terahertz spectroscopy of pigmentary skin nevi in vivoteratech.ru/uploads/os1193.pdf · plastic...

404

ISSN 0030-400X, Optics and Spectroscopy, 2015, Vol. 119, No. 3, pp. 404–410. © Pleiades Publishing, Ltd., 2015.Original Russian Text © K.I. Zaitsev, N.V. Chernomyrdin, K.G. Kudrin, I.V. Reshetov, S.O. Yurchenko, 2015, published in Optika i Spektroskopiya, 2015, Vol. 119, No. 3, pp. 430–437.

Terahertz Spectroscopy of Pigmentary Skin Nevi in VivoK. I. Zaitseva, b, N. V. Chernomyrdina, c, K. G. Kudrina, b,

I. V. Reshetovb, c, and S. O. Yurchenkoa, b

a Bauman State Technical University, Moscow, 105005 Russiab Institute for Professional Training, Medical Biological Agency of the Russian Federation, Moscow, 125371 Russia

c Gertsen Scientific Research Oncological Institute, Moscow, 125284 Russiae-mail: [email protected], [email protected], [email protected], [email protected], [email protected]

Received March 30, 2015

Abstract—Pigmentary skin nevi are studied in vivo using terahertz pulsed spectroscopy. Dielectric parametersof healthy skin and dysplastic and nondysplastic nevi are reconstructed and analyzed. The fact that complexpermittivities of the samples substantially differ in the terahertz spectral range can be used for early noninva-sive diagnostics of dysplastic nevi, which are precursors of melanoma (the most dangerous skin cancer). Amethod is proposed to identify various dysplastic and nondysplastic nevi using the analysis of terahertz dielec-tric characteristics. It is demonstrated that terahertz pulsed spectroscopy is promising for early noninvasivediagnostics of dysplastic nevi and melanomas of the skin.

DOI: 10.1134/S0030400X1509026X

INTRODUCTIONThere has been considerable recent interest in the

application of the terahertz (THz) pulsed spectroscopyas a promising tool in the noninvasive and intraopera-tive medical diagnostics of human diseases [1, 2].

The progress that has been made in THz pulsedspectroscopy is related to the study of the photocon-ductivity (photoswitching) in semiconductors underthe action of ultrashort optical laser pulses [3]. Thedevelopment of such a spectroscopic technique isrelated to advent of high-stability femtosecond lasersand the new methods for pulse generation and detec-tion [4–7]. The THz spectroscopy makes it possible tostudy THz dielectric and THz optical characteristicsof media [8–14] and inner structure of dielectricobjects (THz tomography) [15–18]. The broadbandTHz radiation of a pulsed spectrometer is low-powernonionizing radiation that does not negatively affectbiological objects [19]. THz pulse spectrometers canbe used for diagnostics of cancer of the oral cavity [20],skin [21–26], and intestinal tract [27]. The THz spec-troscopy and imaging are used for intraoperative diag-nostics of breast cancer [28]. The method has alsobeen employed for diagnostics of demineralization oftooth enamel [29] and diagnostics of liver cancer andcirrhosis [30, 31]. Therapy of skin cancer using THzelectromagnetic radiation was discussed in [32]. How-ever, that there are insufficient data on several bio-medical applications of THz pulsed spectroscopyneeds to be noted. One of them is diagnostics of dys-plastic skin nevi. The topicality of the problem isrelated to the fact that dysplastic nevi are precursors of

melanoma [33], which is the most dangerous skin can-cer [34].

The purpose of this work is analysis of diagnosticsof dysplastic skin nevi with the aid of the THz pulsedspectroscopy. Several problems are solved for this pur-pose. A method to solve an inverse problem of thereconstruction of the THz dielectric parameters ofbiological tissues in vivo is proposed. Analysis of theTHz dielectric parameters is used for early differentialdiagnostics of melanoma and dysplastic and nondys-plastic nevi.

