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Background/purpose: An early diagnosis of cutaneous malignant melanoma is of high importance for good prognosis. An objective, non-invasive instrument could improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies. The aim of this study was to investigate the use of Near infrared and skin impedance spectroscopy in combination as a tool to distinguish between malignant and benign skin tumours.

Methods: Near infrared and skin impedance spectra were collected in vivo on 50 naevi or suspect melanomas prior to excision. Received data was analysed with multivariate techniques and the results were compared to histopathology analyses of the tumours. A total of 12 cutaneous malignant melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study.

Results: The observed sensitivity and specificity of the proposed method were 83% and 95%, respectively, for malignant melanoma.

Conclusions: The results indicate that the combination of near infrared and skin impedance spectroscopy is a promising tool for non-invasive diagnosis of suspect cutaneous malignant melanomas. 

Background/purpose: Near infrared (NIR) and impedance spectroscopy can be used for clinical skin measurements and need to be evaluated for possible confounding factors; (a) are skin conditions of the patient and the subsequent skin measurements influenced by alcohol and/or coffee consumption and (b) are measurements of dysplastic naevi (DN) reproducible over time and significantly different compared to reference skin.

Methods: NIR and skin impedance spectroscopic data were analysed multivariately. In the first study, the skin characteristics of 15 healthy individuals were examined related to body location, gender, individual differences, and consumption of coffee or alcohol. The second study included five patients diagnosed with dysplastic naevi syndrome (DNS). Measurements were taken on DN and reference skin over time.

Results: In the first study, body location and gender had a major influence on measurement scores. Inter-individual skin characteristics and coffee or alcohol effects on skin characteristics were of minor importance. In the second study, it was shown that DN can be differentiated from reference skin and the measurements are stable over time.

Conclusions: Moderate consumption of alcohol and coffee did not influence the results of the measurements. It is possible to follow, stable or changed, characteristics of DN over time.

Electrochemical impedance spectroscopy plays an important role in biosensor science thanks to the possibility of finding specific information from processes with different kinetics at a chosen electrode potential in one experiment. In this paper we briefly discuss label-free impedimetric biosensors described in the literature. A novel method for neutral interpretation of impedance data is presented that includes complex number chemometrics. Three examples are given based on impedance measurements on synthetic biomembranes, in this case a lipid monolayer deposited on a mercury electrode. The interaction of various compounds with the monomolecular lipid layer is illustrated with the following: (1) different concentrations of magainin (Geladi et al. in Proc. Int. Fed. Med. Biomed. Eng. 9:219-220, 2005); (2) different derivatives of gramicidin A (Lindholm-Sethson et al. in Langmuir 24:5029-5032, 2007), and (3) an antimicrobial peptide (Ringstad et al. in Langmuir 24:208-216, 2008).

Clinical studies may be carried out using non-invasively collected near infrared spectra of patient skin. Two problems encountered are: (1) data reduction to go from thousands of wavelengths to some clinically relevant estimator and (2) getting statistical significance from noisy data with sometimes very skewed distributions. The problem of data reduction can usually be solved by principal component analysis to get a few meaningful components. In the space spanned by these components, a direction of discrimination may have to be found, typically discrimination between treated and control. A visual difference in a score plot is often not enough; statistical significance has to be demonstrated. Once a univariate estimator is found, non-parametric testing can show significant differences, even if the data are noisy and have an unknown and skewed distribution. The NOPRAPOD method combines the actions of finding a direction in a reduced data space and performing the non-parametric significance testing by producing a disk of significance. Two examples are included. Example one is from a study of diabetes-related neuropathy where it is shown that significant differences show up in the NIR spectra. Example two is from a study of post-operative radiation treatment of breast cancer patients, where it is shown that radiation effects (erythema) and the effect of lotion can be determined with an indication of significance from the NIR spectra.

