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DOI: 10.1111/j.1468-3083.2010.03837.

x JEADV

REVIEW ARTICLE

Principles of high-frequency ultrasonography for


investigation of skin pathology
D Jasaitiene,†,* S Valiukeviciene,† G Linkeviciute,† R Raisutis,‡ E Jasiuniene,‡ R Kazys‡

Department of Skin and Venereal Diseases of Kaunas University of Medicine, Kaunas, and ‡Ultrasound Institute, Kaunas
University of Technology, Kaunas, Lithuania
*Correspondence: D Jasaitiene. E-mail: odos.veneriniu.ligu.klinika@kmuk.lt

Abstract
Ultrasonography is a valuable diagnostic tool widely used in medicine. During the last three decades, this non-
invasive skin imaging method has been extended to dermatology. High-frequency ultrasonography with higher than
20 MHz scanners is well-established for measuring tumour thickness and skin thickness when treating inflammatory
skin diseases such as scleroderma or psoriasis. High-frequency ultrasonography has become extremely helpful for
the preoperative assessment of skin melanoma. The correlation between ultrasonic and histological measurements
of melanomas thickness is significantly similarly good using transducers of 20, 75 or 100 MHz frequency (r range
from 0.895 to 0.99) and better compared with transducers of 7.5 MHz frequency (r = 0.76). The preoperative
sonographically estimated thickness of skin melanoma is sometimes overestimated, because of an underlying
inflammatory infiltrate and other reasons. Assessment of skin melanoma thickness using transducers of 100 MHz
frequency has better agreement with histology, compared with ultrasonography with 20 MHz transducers. However,
the ultrasonic penetration depth is limited to 1.5 mm in case of 100 MHz. The newer ultrasonic techniques such as
high-frequency ultrasonography and colour Doppler sonography could be used for assessment of the tumour
vascularization and its metastatic potential. The wide variety of diagnostic information provided by high-frequency
ultrasonography undoubtedly improves the management of oncological and inflammatory skin conditions and
underlines its essential position in dermatological practice.
Received: 1 April 2010; Accepted: 5 August 2010

Keywords
dermatology, imaging, skin, tumours, ultrasonography, ultrasound

Conflicts of interest
None declared.

Introduction Subsequently, transducers with ultrasound frequencies of 100 and


Since the introduction of ultrasonography into medical diagnostics 150 MHz were developed that could depict the fine structure of the
about 50 years ago, this technique has grown to become the most epidermis, and their clinical value is currently under evaluation.2–7
frequent imaging method in medicine. This is attributed to its ver-
satility, unlimited repeatability with high diagnostic value and the Fundamental physics and ultrasound phenomena
lack of risk to the patient. This article reviews the applications of Ultrasound is elastic waves with frequency above 20 kHz, which
ultrasonography in dermatology focusing on preoperative mea- represents the upper frequency limit of human hearing. Ultrasonic
surement of tumour thickness. waves are generated by an ultrasonic transducer that can transform
Ultrasonography for measuring skin thickness was for the first an electrical current of the driving generator into a mechanical
time performed by Alexander and Miller using an A-mode device vibration. Thus, a very short ultrasound impulse is created. Vibra-
in 1979.1 Great progresses in the development of high-frequency tions from the ultrasonic transducer are transmitted into the med-
scanners occurred since that time. Studies on B-mode ultrasonog- ium under investigation and propagate in the form of an
raphy of the skin using 20 megahertz (MHz) prototypes followed ultrasonic wave. The propagation speed of ultrasonic wave is
in the next decades in Europe and Japan. These appliances have denoted by ultrasound velocity in the medium. The ultrasonic
A-, B- and C-scans, optional 3D reconstruction, and further wave is partially reflected at an interface separating two media of
transducers with 30 and 50 MHz frequency at their disposal. different acoustic impedance. The reflected wave is detected by the

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JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
376 Jasaitiene et al.