DYSPLASTIC NEVI

Dysplastic skin nevi morphologically differ fromnondysplastic nevi. With a relatively high probability,dysplastic nevus can be transformed into skin mela-noma [33], so that dysplastic nevi are classified as pre-cursors of skin melanoma. Figure 1 presents the clinicphotographs of pigmentary skin nevi: images (a) and(b) correspond to nondysplastic (common) and dys-plastic nevi, respectively.

Several existing methods can be used for noninva-sive diagnostics of dysplastic nevi. Note the mostwidespread dermatoscopy [35] (including digital andepiluminescence dermatoscopy) and systems for com-puterized screening of skin [36]. The topicality of thedevelopment of new methods for noninvasive diag-nostics of dysplastic nevi and early diagnostics of mel-anoma is proven by statistical data on morbidity andmortality related to skin cancers.

THE INTERNATIONALYEAR OF LIGHT 2015

OPTICS AND SPECTROSCOPY Vol. 119 No. 3 2015

TERAHERTZ SPECTROSCOPY OF PIGMENTARY SKIN NEVI 405

EXPERIMENTAL SETUP

A THz pulsed spectrometer was developed for thein vivo study of the THz dielectric characteristics ofhealthy skin and dysplastic and nondysplastic nevi.Figure 2 shows the scheme of the THz spectrometerthat is similar to the schemes of [12, 17]. The fre-quency range of the setup operation is 0.1–2.5 THz.The spectrometer employs the second harmonic of afemtosecond Er-doped-fiber laser with a radiationwavelength of 780 nm, a mean power of 150 mW, apulse duration of 85 fs, and a pulse repetition rate of60 MHz. Femtosecond laser radiation is used for thegeneration of THz pulses in a photoconductive LT-GaAs antenna and the detection of the waveform of

THz electric field E(t) in the ZnTe electroopticaldetector with a time resolution of 40 fs.

The radiation of laser 1 is incident on beamsplitter 2and is divided into pump I and probe II beams, so thatthe pump intensity is significantly higher. The pumpradiation is focused by lens 3 on the LT-GaAs film ofphotoconductive antenna 4. Each pumping pulsecauses generation of THz radiation, and the voltageacross the photoconductive antenna and, hence, themean power of the THz radiation are modulated at afrequency of 100 kHz. The THz pulses pass throughthe system of mirrors 5, 8, and 9 and silicon beamsplit-ter 13 and are focused on the surface of the sampleunder study using polymethylpentene TPX lens 26.The reflected THz pulse passes through beamsplitter

Fig. 1. Photographs of (a) nondysplastic and (b) dysplastic nevi of the skin in vivo.

(a) (b)

10 mm 10 mm

Fig. 2. Scheme of the setup for the study of the dielectric characteristics of skin tissues in vivo: (1) femtosecond Er-fiber laser(operating at the second harmonics); (2) and (13) beamsplitters; (3), (15), and (26) lenses; (4) photoconducting antenna; (5) and(19) off-axis parabolic mirrors; (6)–(12), (14), (16), and (18) mirrors; (17) polarizer; (20)–(23) electrooptical detector of theTHz field ((20) ZnTe crystal, (21) quarter-wave retardation plate, (22) Wollaston prism, and (23) balanced photodetector); (24)lock-in amplifier; and (25) PC. Three signals are measured for the reconstruction of permittivity of skin in vivo: (a) signal Erreflected from crystalline quartz plate (27), (b) signal Em reflected from gold-coated reference mirror (28) located behind quartzplate (27), and (c) signal Es reflected from sample under study (29) located behind quartz plate (27).

1

67

2 34

8

5

9

~V

10

2423

22

λ/4 ZnSe

21 20(c)

(b)

(a)

25

14

15 17

18

29

f ′

28

2726

1312

19

16

11

I

II

406


ZAITSEV et al.

