Optical coherence tomography for imaging of skin and skin dis-
eases. Semin Cutan Med Surg 2009;28:196-202.
92. Astner S, Burnett N, Rius-Diaz F, Doukas AG, Gonzalez S , Gonzalez
E. Irritant contact dermatitis induced by a common household irri-
tant: a noninvasive evaluation of ethnic variability in skin response.
J Am Acad Dermatol 2006;54:458-65.

A
84. Kollias N, Seo I, Bargo PR. Interpreting diffuse reflectance for in 93. Hofmann-Wellenhof R, Wurm EM, Ahlgrimm-Siess V, Richtig E,
vivo skin reactions in terms of chromophores. J Biophotonics Koller S, Smolle J et al. Reflectance confocal microscopy—state-of-
2010;3:15-24. art and research overview. Semin Cutan Med Surg 2009;28:172-9.

C
85. Cho JK, Moon DJ, Kim SG, Lee HG, Chung SP, Yoon CJ. Relation- 94. Tsai TH, Jee SH, Dong CY, Lin SJ. Multiphoton microscopy in der-
ship between healing time and mean perfusion units of laser Doppler matological imaging. J Dermatol Sci 2009;56:1-8.

86.

I
imaging (LDI) in pediatric burns. Burns 2009;35:818-23.
Allely RR, Van-Buendia LB, Jeng JC, White P, Wu J, Niszczak J et al.
Laser Doppler imaging of cutaneous blood flow through transparent

D
face masks: a necessary preamble to computer-controlled rapid pro-
totyping fabrication with submillimeter precision. J Burn Care Res
95. Jacobi U, Chen M, Frankowski G, Sinkgraven R, Hund M, Rzany B
et al. In vivo determination of skin surface topography using an opti-
cal 3D device. Skin Res Technol 2004;10:207-14.
96. Smalls LK, Lee CY, Whitestone J, Kitzmiller WJ, Wickett RR , Viss-
cher MO. Quantitative model of cellulite: three-dimensional skin

E
2008;29:42-8. surface topography, biophysical characterization, and relationship to
87. Mill J, Cuttle L, Harkin DG, Kravchuk O, Kimble RM. Laser Doppler human perception. J Cosmet Sci 2005;56:105-20.
imaging in a paediatric burns population. Burns 2009;35:824-31. 97. Precision Devices, Inc. Surface Metrology Guide2003. [Internet].
88. O’Doherty J, McNamara P, Clancy NT, Enfield JG, Leahy MJ. Com- Available from http://www.predev.com [cited 2010, Feb 2].

M ®
parison of instruments for investigation of microcirculatory blood
flow and red blood cell concentration. J Biomed Opt 2009;14:034025.
89. Murray AK, Moore TL, Manning JB, Taylor C, Griffiths CE, Herrick
AL. Noninvasive imaging techniques in the assessment of scleroder-
98. Smalls LK, Hicks M, Passeretti D, Gersin K, Kitzmiller WJ, Bakhsh
A et al. Effect of weight loss on cellulite: gynoid lypodystrophy.
Plast Reconstr Surg 2006;118:510-6.
99. Horton KM, Johnson PT, Heath DG, Ney DR, Fishman EK. Three-

A
ma spectrum disorders. Arthritis Rheum 2009;61:1103-11. dimensional volume rendering and display of skin and subcutaneous

T
90. Nishide K, Nagase T, Oba M, Oe M, Ohashi Y, Iizaka S et al. Ultra- tissues. Applied Radiology 2009;6-13.
sonographic and thermographic screening for latent inflammation in 100. Kligman AM. Blind man dermatology. Journal of the Society of

V
diabetic foot callus. Diabetes Res Clin Pract 2009;85:304-9. Cosmetic Chemists 1966:506-9.

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