same transducer the mechanical vibration being transformed into Table 1 The dependence of axial (depth) resolution and pene-
electrical excitation.5,6 tration depth on the frequency of ultrasonic waves
Ultrasonic transducers – which are thin disc-shaped crystals Frequency, Maximum Axial resolution
made out of piezoelectric materials – generate acoustic energy MHz penetration, (1580 m ⁄ s ⁄
mm frequency), lm
when a voltage is applied to them. Acoustic vibrations are gener-
10 35 158
ated when those piezoelectric materials expand and contract. First
20 10 79
transducers were made from quartz; newer materials include lith-
30 6 53
ium sulphate, ceramics and plastic polymers. These newer materi-
50 4 32
als have allowed the development of transducers that produce
75 3 21
higher frequencies, which are of special interest for dermatologists
100 1.5 16
because the wavelengths of higher frequencies are smaller and
therefore better resolution of small objects located near the skin
surface is achieved.6 At present, the transducers for examination of to distinguish. The lateral resolution is measured perpendicular to
regional lymph nodes and soft tissue tumours operate in the 7.5– the direction of wave propagation, i.e. parallel to the skin. Axial
15 MHz range, while the frequency of transducers used to evaluate resolution is limited physically by the wavelength. The ultrasound
skin structure is in the range from 20 to 100 MHz. velocity (c), frequency (f) and the wavelength (k) are related:
Usually, ultrasound velocity in the human skin is reduced when k ¼ c=f . Shorter wavelength is required to achieve better axial res-
the water content of the tissue is greater, and is increased when olution. Axial resolution also depends on the bandwidth of the
the collagen concentration is higher. Several ultrasonic velocity transducer. Lateral resolution depends on the diameter and central
values have been reported for human skin, ranging from 1498 up frequency of the transducer, the width of the beam at the focus
to 1710 m ⁄ s.5 According to the information provided by Wei- zone and the spatial scanning step of the ultrasonic transducer.5
chenthal et al., in the tissue of human skin affected by melanoma The relationship of axial resolution and penetration depth with
the ultrasound velocity deviates only by 1% from the value the frequency of ultrasonic waves used for the investigation of
obtained in the case of healthy skin.5,8 human skin is presented in Table 1.5,11
If the ultrasound velocity in the skin is known, it is possible to
calculate skin and ⁄ or tumour thickness in vivo, from the expres- Imaging techniques
sion l ¼ c  t=2, where t is the time separating echoes generated by Usually, the result of ultrasonic imaging is presented in the form
the external medium–epidermis interface and the dermis–subcutis of A-scan (measurement at one point, showing the thickness of
interface, and c is ultrasonic velocity. The maximum thickness of different layers of the skin), B-scan [two-dimensional (2D), cross-
epidermis is up to 0.3 mm and of dermis – up to 2.5 mm.9 In the sectional view of the skin] and C-scan (2D view at some depth
case when pulse-echo set-up is used, ultrasonic waves propagate parallel to the surface of the skin) images.4–6 The principles of
through the skin and are reflected back. Normal and diseased skin ultrasonic imaging of the skin structure are presented in Fig. 1.
thickness has been measured in vivo by ultrasound.5,10 A-scan image of the skin reveals the amplitude of the echo
The attenuation of an ultrasonic wave during propagation is the reflected by the interfaces between layers of the skin (dermis–sub-
reduction in vibration amplitude and the intensity of the wave cutis, normal tissue-tumour). The different echoes recorded on-
during propagation. This reduction results from the absorption of line are of different amplitudes and are recorded according to a
the ultrasonic energy by the tissue and its transformation into time scale. The time of acoustic wave propagation is related to the
heat, from the natural divergence of the ultrasonic waves related distance. A-scan imaging is used to measure skin thickness in vivo.
to the geometry of the transducer, and to the diffusion (scattering) From the velocity of ultrasonic waves in the skin (the mean value
of the wave because of the heterogeneity of the tissue being propa- equal to 1600 m ⁄ s) and the time taken for the propagation of the
gated. It increases when the frequency used is higher. This prop- ultrasonic signal, it is possible to calculate the thickness of the
erty is used to characterize tissue according to its physical skin.5,12
properties, in particular by measuring ultrasound attenuation. In B-scan image is a 2D scan procedure using the same principle
addition, the attenuation limits the depth of penetration because as A-scan, but combined with longitudinal scanning, the combina-
the higher the central frequency, the smaller the depth of penetra- tion of which provides acquisition of several A-scans side by side.
tion is.5,11 The amplitudes of such group of A-scans are represented by
In the case of skin investigation, it is necessary to distinguish appropriate colour (shade) in 2D echographic image of the section
the different layers – epidermis, dermis and subcutis. The axial res- of the skin. In this type of image, the different shades of grey
olution is measured in the direction of the propagation of the depend on the echo (strength) detected from the corresponding
ultrasonic wave, which is excited perpendicular to the surface of anatomic structure. Such type of imaging is important in nowa-
the skin by the ultrasonic transducer. It is the shortest distance days dermatological research and clinical dermatology. It provides
separating the layers of the skin that the ultrasonic device is able an echographic image of the internal structure of the skin and