A non-blinded three armed study of the effect of Aloe vera, Essex and no lotion on erythema was performed. The erythema is an effect of radiotherapy treatment in breast cancer patients. The study required testing of objective methods for measuring the erythema. The chosen experimental methods were Near Infrared Spectroscopy, Laser Doppler Imaging and Digital Colour Photography. The experimental setup was made in such a way that in parallel with testing the effect of the lotions there was also a test of the sensitivity of the instruments. Fifty women were selected consecutively to participate in the study. They were all subjected to treatment with high-energy electrons (9-20 MeV) after mastectomy, 2Gy/day to a total dose of 50 Gy. Measurements were performed before the start of radiotherapy and thereafter once a week during the course of treatment. Aloe vera and Essex lotion were applied twice every radiation day in selected sites. The increase in skin redness could be monitored with all techniques with a detection limit of 8 Gy for Digital Colour Photography and Near Infrared Spectroscopy and 18 Gy for Laser Doppler Imaging. In clinical practice our recommendation is to use Digital Colour Photography. No significant median differences were observed between the pairs no lotion-Essex, no lotion-Aloe vera and Essex-Aloe vera for any of the techniques tested.

The present thesis proposes new methods for obtaining objective and accurate diagnoses in modern healthcare. Non-invasive techniques have been used to examine or diagnose three different medical conditions, namely neuropathy among diabetics, radiotherapy induced erythema (skin redness) among breast cancer patients and diagnoses of cutaneous malignant melanoma. The techniques used were Near-InfraRed spectroscopy (NIR), Multi Frequency Bio Impedance Analysis of whole body (MFBIA-body), Laser Doppler Imaging (LDI) and Digital Colour Photography (DCP).

The neuropathy for diabetics was studied in papers I and II. The first study was performed on diabetics and control subjects of both genders. A separation was seen between males and females and therefore the data had to be divided in order to obtain good models. NIR spectroscopy was shown to be a viable technique for measuring neuropathy once the division according to gender was made. The second study on diabetics, where MFBIA-body was added to the analysis, was performed on males exclusively. Principal component analysis showed that healthy reference subjects tend to separate from diabetics. Also, diabetics with severe neuropathy separate from persons less affected.

The preliminary study presented in paper III was performed on breast cancer patients in order to investigate if NIR, LDI and DCP were able to detect radiotherapy induced erythema. The promising results in the preliminary study motivated a new and larger study. This study, presented in papers IV and V, intended to investigate the measurement techniques further but also to examine the effect that two different skin lotions, Essex and Aloe vera have on the development of erythema. The Wilcoxon signed rank sum test showed that DCP and NIR could detect erythema, which is developed during one week of radiation treatment. LDI was able to detect erythema developed during two weeks of treatment. None of the techniques could detect any differences between the two lotions regarding the development of erythema.

The use of NIR to diagnose cutaneous malignant melanoma is presented as unpublished results in this thesis. This study gave promising but inconclusive results. NIR could be of interest for future development of instrumentation for diagnosis of skin cancer.

A group of 34 diabetic men, with different degrees of diabetes complications, including skin changes, were studied by near-infrared (NIR) spectroscopy and total body multi-frequency bio-impedance analyses (MFBIA-body). Skin reflectance spectra were measured with a fibre-optic probe in four locations (sites): hand, arm, leg and foot. As control subjects, a group of 23 healthy males were also measured. A combined multivariate analysis of the two types of spectrum was performed. It was concluded that the NIR method has the potential to detect diabetes-related skin conditions and also that the combination of the two techniques provides a higher potential for classification and discrimination of the skin conditions, with correct classification increasing from 63% to 85%.

A group of 15 diabetic persons with different degrees of diabetes complications, including skin changes, was studied by Fourier Transform Near Infrared (FT-NIR) spectroscopy. Skin reflectance spectra were measured with a fibre-optic probe in four locations (sites): hand, arm, leg and foot. For reference, a group of 28 healthy controls was also measured. Multivariate analysis of the NIR spectra obtained shows a high potential for classification and discrimination of the skin conditions. Valuable indications for future experiments can be observed.