13 and mirrors 12 and 19 and is incident on electroop-tical detectors 20–23 simultaneously with the probefemtosecond laser pulse that passes through delay line7–11; mirrors 14, 16, and 18; lens 15; and polarizer 17.The electrooptical detector is based on ZnTe crystal20, quarter-wave retardation plate 21, Wollaston prism22, and balanced quadratic photodetector of opticalradiation 23. When the THz and optical beams simul-taneously propagate in the ZnTe crystal, the linearpolarization of the optical radiation is transformedinto polarization with a relatively low ellipticity, so thatthe THz electromagnetic field serves as the controlfield of the electrooptical cell. The quarter-wave retar-dation plate provides transformation of the low-ellip-ticity or linear polarization into elliptical or circularpolarization. The Wollaston prism spatially separatesthe orthogonally polarized components of the opticalradiation, and, then, the components are detected bythe quadratic photodetector. The intensity differenceof the orthogonally polarized components of the fem-tosecond laser radiation is proportional to the THzfield strength at the given delay of the probe opticalpulse relative to the THz pulse. A variation in the delaytime of the probe pulse provides time-gating of theTHz field and makes it possible to measure fieldstrength E(t) at different time moments.

Figure 2 illustrates the detection of signals neededfor the solution of the inverse problem of THz pulsedspectroscopy related to the reconstruction of the THzdielectric characteristics of biological tissues in vivo.Crystalline quartz plate 27 with a thickness of 1 mm isused to fix the tissue under study in the THz spectro-scopic system. For each sample, we measure three sig-nals: signal Er = Er(t) that is reflected only from thequartz plate (a), signal Em = Em(t) that is reflectedfrom gold-coated mirror 28 placed behind the quartzplate (b), and signal Es = Es(t) that is reflected fromsample under study 29 located behind the quartz plate(c). Let , , and bethe Fourier transforms of signals Er, Em, and Es (ν isthe frequency of electromagnetic radiation). The sig-nals contain the THz pulse that is reflected from theair–quartz interface and the THz pulses that arereflected from the glass–air (a), glass–mirror (b), andglass–sample (c) interfaces. The first pulse (reflectedfrom the quartz surface) is identical for signals Er, Em,and Es and, hence, can be used to calculate commonzero time. Signals Er, Em, and Es additionally containsatellite THz pulses owing to multiple reflections ofthe THz pulse in the quartz window. The satellitepulses are taken into account in the solution of theinverse problem to increase the reconstruction accu-racy of the THz dielectric characteristics of the samplein vivo [11, 12, 25, 37, 38].

( )r rE E= ν� � ( )m mE E= ν� � ( )s sE E= ν� �

RECONSTRUCTION OF PERMITTIVITYThe proposed method for the study of THz dielec-

tric characteristics in vivo makes it possible to recon-struct THz complex permittivity , such that

, where and are thereal and imaginary parts of the complex permittivity.The inverse problem is solved using the minimizationof the error functional:

(1)

where and are theexperimental and theoretical response functions and|…| and φ […] are the operators of magnitude andphase, respectively.

The experimental response function is given by

. (2)

The theoretical response function takes intoaccount the satellite pulses in the signals of the THzspectrometer and is written as

, (3)

where is the operator thatdescribes the Fresnel reflection at the interface of themth and kth media:

. (4)

Subscripts m, k = 0, 1, 2, and 3 correspond to air, crys-talline quarts, biological sample, and gold mirror,respectively. Operator describes thetransmission of the THz radiation through crystallinequartz with thickness l and is determined using theBouguer–Lambert–Beer law:

, (5)

where c = 3 × 108 m/s is the speed of light in vacuum.In expressions (3)–(5), permittivities of air and crys-talline quartz and , effective permittivity of themirror , number of satellite pulses N, and thicknessof quartz plate l are a priori known quantities andpermittivity of sample is found from expres-sion (1).