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JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
Principles of high-frequency ultrasonography 377

(a) Measurement point distinguishes the epidermis, papillary and reticular dermis, and
pilosebaceous units and subcutis.5,12
C-scan image is conventionally displayed as a 2D image but is
reconstructed from a three-dimensional data set which is obtained
from several B-scan images. Computerized reconstruction of data
obtained at such parallel cross-sections provides reconstruction of
the skin structure, as long as they are precisely identified in space.
This is particularly valuable for the reconstruction of tumours.5

Technical equipment
(b) Ordinary ultrasonic equipment for skin investigation consists of
an ultrasonic transducer of sufficiently high frequency (about
Imaging plane 15 MHz), an ultrasonic unit of excitation, reception and digitiza-
tion, and a computer for the control of data acquisition and visu-
alization. The transducer should be moved along the scanning axis
to obtain 2D ultrasonic image (B-scan imaging). Movement is
achieved with a small DC motor. The motor is linked with an
ultrasonic unit of excitation, reception and digitization. Particular
position of the ultrasonic transducer in the scanning path is esti-
mated using a position encoder. In the case of C-scan imaging, the
ultrasonic transducer should be moved along two independent
axes that are perpendicular to each other, and therefore two DC
(c) motors and position encoders should be used. As a result of the
large impedance mismatch between the air and the skin, the cou-
pling liquid (gel) between the transducer and the surface of the
skin should be used.5
For higher frequency ultrasonic examinations, there are differ-
ent ultrasound systems available in the market, for example: the
Imaging plane Episcan I-200 (Longport, Inc, Silchester, UK), the DermaScan C
(Cortex Technology, Hadsund, Denmark) and the DUB-USB
Figure 1 The principles of ultrasonic imaging of the skin struc- (Taberna pro medicum, Luneburg, Germany). The characteristics
ture: (a) A-scan, (b) B-scan and (c) C-scan. of the commercially available ultrasonic equipment for skin inves-
tigation are presented in Table 2.

Table 2 Characteristics of the commercially available 20–50 MHz frequencies ultrasonic equipment for skin investigation (2D imag-
ing, B-scan)

Equipment, manufacturer Episcan I-200, DermaScan C, Cortex DUB-USB, Taberna


Longport, Inc. Technology pro medicum
Analogue-to-digital converter 200 MHz, 8 bits (256 levels – 100 MHz, 8 bits (256 levels of
of amplitude) amplitude)
Scan (penetration) depths, mm 3.8–22.4 10–20 (depends on focal 8–10
distance of the transducer)
Axial resolution, lm Up to 40 60 72
Lateral resolution, lm – 130 –
Central frequency of the 20, 50 20 22
transducer, MHz
Scan lateral length, mm 15 – 12.8
Scan rate, frame per second 1 8 2.5
Type of visualization A-scan, B-scan (envelopes) A-scan, B-scan (envelopes) A-scan, B-scan (envelopes)
Combination with PC Combined with embedded Combined with embedded Separate portable device,
PC in minitower design PC in minitower design connection with PC via
USB 2.0
–, no information available.

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JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
378 Jasaitiene et al.

