Spectral emissivity measurements of human skin—A new method for the early detection of cancer?

Infrared Phys. Vol. 24, No. 2i3, pp. 353-358, P&ted in Great Britain. All rights reserved

SPECTRAL

1984 Copyright

EMISSIVITY

SKIN-A

NEW

MEASUREMENTS

METHOD

DETECTION

for Social Medicine

and Occupational

OF HUMAN

FOR THE EARLY

OF CANCER?

W. FOLBERTH Institute

0020~0891/84 $3.00 + 0.00 Press Ltd

C:I 1984 Pergamon

and G. HEIM

Health,

University

of Heidelberg,

6900 Heidelberg,

F.R.G.

(Receiwd 9 September 1983) Abstract-A Michelson interferometer has been modified to measure the spectral emissivity E(k) of living human skin in the spectral range k = 250-430 cm-’ (i.e. 23.340 pm). In order to investigate nonorganspecific changes in the general condition of a patient the ball of the right thumb has been chosen as the measuring point. The radiation intensity of the skin is compared with that of a blackbody of the same temperature, using the quotient the spectral emissivity is determined. The spectral emissivity of the skin was measured in both the cancer patients (n = 14) and the control group (n = 14). The standardized emissivity curves were examined with regard to their most important structural characteristics. First results show significant differences: in the control group the curves of E(k) are very smooth and over the total spectral range examined close to E = 1. In contrast, the emissivity curves of the cancer patients show great fluctuations and the integral value of E(k) differs widely from E = 1. By means of a discriminant analysis, 92.86% of the cases were correctly classified. These results seem to indicate correlations between the disease stage of a person and the characteristics of the spectral emissivity E(k).

INTRODUCTION

The increasing number of patients suffering from cancer is a dramatic challenge for medical science. In spite of intensive research there have been to date very few promising treatment approaches. However, it is known that the earlier the diagnosis of cancer is made, the greater the chances of successful treatment. Therefore, preventive medicine, in its endeavor towards the development on noninvasive, sensitive diagnostic methods for the early detection of cancer, is becoming increasingly more important. Until recently the main interest has focused on the development of local, morphological diagnostics with the aim of tracing the carcinoma in its earliest possible stage. Above all, the results obtained in immunology research suggest that cancer has to be regarded as a systemic disease of the whole organism, whereby the formation of a tumor represents only the end product of a long chain of nonspecific, functional disorders. (‘z) This premise indicates that veritable early detection of cancer requires the development of nonspecific diagnostics of systemic changes which indicate a cancer risk before a tumor has developed. From this point of view further investigation of the IR radiation emitted by the skin is of increasing importance. The thermal diagnostic procedures developed up to now have almost exclusively been confined to the measurement or the visual description of the integral radiation intensity, for example IR-camera”’ or “thermoregulation diagnostics”.‘4) However, the diagnostic utilization of pathologically-related variations in the spectral emission characteristics has not yet been examined. The aim of this paper is to find correlations between the patient’s disease stage and the course of the spectral emissivity E(k) of the skin. The measurable spectral range for medical use has been very limited. According to Planck’s radiation law the spectral radiant emittance M(i) for a blackbody at T = 310 K has a maximum at 1. = 9.4 pm and decreases sharply on both sides of the peak. Therefore all thermal diagnostic procedures developed up to now measure within the range ,I = 5-20 pm. The first spectral measurements of the human skin were also restricted to this spectral region.(5 ‘) The limited sensitivity of the monochromator systems used for these measurements and the low intensity of human IR radiation are the reasons for the restriction of the measuring range to wavelengths of 5-20 pm. It has become apparent that the emissivity of human skin in this range is very similar to that of a blackbody and is of the order of E = l.(‘-‘) However, in female patients with advanced mamma 353

354

W. FOLBERTH and G. HEIM

carcinoma the spectral emissivity measured over the carcinoma is reported to reach levels as high as E = 1.31.(*) Indications of pathologically-related variations within the FIR range i. > 20 LLm had been assumed in cancer patients but were only of a qualitative nature because of the inadequate measuring technique. (9)Consequently the examination of the FIR range requires a more sensitive measuring method considering the fact that about 20% of the total radiation intensity falls into the long wave band 2 > 20 pm. Because of its special advantages (“Jacquinot’s advantage”. “Fellgett’s advantage”) FTS seems appropriate for investigations in the FIR range.