Several parameters affect the reconstruction accu-racy of the THz dielectric characteristics: noise in thesignals of the THz spectrometer, nonuniformity of thespectral sensitivity of the spectrometer, resonances ofthe THz pulse in the quartz plate, and fluctuations ofthe positions of the quartz plate in the spectrometer

( )ε = ε ν� �

' ''iε = ε − ε� ( )' 'ε = ε ν ( )'' ''ε = ε ν

[ ][ ] [ ] 22

exp exp

arg min ,

,th thH Ht H H

εε = Φ

Φ = − + φ − φ�

�

� � � �

( )exp expH H= ν� � ( )th thH H= ν� �

expS r

m r

E EHE E

−=−

� �

�

� �

( )( )

1 1 212 10 12 10 10 11

1 1 213 10 13 10 10 11

N j j j j

jth N j j j j

j

R R R R R PH

R R R R R P

+ +=

+ +=

− + −=

− + −

∑∑

� � � � � �

�

� � � � � �

( ), ,mk mk m kR R= ν ε ε� �

� �

k mmk

k m

R ε − ε=ε + ε� �

�

� �

( )1 1 1, ,P P l= ν ε� �

( )1 12expP i l

cπν= − ε�

�

0ε� 1ε�3ε�

2ε = ε� �



due to displacements of the sample (patient effect). Inthis work, we find the reconstruction errors of the THzdielectric characteristics using the methods of numer-ical simulation (a similar approach is used in [11, 17]).To determine the errors, we solve the problem of scat-tering of the THz pulse by sample with known permit-tivity and simulate the signal detection in the THzspectrometer with allowance for the above negativeeffects. Disturbed signals are used to solve the inverseproblem, and THz dielectric characteristics of thesample are reconstructed.

Comparison of original and reconstructed dielectric characteristics makes it possible to calculatethe errors of the solution to the inverse problem. Theanalysis of the stability of reconstruction of the THzdielectric characteristics in vivo with respect to severalfactors and detailed estimation of the reconstructionaccuracy of the THz dielectric characteristics of bio-logical tissues in vivo under typical experimental con-ditions are beyond the scope of this work and will bepublished separately. To increase the stability of theproposed method for the reconstruction of the THzdielectric characteristics with respect to the digitalnoise of signals Er, Em, and Es, we employ the noise fil-tering in the wavelet domain [39, 40].

We have tested the proposed method for the recon-struction of dielectric characteristics. Figure 3 showsthe original results of the in vivo study of the healthyskin and the known spectroscopic results of [32]. Wepresent THz refractive index n = n(ν) and THz

initε�

recε�

initε� recε�

absorption coefficient α = α(ν), which are related tothe complex permittivity:

(6)

where is the complex refractive index. Evi-dently, the results of this work are in good agreementwith the known experimental results accurate to thereconstruction errors of the refractive index andabsorption coefficient.

IN VIVO THz SPECTROSCOPY OF PIGMENTARY NEVI

The proposed method is used to study pigmen-tary skin nevi of four patients in vivo. For eachpatient, we reconstruct permittivities of healthy skin

and dysplastic and non-dysplastic (common) nevi. The mea-surement spectral interval is limited due to several rea-sons. The nevi sizes limit the spectral interval at lowfrequencies ν > 0.3 THz due to diffraction limit of res-olution upon focusing of the THz beam on the surfaceof object. The scattering of the THz radiation by skininhomogeneities limits the spectral interval at highfrequencies ν < 1.0 THz, since the high-frequencycomponents of the pulse are strongly scattered (incomparison with the low-frequency components)[24]. Thus, the in vivo THz spectroscopy of the skinpigment neoplasms can be performed in a frequencyinterval of 0.3–1.0 THz. For such an interval, weobtain reproducible spectral characteristics of the pig-ment neoplasms.

Figures 4a–4c present the spectroscopic results forhealthy skin and dysplastic and nondysplastic nevi ofthe first patient, which are represented as real , ,and and imaginary , , and parts of thecomplex permittivity and Cole–Cole diagrams [41],

, , and . Figures 4d–4f, 4g–4i,and 4j–4l present the corresponding results of the sec-ond, third, and fourth patient, respectively. Thedielectric characteristics of the healthy skin and dys-plastic and nondysplastic nevi differ in a high-fre-quency interval of 0.85 < ν < 0.95 THz. Note signifi-cant differences of the slopes of curves , , and and Cole–Cole diagrams , , and .