All transducers of such equipment are scanned mechanically, the thickness of melanomas and basal cell carcinomas showed
and the coupling water-like liquid is applied in all cases. 2D scan- lower correlation between ultrasonometric and histometric
ners for B-scan imaging are available in portable configurations thickness.28–32 Overestimation of skin tumour thickness resulting
for use with handheld ultrasonic transducers. Scanners for C-scan from the impossibility of differentiating lymphocytic infiltrates
imaging, combined with flexible arm holding the scanning head, or underlying nevus cells from melanoma tissue has been
usually are installed into a specialized transportation cart and are reported.33,34 The location of skin tumours in some areas (the
not portable. The price of such system is sufficiently high. More- head, nail and genitalia) can influence the ultrasonographic over-
over, only one portable 2D scanning system DUB-USB is assem- estimation as well.31 Routine histology using conventional for-
bled as a separate device that can be connected with any PC via malin-paraffin processing frequently distorts the anatomy of the
USB 2.0 interface. Other portable 2D systems are combined with horny layer and may result in artefacts including shrinkage of
PC in the same non-demountable assembly. To our knowledge, the tissue.35 A further important factor that may explain differ-
the commercially available ultrasonic equipment evaluated during ences between in vivo and ex vivo measurements is the natural
literature review has some limitations from the viewpoint of the shrinkage of the skin occurring after excision, particularly evident
investigation of skin thickness and structures.13–17 Usually, only for the dermis.35 Some melanomas are too thin (0.1 mm) to
envelope of the signal is being visualized. A large amount of infor- be visualized with 20 MHz ultrasound.36,37 The lowest ultraso-
mation is lost from the raw radiofrequency (RF) signal, and the nometric accuracy was observed in melanomas with a tumour
RF signal is not accessible to the user for further processing and thickness smaller than 1 mm.24,26,29,33 It has been indicated
analysis. A small number of scale values is being visualized – typi- that thickness assessed by ultrasonography in thin tumours
cally, 256 levels of amplitude (48 dB), only 8 bits. Moreover, usu- can be overestimated (in 15%), and in thick ones – underesti-
ally the sampling frequency does not exceed 100 MHz. The review mated (in 7%).29 Transducer of 100 MHz frequency possesses
of ultrasonic systems that are used in dermatological practice and the capability of high resolution imaging up to 1.5 mm depth
suggestions how to improve them are published recently.18 It of penetration with a much better resolution than the well-
should be noticed that a capacitive micromachined ultrasonic established 20 MHz technique, and tumour thickness measure-
transducers are used more and more in the field of high-frequency ments of thin melanomas using transducer of 100 MHz results
arrays (up to 50 MHz), and therefore they are becoming very per- in better agreement with histology, compared with transducer
spective in medical imaging. Such arrays have wide bandwidth of 20 MHz frequency.35 However, the penetration depth is
and would allow the use of dynamic focusing and higher frame limited to 1.5 mm in case of 100 MHz.
rates.19 Ultrasonography is a non-invasive technique and thus should
be ideally suited for preoperative assessment of invasion depth of
Investigation of skin tumours skin tumours, and has a high degree of accuracy, as shown by
Ultrasonography using ultrasonic transducers of 15 MHz fre- linear regression analysis (Pearson’s correlation coefficient r)
quency or more can clearly define the skin layer morphology (Table 3). Bland and Altman have pointed out that when a com-
including changes in the epidermal thickness.20 Thus, adjustments parison of two clinical measurements of the same criterion is
of focus, transmission frequency, or both give – in a single exam- made, the use of the correlation may be misleading.38 The correla-
ination – a complete view of the skin and deeper structures tion coefficient measures the strength of the relationship between
(muscles, tendons or bone margins), with minimal dispersion of the variables but does not necessarily measure the agreement
the sound energy waves.21–23 between them. Bland and Altman agreement includes the numeri-
In skin cancer – especially melanoma – preoperative ultrasono- cal identity between the test results of two different methods, uses
graphic measurement of tumour thickness could be an important the differences between the paired measurements, and is suggested
parameter for planning surgery and predicting the prognosis for to be a more useful indication as to whether one method can be a
the patient. Even if some inaccuracy in measurement of thin valid substitution for another.38 This statistical analysis shows that
(pT < 0.4 mm) or very thick tumours (pT > 7.6 mm) in compar- ultrasonography usually generates higher value for tumour thick-
ison with histology has been shown, distinguishing between thick ness compared with conventional thickness measurement.35 More-
(>1 mm) and thin melanomas is important for determining safety over, Tacke et al. revealed greater differences between sonometry
margins for the excision of the primary tumour and for the indi- and histometry calculating absolute and relative differences
cation for sentinel lymph node biopsy in a potential one-time between them.39
surgical procedure.24–27 Some studies demonstrated that the number and size of vessels
A fair correlation (r ‡ 0.9) between ultrasonic and histological visualized with colour Doppler sonography (CDS) significantly
measurements of melanoma thickness was obtained by many correlate with evaluation of vessels by immunochemical methods
authors (Table 3). Most of these ultrasonographic studies used and the rate of metastasis of melanoma.29,34,40 Therefore, intra-
20 MHz probes. Results of several studies that have used ultra- tumour angiogenesis evaluated with CDS could be used to identify
sonic transducers of 7–15 MHz frequencies for assessment of melanomas with a high metastatic potential. However, this helpful

