Future development of application of IR microspectroscopy for clinical optical diagnosis of skin cancers demands
dedicated software that can perform analysis, enabling clinically relevant information in the measured spectra to be fully
extracted. Presented numerical modeling and analytical treatment of IR spectra of a variety of skin cancers contains an
option to differentiate those from normal skin tissue, recognize patterns, and set information-rich data of clinical and
scientific relevance.
Skin tissue infrared (IR) microspectroscopy may work as an optical diagnostic method for common skin cancer detection,
progression, and specific characterization of carcinogenesis in skin tumours. Spectral results from BCC, SCC and MM
skin samples demonstrated significant levels of the multiplet at about 1055 cm-1. Its activity level strongly correlated with
the activity level of the most prominent peak in DNA/RNA triad in 5 BCC, in 3 SCC and only in 1 MM patient. DNA-RNA
and DNA-DNA interactions as I965 < I1055 < Imax level DNA/RNA triad peak were the most clearly observed in 3 BCC
patients with high-leveled peaks of nucleic acids, that were presented as I965 < I1055 > Imax level DNA/RNA triad peak in 3 SCC patients with the highest activity levels. Although mean values and the intensities of nucleic acids in the patients
with MM showed strong correlation between each other, independent on the level of their activity, interactions differed
individually. DNA-protein interactions were mostly expressed between intensities of DNA/RNA triad peaks and
non-descriptive proteins, that were in agreement between BCC and SCC, but not in MM. Protein-protein interactions were
similar among the patients, generally indicating the grade of activity in cells in tissues.
Method of the lag/latency time (LT) measurement, calculation and interpretation can be simultaneously applied to study in vivo
glucose diffusion from the capillary to the skin tissue, to calibrate spectroscopically measured glucose levels during real-time
glucose monitoring of dynamic processes in the skin tissue and to study glucose optical properties in the living skin tissue.
Based on previous reports on determining interstitial glucose levels and their LT's by HATR-FTIR spectroscopy, here the LT
was calculated for each glucose absorbance level at about 1030-41, 1080, 1118 and 1153 cm-1 during oral glucose tolerance test
(OGTT) with different doses (5g, 20g, 75g). The LT showed dose-dependency and described intra-/inter-subject changes of
skin glucose dynamics in healthy and diabetes subjects. The time required for glucose to diffuse from the capillary to the skin
tissue was shorter in a diabetes subject, than in a healthy subject, independently on intaken dose of glucose. Nevertheless, in
both subjects the LT changes ranged within 050 minutes. Measurement of the LT demonstrated a potential to provide insight
to healthy and diabetic glucose dynamics between the blood and interstitial fluid compartments in the upper layer of the skin
tissue. Also, the LT might be regarded as a method to calibrate dynamic measurements of glucose in vivo by this spectroscopy
method and to characterize living skin tissue glucose optical properties.
Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in
the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for
understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in
vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial
glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the
skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related
1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their
changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and
blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to
the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though
interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise
measurements of interstitial glucose levels may be more important clinically.
Benefits of employing laser and optical technologies in clinical dermatology are enormous, including solving the
complex of questions in diagnosis and treatments of many skin diseases; introducing new methods of diagnosis,
treatment and its evaluation; advancing fundamental understanding not only of physiology of skin itself, but also of pathophysiology of different dermatological diseases and conditions. Through numerous innovations in laser and optical
technologies a variety of specific and important information has become available in clinical dermatology on real-time
normal and lesional skin characterization and visualization, on different type and pattern recognition, on monitoring of
several dermatological conditions, on assessment of various parameters for measuring dynamics of skin lesions with
further possibilities to assess severity of skin symptoms, and on evaluation of different treatment regimes and their
comparisons. After a decade of experiences in inter- and multi-disciplinary research I would like to share the wisdom and
pitfalls of my work how to get laser and optical technologies into clinical practice of dermatological interest, that are
discussed in the paper.