The penetration depth of the THz radiation for skinin vivo is relatively small (several hundreds ofmicrons), so that the spectroscopic study makes itpossible to reconstruct the THz dielectric characteris-tics of the upper skin layer (epidermis) [42]. Theexperimental results may substantially depend on thestructure of epidermis, especially, thickness and struc-ture of stratum corneum [16]. The THz complex per-mittivity of biological tissues of normal and patholo-

, ,2

cn n n i= ε = − απν

��

( )n n= ν� �

' ''S S Siε = ε − ε� ' ''D D Diε = ε − ε�

' ''N N Niε = ε − ε�

'Sε 'Dε'Nε ''Sε ''Dε ''Nε

'' '( )S Sε ε '' '( )D Dε ε '' '( )N Nε ε

'Sε 'Dε 'Nε'' '( )S Sε ε '' '( )D Dε ε '' '( )N Nε ε

Fig. 3. Comparison of the experimentally measured refrac-tive indices and absorption coefficients of the skin in vivoin the THz frequency range: (squares) and (triangles)results of this wok and (solid line) and (dashed line) well-known results of [32].

3.5n(ν) α(ν), mm−1

20

15

10

5

0

3.0

2.5

2.0

1.5

1.01.41.21.00.8

ν, THz0.6

12

0.4

,,

0.2

408


ZAITSEV et al.

gical skin is described using single or double Debyemodels [41, 43–45]:

, (7)

where j is the term number in the Debye model, N isthe number of terms (number of relaxation processes),ε∞ and Δεi are the parameters of the Debye model, andτi are the relaxation times. The differences of the THzdielectric characteristics of tissues (Fig. 4) are primar-

11 2

Ni

iii∞

=

Δεε = ε ++ πντ∑�

ily due to the difference of the relaxation processesthat are responsible for the dielectric characteristics ofthe healthy skin and dysplastic and nondysplastic nevi.

SELECTION OF PRINCIPAL COMPONENTSTo illustrate the search for the differences of the

dysplastic and common nevi of the skin based on theTHz characteristics, we implement the principal com-ponent analysis [23, 24]. It may seem that the relax-ation parameters of Debye model (7) are convenient

Fig. 4. Spectral curves of permittivities of (solid lines) healthy skin , (dashed lines) dysplastic nevi , and (dashed-and-dottedlines) nondysplastic nevi for four patients: (a), (d), (g), and (j) real parts and (b), (e), (h), and (k) imaginary parts ofcomplex permittivity and (c), (f), (i), and (l) Cole–Cole diagrams based on the THz dielectric characteristics of tissues.

3.5ε' ε''

3.0

2.5

2.0

1.5

1.0

1.0

(а)no. 1

0.90.80.70.60.50.40.3

3.5

3.0

2.5

2.0

1.5

1.01.0

(b)

0.90.80.70.60.50.40.3

ε''

4

3

2

1

(c)

3.53.02.52.0

3.5

3.0

2.5

2.0

1.5

1.0

1.0

(d)no. 2

0.90.80.70.60.50.40.3

3.5

3.0

2.5

2.0

1.5

1.01.0

(e)

0.90.80.70.60.50.40.3

4

3

2

1

(f)

3.53.02.52.0

3.5

3.0

2.5

2.0

1.5

1.0

1.0

(g)no. 3

0.90.80.70.60.50.40.3

3.5

3.0

2.5

2.0

1.5

1.01.0

(h)

0.90.80.70.60.50.40.3

4

3

2

1

(i)

3.53.02.52.0

3.5

3.0

2.5

2.0

1.5

1.0

1.0ν, THz ν, THz ε′

(j)no. 1

0.90.80.70.60.50.40.3

3.5

3.0

2.5

2.0

1.5

1.01.0

123

(k)

0.90.80.70.60.50.40.3

4

3

2

1

(l)

3.53.02.52.0

Sε� Dε�Nε� 'ε ''ε

ε� ( )'' 'ε ε



for the construction of the principal component space.However, the limited spectral interval does not make itpossible to correctly solve the problem of estimation ofthe parameters of relaxation processes (relaxationtimes τ and dielectric constants ε∞ and Δεi) in themedium using the experimental data. The featurespace for diagnostics can be constructed using theanalysis of the signals of the THz spectrometer in timedomain (the analysis of the pulsed response of themedium under study [21, 22]) or the spectral data(spectral curves of the reflection and absorption coef-ficients in the THz spectral range [11, 44] or THz per-mittivity of tissues [24, 43]).