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JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
Principles of high-frequency ultrasonography 379

Table 3 Correlation between the histological and ultrasound estimation of skin tumour thickness

Investigators, year Frequency of Studied skin tumours Correlation*


ultrasound (MHz)
50
Reali et al., 1989 20 Melanomas (N = 58) Yes (r = 0.895)
51
Gassenmaier et al., 1990 20 Melanomas (N = 72) Yes (r = 0.97)
52
Hoffman et al., 1992 20 Melanomas (N = 54) Yes (r = 0.94)
36
Fornage et al., 1993 20 Malignant (N = 45, including four melanomas) Yes (r = 0.95) for melanomas
and benign (N = 155) skin lesions
39
Tacke et al., 1995 20 Melanomas (N = 259) Yes (r = 0.88)
53
Partsch et al., 1996 20 Melanomas (N = 58) Yes (r = 0.92)
33
Krahn et al., 1998 20 Melanomas (N = 39), Yes (r = 0.95 and r = 0.93)
melanocytic nevi (N = 41)
54
Solivetti et al., 1998 20 Pigmented skin lesions (N = 120) Yes (r = 0.93)
55
Hoffman et al., 1999 20 Melanomas (N = 264), benign Yes (r = 0.97)
pigmented lesions (N = 417)
28
Ulrich et al., 1999 7.5 and 20 Melanomas (N = 249) Yes (r = 0.76 and r = 0.94)
34
Lassau et al., 1999 20 Melanomas (N = 27) Yes (r > 0.95)
56
Lassau et al., 2002 20 Melanomas (N = 69) Yes (r > 0.96)
24
Serrone et al., 2002 20 Melanomas (N = 193) Yes (r = 0.95)
26
Pellacani et al., 2003 20 Melanomas (N = 40) Yes (r = 0.89)
37
Bessound et al., 2003 20 Pigmented skin lesions (N = 130) Yes (r > 0.96)
29
Lassau et al., 2006 12 or 13 Melanomas (N = 111) Yes (r > 0.93)
35
Gambichler et al., 2007 20 and 100 Melanomas (N = 13), Yes (r = 0.99) for both
melanocytic nevi (N = 37) frequencies
57
Guitera et al., 2008 75 Melanomas (N = 52), Yes (r = 0.91)
melanocytic nevi (N = 36)
30
Bobadilla et al., 2008 7–15 Basal cell carcinomas (N = 23) Yes (r = 0.90)
27
Machet et al., 2009 20 Melanomas (N = 31) Yes (moderate agreement
according to Bland and Altman)
31
Hayashi et al., 2009 15 or 30 Melanomas (N = 68) Yes (r = 0.89)
32
Vilana et al., 2009 10 Melanomas (N = 54) Yes (r = 0.93)
*Between the histological and ultrasound estimation of skin tumour thickness; N, number of studied tumours; r, Pearson’s correlation coefficient.