EXPERIMENTAL

DETAILS

Spectrometer system A Michelson interferometer (System MK3 GRUBB PARSONS) has been modified to determine the spectral emissivity E(k) of living human skin (Fig. 1). A beam-splitter of polyethylene terephtalate (thickness d = 6.25 pm) is used to investigate the spectral region k = 2.5&430 cm-‘. The interferometer unit is evacuated at a pressure p = 10m2 mbar to avoid absorptions from the air. High density white polyethylene (PE) proves to be the most suitable vacuum window material because of its favorable transmission characteristics in the FIR region as well as its high mechanical stability. The PE filter placed at the entrance aperture has a thickness of d = 1.5 mm and a diameter of d = 19 mm, the thickness of the second PE filter at the detector unit is d = 2 mm. For reasons of signal amplification (by a lock-in amplifier) the incident radiation is chopped by a polished Al-blade at a frequency of 17 Hz. The dependence of the intensity reaching the detector on the path difference of the moved mirror. Z(x), is measured by a Golay detector. The digitalization of this double-sided interferogram I(x) is done by an analog-digital converter (g-bit ADC) and then stored in a Z80-microcomputer. The

lnterferogrom

I dlgitolizad

I(x)

I

Beam

-spll

ldz6.25

tter

MICHELSON

LL__ Spectral

emisslvity

’

IJ-m)

INTERFEROMETER

-I

Elk)

Fig. 1. Schematic

diagram

of the Fourier

spectrometer.

Spectral

emissivity

measurements

of human

skin

355

Fourier analysis [fast Fourier transformation (FFT)] by the 280 computer yields the spectral radiant emittance M(k). After the measurement of 512 data points the spectral resolution, Ak = 1/2AX, is found to be Ak = 7.8 cm-‘. Measured

skin area

For the “thermoregulation diagnostics” developed at our institute measuring points on the extremities are used for estimating the general condition of a patient. These measuring points are located on the nonorgan-specific dermatome C6. (‘O)For this reason, the ball of the right thumb which is on the same dermatome has been chosen as the measuring point for the spectral investigations discussed here. Blackbody

standard

Before and after the spectral measurement the temperature at the ball of the thumb is measured with a calibrated Thermophil IR thermometer (Type Ultrakust M202). In a comparative measurement the radiation intensity of the skin is compared with that of a blackbody radiator at the same temperature. The construction of the blackbody is shown in Fig. 2. The inner surface of the cavity is blackened by a special coating (3M velvet coating). The whole cavity is surrounded by water at a constant temperature (AT < 0.02 K). The diaphragm has a diameter of 19 mm. The geometrical layout only allows radiation from the cone to enter the interferometer. According to Ref. (11) the vertical-placed blackbody has the emissivity E = 0.999. Cancer patients

and control persons

Measurements on 14 patients have been performed. All of them eligible because of a histologically ensured carcinoma: 12 cases of breast carcinoma, 1 case of ovarian cancer, 1 case of testicular cancer. All patients have been under medical treatment for several years, the average age is 47 years. The control group consists of 14 subjectively healthy female persons with an average age of 27 years. None of them showing any findings of a carcinoma. To warrant a statistical analysis the procedural rules of all measurements have been kept constant. RESULTS A Fourier analysis of the measured Z(x) data yields the spectral radiant emittance M(k). Typical curves of M(k) for a control person and a cancer patient are shown in Figs 3a and 3b. Using the ratio M(k &son M(k)blackbody

Blackened

Fig. 2. Layout

of the blackbody.