The local microcirculatory dynamics underlying phenomenon of urticarial dermographism (UD) are not yet sufficiently
elucidated in dermatological patients. A fiber optic laser Doppler flowmeter (LDF) was used to monitor skin blood flow
(SBF) changes on the back of the patients with UD before and after application of the series of pressure stimuli (9.8×104, 14.7×104, 19.6×104 and 24.5×104 Pa). All patients acted as self-controls to assess their disease activity by means of SBF values based on response to pressure stimuli before and after treatment with antihistamines, when compared to baseline SBF. Throughout 30 minutes evaluation inter-subject SBF values at pressure-tested sites were noticeably distinguished as high, moderate and low. By LDF we could differentiate the highest development of vascular dynamics after 5 minutes, coming back to normal within about 30 minutes in one group of patients, and the vascular dynamics reaching its maximum in 15 minutes, but with no fade after 30 minutes, in another group of patients. All treatment regimens in both groups of patients by LDF produced a measurable reduction already during 1-2 days of therapy, accompanied by a reduction in SBF baseline values in patients with severe and moderate symptoms of UD.
Reflectance spectrophotometry (RS), laser Doppler flowmetry (LDF) and transepidermal water loss (TEWL) techniques were simultaneously used to non-invasively monitor skin colour (SC), skin blood flow (SBF) and barrier function damage (BFD) in routinely patch-tested Japanese patients in dermatology clinic. The analytical quality, reliability and reproducibility of each technique were compared and analyzed in correlated to visual scoring patch test (PT) reactions as
negative (-), doubtful (+?), weak (+) and strong (++/+++) at 48- and 72-hour monitoring. An attempt was made to quantify predominant in the clinic "+?"- and "+'"-PT-reactions. The relationship between 48 h and 72 h measurements in different reaction groups was poor for TEWL, LDF showed a tendency to decrease at 72 h, but good for RS. A correlation between visual scorings and instrumental mean values was poor for TEWL, good for LDF and excellent for RS. So, measurements by RS were the most statistically significant to non-invasively monitor and quantify doubtful, weak and strong PT reactions, accordingly providing continuous data grading of reaction intensity suitable in the clinic. Moreover, monitoring of SC changes was the most reliable parameter for the quantitative distinguishing of doubtful and weak reactions in pigmented skin.
Attempts were made to non-invasively detect glucose-specific spectral signals in the skin by ATR-FTIR spectroscopy. In
vivo spectra were collected from the inner wrists of healthy, prediabetes and diabetes subjects in the 750-4000 cm-1
region, with a closer assessment of the glucose-related region between 1000 and 1180 cm-1. Spectra in vivo showed
glucose-specific peaks at 1030, 1080, 1118 and 1151 cm-1, as a variety of glucose solutions are found in vitro. Based on
the differences of intensities at 1030 and 1118 cm-1 two spectral patterns were seen: I1118 > I1030 for a diabetes and I1030>
I1118 for non-diabetes subjects. The peak at 1030 cm-1 was used to assess glucose concentrations in the skin due to its
good correlation with glucose concentrations in vitro. Calculated mean values of the peak at 1030 cm-1 showed evidence
of correlation with blood glucose levels when grouped as ≤ 140, 140-200 and ≥ 200 mg/dL, though there was no constant
correlation between them when compared before/after OGTT or at the fasting/postprandial states. Absorbances at 1030
cm-1 were not only increased in a dose-dependent manner in a diabetes patient, but were also generally higher than in
non-diabetes subjects at 30 min OGTT assessment. Also we could monitor absorbances at 1030 cm-1 and determine their
changes in the skin tissue at different times of OGTT. We assume that our approach to in vivo measurement and
monitoring of glucose concentrations at 1030 cm-1 may be one of the indicators to assess glucose activity level and its
changes in the skin tissue, and has further implications in the study of clinical and pathophysiological aspects of
hyperglycemia in diabetes and non-diabetes subjects by ATR-FTIR spectroscopy.