Figure 4 clearly shows significant differences of thecharacteristics of samples on the Cole–Cole dia-grams. For the recognition of the dysplastic and non-dysplastic nevi, we may use the slope of the Cole–Cole diagram of the complex permittivity:

, (8)

where Δν is the working frequency interval (0.3–0.95 THz) and subscripts D, N, and S correspond tothe dysplastic and nondysplastic nevi and healthy skin,respectively. The feature that makes it possible to finddifferences is introduced as

. (9)

( )''

/ // /

' / /

1 arctan D N SD N S

D N S

dd

dΔν

⎛ ⎞εθ = ν ν⎜ ⎟⎜ ⎟Δν ε⎝ ⎠

∫

/ /D N D N SΔθ = θ − θ

Note that the slopes of the Cole–Cole diagrams ofthe dysplastic and nondysplastic nevi are normalizedby the slope of the diagram of the healthy skin. Thenormalization is necessary, since substantially differ-ent THz dielectric characteristics are obtained for dif-ferent fragments of the healthy skin or differentpatients [24]. Therefore, the spectral characteristics ofthe pigmentary skin neoplasms must be comparedwith the characteristics of the healthy skin from thesame fragment of the patient’s body.

Figure 5 shows the results of calculation of feature (9)for recognition of dysplastic and nondysplastic nevi forfour patients. The calculations are based on the abovedielectric characteristics (Figs. 4c, 4f, 4i, and 4l). Thedashed line in Fig. 5 shows the selection threshold forthe dysplastic and nondysplastic nevi. Thus, we provethe efficiency of the proposed approach in the differ-ential diagnostics of pigmentary nevi and show thatthe THz pulsed spectroscopy is promising for earlynoninvasive diagnostics of melanoma and its precur-sors.

CONCLUSIONSTHz pulsed spectroscopy is used in the study of

pigmentary neoplasms of the skin (dysplastic andnondysplastic nevi). The THz dielectric characteris-tics of the healthy skin and dysplastic and nondysplas-tic nevi are reconstructed for four patients. It isdemonstrated that the THz dielectric characteristicsof normal tissues differ from the characteristics ofpathological tissues. Such differences can be used forrecognition of dysplastic and nondysplastic nevi.Thus, the THz pulsed spectroscopy is a promisingtool for the early noninvasive diagnostics of mela-noma and its precursors.

ACKNOWLEDGMENTSThis work was supported by the Russian Science

Foundation, project no. 14-15-00758.

REFERENCES1. E. Pickwell and V. P. Wallace, J. Phys. D: Appl. Phys.

39 (17), R301 (2006).2. S. Fan, Y. He, B. S. Ung, and E. Pickwell-MacPher-

son, J. Phys. D: Appl. Phys. 47 (37), 374009 (2014).3. D. H. Auston, Appl. Phys. Lett. 26 (3), 101 (1975).4. D. H. Auston and P. R. Smith, Appl. Phys. Lett. 43 (7),

631 (1983).5. L. Xu, X.-C. Zhang, and D. H. Auston, Appl. Phys.

Lett. 61 (15), 1784 (1992).6. X. Lu and X.-C. Zhang, Phys. Rev. Lett. 108 (12),

123903 (2012).7. A. V. Borodin, N. A. Panov, O. G. Kosareva, V. A. An-

dreeva, M. N. Esaulkov, V. A. Makarov, A. P. Shkuri-nov, S. L. Chin, and X.-C. Zhang, Opt. Lett. 38 (11),1906 (2013).