tool is usually available only at conventional ultrasound devices can have good correlation in terms of the length and the width of
(up to 18 MHz). a tumour (r = 0.71 and r = 0.79, respectively).41 High-frequency
The diagnostics of pigmented skin lesions is a major clinical ultrasonographic measurements of the depth and regression of
part of the activity of a dermatologist who must always determine basal cell carcinomas after photodynamic therapy potentially offer
the risk of malignant melanoma and adapt the treatment strategy. a non-invasive guide to further treatment planning and follow-up
When analysing the ultrasonographic shapes or echo signs, non- of such patients.42 Basal cell carcinomas can also show a mixed
significant differences were found between benign and malignant echogenicity. When the tumours extend beyond the dermis–sub-
skin tumours, and ultrasonography alone is not capable to identify cutis border, the demarcation may become difficult because apart
the final diagnosis. However, it can rather well define distinct cate- from connective tissue septae, the subcutaneous fatty tissue is also
gories of skin lesions – benign non-vascular or vascular tumours; hypoechogenic. In addition, the deep tumour borders of basal cell
malignant tumours; inflammatory and infectious lesions; exoge- carcinomas cannot be visualized by 20 MHz. In these cases, ultra-
nous skin components; and nail lesions.23 A large retrospective sonography with transducers of 13–15 MHz frequency may be
study of 4338 ultrasonographic skin examinations showed that the helpful.6
addition of ultrasonography increased the correctness of clinical
diagnosis from 73% to 97%.23 Overall sensitivity of ultrasonogra- Other skin conditions
phy when diagnosing distinct categories of skin lesions can reach Other applications of high-frequency ultrasonography are skin
99%, and specificity – 100%.23 thickness measurement in inflammatory or fibrosing diseases such
Ultrasonographic morphology of melanomas and nevi show a as localized scleroderma, progressive systemic sclerosis, chronic
hypoechogenic, homogeneous and well-defined pattern, whereas sclerodermiform graft-versus-host disease, psoriasis or lichen
basal cell carcinomas are more heterogeneous with poorly defined planus. Ultrasonography with 20 MHz transducers helps to objec-
margins (Figs 2,3). Clinical and ultrasonographic measurements tify treatment response. Application of ultrasonography can also

ª 2010 The Authors


JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
380 Jasaitiene et al.

(a) (a)

(b) (b)

(c) Figure 3 Nodular melanoma. (a) Clinical image. (b) Ultrasonic


image of 14 MHz shows hypoechogenic, homogeneous and
well-defined structure, tumour thickness is 3.7 mm (A), tumour
width is 9.4 mm (B), E – epidermis, D – dermis.

be available for cosmetic-aesthetic purposes, e.g. evaluation of


actinic skin damage, localizing implants, and therapy control for
keloids and haemangiomas.2,3,43
Diseases with skin sclerosis on ultrasonographic evaluation usu-
ally present as a regular increase of dermis echogenicity as the
result of the accumulation of collagen fibres in this region and
increase of the skin thickness.44,45 Cosnes et al. using transducer of
13 MHz frequency in scleroderma plaque detected a characteristic
Figure 2 Nodular basal cell carcinoma. (a) Clinical image. (b)
dense image resembling a flattened ‘yo-yo’ with undulations of the
Ultrasonic image of 14 MHz shows heterogeneous structure with dermis, disorganization, loss of thickness and thickened hypere-
poorly defined margins, tumour thickness is 2.5 mm (A), tumour chogenic bands in the subcutis.46
width is 9.4 mm (B), E – epidermis, D – dermis. (c) Histological In general, echogenicity is decreased in dermal oedema, but
image shows histological measurement of tumour thickness, there are marked differences in the distribution of the low echo-
which is 2.8 mm (haematoxylin–eosin stain, original magnification
·20).
genic region in various diseases. In lipodermatosclerosis, a decrease
of echogenicity is noted mainly in the subepidermal region,

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JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
Principles of high-frequency ultrasonography 381

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JEADV 2011, 25, 375–382 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology

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