W. FOLBERTH and G. HEIM

356

3

2 2 r

(al 400 -

s 6

300

2 0 5 6 : E L ; x v1

I :‘i--I-

-a’

_ .“,( ,‘““,\ ”

/’

1..

200 100 -

\ \

__j

,-. 0

100

200

300

k(Cnl

-,

400

0

500

-L_.-.._ 100

300

200

1

kicm

Fig. 3. Spectral radiant emittance M(k) of the ball of the right thumb blackbody at the same temperature. (a) Control person, ----blackbody ---blackbody at 35 ‘C.

(-)

-1

400

500

i

compared with that of a at 32’C. (b) Cancer patient.

the spectral emissivity E(k) is calculated. Figure 4 shows these two ratio curves. There arc significant differences between the cancer patients and the control group in the integral value of E(k) and in the fluctuations of the emissivity curve over the total spectral range investigated. For further analysis E(k) is divided into smaller spectral regions, bearing in mind the working range of the interferometer. Several parameters are computed: -mean value (MV) of E(k) over several spectral regions; -standard deviation (SD) and variance (VR) of E(k) for the corresponding regions as a criterion of the fluctuation; -combinations of mean value, standard deviation and variance as variables for calculating a discriminant analysis. The spectral region k = 250-430 cm-’ appears to be the most significant to use in the discriminant analysis (5% level). Figures 5a and Sb show plots of the mean value E(k) and the standard deviation of all cases under investigation. By a univa~ate analysis it becomes evident that the variable Var 1 = absfl

- MV) + SD

is significantly different for both groups at the 0.01% level (F-value multivariate statistic shows that by considering the variable

= 22.10). Computation

of a

Var 2 = (1 - MV)2 + VR the group selection can be improved (see Table 1). The discriminant function D is calculated by using Var I, Var 2 and the corresponding canonical coefficients. For clearer presentation D is converted into a discriminant SCORE for each person. whereby the scale of the SCORE is chosen between 0 and 100. Herewith the mean SCORE of the control persons yields 38.7 in contrast to that of 59.6 for the cancer patients. The resuks of the discriminant analysis are shown in Figs 6a and 6b. The percentage of correct group classification is 92.86% according to the clinical diagnosis, whereby 85.7’!,, of the cancer patients (true positive) and 100% of the control persons are correctly ciassified (true negative). As Table I. Data for the ran% k =250_430cm-

Parameter value E(k) (MV) -~ Standard deviation (SD) Variance (VR) Var 1 Var 2

&n

Control group

Cancer patients

1.004 *0.0410.061 kO.015 0.0039 + 0.00 IX 0.095 + 0.022 0.0055 + 0.0019

0.943 0.094 0.0099 0.228 0.0359

* * + + ;

0. I56 0.034 0.0078 0 IO3 0.0337

357

Spectral emissivity measurements of human skin 12

-

1.0

-----I_

Control

person

;; I,

0.0

-

f G .r E D

0.6

-

z L

0.4

-

02

-

A

x b-J

0

I

I

I

I

100

200

300

400

k(

I 500

cm-‘1

Fig. 4. Spectral emissivity E(k) of a control person and a cancer patient. Spectral range under investigation: k = 25&430cm-‘.

can be seen in Fig. 6a the SCORE values of the control group show a nearly normal frequency distribution, whereas the SCORE values of the cancer patients are spread over a wide range. DISCUSSION

First of all the dependence on age of the measured data has been investigated. By correlating all the variables of a case with the corresponding age a standardization of age had been made, However, it appears that there was no significant dependence on age. The broad SCORE distribution indicates inhomogeneity of the cancer group. This is likely to be due to the very different courses of disease: -all patients had been operated on and treated at the time of the investigation, but method and period of treatment was different; -at the time of the operations there were different stages and localizations of the tumors. Because of the small number of cases all results have to be considered as provisional. Nevertheless the emissivity curves show some clear trends. The integral value of E(k) for control persons is close to E = 1, whereas for cancer patients E(k) differs markedly from E = 1. It is notable that some patients show values up to E = 1.15. This means a greater radiation intensity in the region k = 250-430 cm-’ than the blackbody radiation at the same temperature. However, it must be considered that the temperature adjustment is carried (b) at-

n

7-

6 fz B r;