Fig. 5. Results of calculation of parameter (9) that makes itpossible to select dysplastic and nondysplastic nevi (forfour patients) using the THz dielectric characteristics ofnormal and pathological tissues: (dark columns) dysplastictissues, (light columns) nondysplastic tissues, and (dashedline) threshold for recognition of dysplastic and nondys-plastic nevi.

30⟨Δθ⟩ν

25

20

15

4Patient number

321

2

1

10

410


ZAITSEV et al.

8. L. Duvillaret, F. Garet, and J.-L. Coutaz, Appl. Opt. 38(2), 409 (1999).

9. T. D. Dorney, R. G. Baraniuk, and D. M. Mittleman,J. Opt. Soc. Am. A 18 (7), 1562 (2001).

10. S. Huang, P. C. Ashworth, K. W. C. Kan, Y. Chen,V. P. Wallace, Y.-T. Zhang, and E. Pickwell-MacPher-son, Opt. Express 17 (5), 3848 (2009).

11. K. I. Zaytsev, A. A. Gavdush, V. E. Karasik, V. I. Ale-khnovich, P. A. Nosov, V. A. Lazarev, I. V. Reshetov,and S. O. Yurchenko, J. Appl. Phys. 115 (19), 193105(2014).

12. K. I. Zaytsev, A. A. Gavdush, S. P. Lebedev, V. E. Ka-rasik, and S. O. Yurchenko, Opt. Spectrosc. 118 (4),552 (2015).

13. K. I. Zaytsev, A. A. Gavdush, N. V. Chernomyrdin,N. P. Kruchkov, K. G. Kudrin, P. A. Nosov, V. E. Ka-rasik, and S. O. Yurchenko, J. Phys.: Conf. Ser. 536 (1),012009 (2014).

14. D. M. Mittleman, S. Hunsche, L. Boivin, andM. C. Nuss, Opt. Lett. 22 (12), 904 (1997).

15. K. I. Zaytsev, N. V. Chernomyrdin, and V. I. Alekh-novich, J. Phys.: Conf. Ser. 486 (1), 012010 (2014).

16. Y. Chen, S. Huang, and E. Pickwell-MacPherson, Opt.Express 18 (2), 1177 (2010).

17. K. I. Zaytsev, V. E. Karasik, I. N. Fokina, andV. I. Alekhnovich, Opt. Eng. 52 (6), 068203 (2013).

18. E. V. Yakovlev, K. I. Zaytsev, I. N. Fokina, V. E. Ka-rasik, and S. O. Yurchenko, J. Phys: Conf. Ser. 486 (1),012008 (2014).

19. E. Berry, G. C. Walker, A. J. Fitzgerald, N. N. Zi-nov’ev, M. Chamberlain, S. W. Smye, R. E. Miles, andM. A. Smith, J. Las. Appl. 15 (3), 192 (2003).

20. Y. C. Sim, J. Y. Park, K.-M. Ahn, C. Park, andJ.-H. Son, Biomed. Opt. Express 4 (8), 1413 (2013).

21. R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole,D. D. Arnone, E. H. Linfield, and M. Pepper, J. Inv.Dermatol. 120 (1), 72 (2003).

22. V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flana-gan, R. Pye, J. Cluff, and D. D. Arnone, Brit. J. Der-matol. 151 (2), 424 (2004).

23. S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, andN. Miyoshi, Appl. Phys. Lett. 90 (4), 041102 (2007).

24. K. I. Zaytsev, K. G. Kudrin, V. E. Karasik, I. V. Reshe-tov, and S. O. Yurchenko, Appl. Phys. Lett. 106 (5),053702 (2015).

25. K. I. Zaytsev, K. G. Kudrin, S. A. Koroleva, I. N. Fo-kina, S. I. Volodarskaya, E. V. Novitskaya, A. N. Perov,V. E. Karasik, and S. O. Yurchenko, J. Phys: Conf. Ser.486 (1), 012014 (2014).