A few recent applications of lasers and optical technologies in clinical dermatology have already shown its potential not
only to be objective, accurate, rapid, reproducible, non-invasive, non-destructive methods, but also able to study
pathophysiology and biophysics of the skin, qualitatively and quantitatively perform evaluation and monitoring of the
dynamics of skin lesions in vitro, ex vivo and especially in vivo, that have not been described before in any textbook of
dermatology. Here are demonstrated some data from clinical dermatological studies by using laser Doppler flowmetry,
reflectance spectrophotometry, infrared microspectroscopy and fiberoptic near-infrared Raman spectroscopy for
investigating pathophysiological and pharmacological aspects of some dermatological diseases, as well technical
availability and reliability of utilized techniques for selected purposes in the clinic. Such a survey of a number of
applications by a variety of laser and optical technologies aims to receive much more attention by a dermatological
community to further introduce new potential applications by using this kind of technologies in the clinical settings, and
also to expand interdisciplinary knowledge considering presently determined advantages and disadvantages of the
probed instrumentation in the hospital.
Currently, measuring Raman spectra of tissues of living patients online and in real time, collecting the spectra in a very short measurement time, and allowing diagnosis immediately after the spectrum is recorded from any body region, are specific advantages that fiber optic near-infrared Raman spectroscopy (NIR RS) might represent for in vivo clinical applications in dermatology. We discuss various methodological aspects and state of the art of fiber optic NIR RS in clinical and experimental dermatology to outline its present advantages and disadvantages for measuring skin in vivo, particularly its water content. Fiber optic NIR Fourier transform (FT) RS has been introduced to dermatological diagnostics to obtain information regarding the molecular composition of the skin up to several hundred micrometers below the skin surface in a relatively fast nondestructive manner. This has been especially important for probing for in vivo assessment of cutaneous (intradermal) edema in patients patch test reactions. Fiber optic NIR FT Raman spectrometers still require further technological developments and optimization, extremely accurate water concentration determination and its intensity calculation in skin tissue, and for clinical applications, a reduction of measurement time and their size. Another promising option could be the possibility of applying mobile and compact fiber optic charge-coupled device (CCD)-based equipment in clinical dermatology.
Tissue infrared microscopy has been applied in dermatopatholoical assessment of common benign, premalignant, and malignant skin lesions in order to observe processes from benign to malignant transformation and compare them to normal. Various approaches how to develop computerised data processing and to sort out useful information within grouped lesion categories against huge inter- and intra-sample variability included spectral and multivariate data treatment. Spectral data processing was carried out to assign spectral bands in the measured spectra using the classical group frequency approach. A multivariate technique, principal component analysis (PCA), was performed to identify and to confirm the wavenumber values that contributed to most of the variance within 1661 points of the spectrum, to evaluate and maximise the differences in the spectra by reducing the number of variables characterising each patient, pathology category and skin component (epidermis, dermis, the lesion and its adjacent area). The results suggest that there is a common tendancy for the observed spectral features in benign, premalignant and malignant lesions directly related to protein conformations and nucleic acid bases in the 800-1750 cm-1 region, that was possible to distinguish from normal against a huge background of inter- and intra-sample variability.
The aim of the present study is to examine the availability of NIR FT Raman spectroscopy in the clinical evaluation of positive allergic and irritant or doubtful patch test reactions. Instrumental measurements at 42 positive patch test sites in 16 patients were compared visually and evaluated at 48 h and 72 h in order to examine the sensitivity of this method to detect the biochemical changes occurring at the sites of the patches. Raman spectra of normal control skin and skin reacting to patches on the back were obtained with an FRA 106 Raman module on a Bruker IFS 66 optics system (Bruker, Karlsruhe, Germany). The most significant changes in the spectra were detected in the region specific for water content and protein structure in both types of reactions at 48 h and 72 h, compared to normal skin.
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