62

5

z

5

4 3

z" 2

1072 0.65 Mean

t

0861

079 value

0.93 (MV)

10

II.14 1.07 of

1

0

Elk)

Fig. 5a. Mean value of E(k) in the region k = 250-430 cm-’ of all persons investigated: •J controls; I cancer patients.

t

0.05

0.03

1.21

f 009 0.07

Standard

t 0 13 0.11

f 0.17 0.15

deviation

I SD)

Fig. Sb. Standard deviation of E(k) in the region of all persons investigated: q controts; q cancer patients.

k = 250430 cm-’

W. FOLBERTH and G. HEIM

358

Fig. 6a. Distribution of the discriminant all persons (0. controls; q, cancer

SCORE patients).

of

Predicted group membership Actual group Cancer

No of cases 14

Control

14

Cancer

control

(8G%)

(I 4.:%,

&,

(1 G%,

92.86% of cases correctly classified! Fig. 6b. Results

of the discriminant

analysis.

out within the working range of the thermometer, /1 = 5515 pm (i.e. 660-2000 cm-‘), where the emissivity of normal human skin is almost E = 1. The emissivity curves show local fluctuations which can be quantized by calculating the standard deviation and variance. It appears that on average cancer patients show greater fluctuations in E(h-) than control persons (see Fig. 5b). This seems to suggest that differences in the course of E(k) indicate the existence of pathological processes inside the organism. To investigate whether these differences in E(k) are correlated to the development of a tumor, measurements on patients with other diseases need to be performed. Results of such work will be published shortly. CONCLUSION Based on these results follow-up studies are in progress to show whether correlations exist between the therapeutic results and the SCORE. More cancer patients with defined disease stages have to be investigated to substantiate these results. For the purpose of follow-up studies measurements before and after an operation are necessary. The examination of organ-specific indications requires measurements on several other skin areas. In this way it may be possible to develop a noninvasive method for the early detection of cancer. Acknowledgemenls~The authors would like to thank Th. Zapf, Institut fur Sozial-und Arbeitsmedizin, group of the Physikalisches Institut Heidelberg for their aid in setting up the computing system. Thanks also due to IBM Deutschland for tinancial support.

and the electronic

REFERENCES 1. Perger F., II&n. med. Wschr. 128, 31 (197X). 2. Pischinger A., Das System der Grundregulution. Haug, Heidelberg, F.R.G. (1975). 3. Gorse MPditerr. Mid. 216, (1972). 4. Heim G. and Blohmke M., Diagnose ohnr Ri.siko~~Thermoregulutionsdiagnosfik UMSCHAU 81 18, 562 (198 I ). 5. Hardy J. D., J. c/in. Inoest. 13, 605 (1934). 6. Buchmiiller K., Pfriigers Arch. ges. Physiol. 272, 360 (1961). 7. Steketee J., Physics Med. Biol. 18, 686 (1973). 8. Patil K. D. and Williams K. L., Non-ionizing Radiu/. 1, 39 (1969). 9. Rost A. and Reeh J. J., Thermoregulutionsdiagnostik, p. 74. MLV ulzen, Berlin, F.R.G. (1980). II). Hansen K. and Schliack H., Segmentule Innrrcalion-ihrr Bedeutung in Kiinik und Pturis. Thieme, Stuttgart, F.R.G. (1962). Il. Engel J.-M., Flesch U. Stiittgen G.. Thermologiwhe Mrssmefhodik. Notamed, Baden-Baden, F.R.G. (19X3).