26. K. I. Zaytsev, K. G. Kudrin, I. V. Reshetov, A. A. Gav-dush, N. V. Chernomyrdin, V. E. Karasik, andS. O. Yurchenko, J. Phys: Conf. Ser. 584 (1), 012023(2015).

27. C. B. Reid, A. Fitzgerald, G. Reese, R. Goldin, P. Tek-kis, P. S. O’Kelly, E. Pickwell-MacPherson,A. P. Gibson, and V. P. Wallace, Phys. Med. Biol. 56(14), 4333 (2011).

28. P. C. Ashworth, E. Pickwell-MacPherson, E. Pro-venzano, S. E. Pinder, A. D. Purushotham, M. Pepper,and V. P. Wallace, Opt. Express 17 (15), 12444 (2009).

29. E. A. Pickwell, V. P. Wallace, B. E. Cole, S. Ali,C. Longbottom, R. J. Lynch, and M. Pepper, Car. Res.41 (1), 49 (2007).

30. L. Rong, T. Latychevskaia, C. Chen, et al., Sc. Rep. 5,8445 (2015).

31. S. Sy, S. Huang, Y.-X. J. Wang, J. Yu, A. T. Ahuja,Y.-T. Zhang, and E. Pickwell-MacPherson, Phys.Med. Biol. 55 (24), 7587 (2010).

32. L. V. Titova, A. K. Ayesheshim, A. Golubov, R. Rodri-guez-Juarez, R. Woycicki, F. A. Hegmann, andO. Kovalchuk, Sc. Rep. 3, 2363 (2013).

33. M. Arumi-Uria, N. S. McNutt, and B. Finnerty, Mod.Pathol. 16 (8), 764 (2003).

34. R. L. Barnhill, J. A. Fine, G. C. Roush, and M. Ber-wick, Cancer 78 (3), 427 (1996).

35. P. Rubegni, M. Burroni, G. Cevenini, R. Perotti,G. Dell’Eva, P. Barbini, M. Fimiani, and L. Andreassi,J. Inv. Dermatol. 119 (2), 471 (2002).

36. K. G. Kudrin, O. V. Matorin, and I. V. Reshetov, J.Phys: Conf. Ser. 584 (1), 012001.

37. I. Pupeza, R. Wilk, and M. Koch, Opt. Express 15 (7),4335 (2007).

38. K. I. Zaytsev, K. P. Tsapenko, P. A. Nosov, andS. O. Yurchenko, J. Phys: Conf. Ser. 584 (1), 012005(2015).

39. K. I. Zaytsev, N. V. Chernomyrdin, A. V. Gorevoy,N. E. Trofimov, I. N. Fokina, V. I. Alekhnovich,V. E. Karasik, and S. O. Yurchenko, J. Phys: Conf. Ser.486 (1), 012034 (2014).

40. N. V. Chernomyrdin, K. I. Zaytsev, A. A. Gavdush,I. N. Fokina, V. E. Karasik, I. V. Reshetov, K. G. Kud-rin, P. A. Nosov, and S. O. Yurchenko, Proc. SPIE—Int. Soc. Opt. Eng. 9216, 921611 (2014).

41. K. S. Cole and R. H. Cole, J. Chem. Phys. 9 (4), 341(1941).

42. C. Reid, PhD Thesis (2009).43. S. O. Yurchenko and K. I. Zaytsev, J. Appl. Phys. 116

(11), 113508 (2014).44. E. Pickwell, B. E. Cole, A. J. Fitzgerald, M. Pepper,

and V. P. Wallace, Phys. Med. Biol. 49 (9), 1595 (2004).45. E. Pickwell, B. E. Cole, A. J. Fitzgerald, V. P. Wallace,

M. Pepper, Appl. Phys. Lett. 84 (12), 2190 (2004).

Translated by A. Chikishev

terahertz spectroscopy of pigmentary skin nevi in vivoteratech.ru/uploads/os1193.pdf · plastic...

Documents