Assessment of advanced glycated end product accumulation in skin using auto fluorescence multispectral imaging
Introduction
Advanced glycation endproducts (AGEs) are long-term indicators of metabolic and glycemic stress that can be found in human skin. They derive from the modifications of proteins or lipids that after contact with aldose sugars become glycated [1]. Factors that affects the formation of AGEs are: extended periods of hyperglycemia; oxidant stress in the cellular environment; and the rate of turnover of proteins for glycoxidation [2].
AGEs can also be absorbed through the diet [3]. Foods high in protein and fat are especially rich in AGEs. In addition, increased cooking temperatures, like broiling and frying, and increased cooking times lead to increased amounts of AGEs [4].
Inside the tissue, AGEs can alter cell structure and function, contribute to diabetes related micro- and macrovascular complications [5], and may modify the extracellular matrix [6]. They may also lead to the release of free radicals [6], block the activity of nitric oxide inside the endothelium [7] and increase the amount of reactive oxygen species [8]. When the AGEs have been formed inside the tissue, their turnover time is very long.
Considering the negative effects of AGEs in tissue, an objective way of quantify such an accumulation is of clinical value. Since several AGEs exhibit characteristic fluorescence, this physical effect can be exploited to perform a non-invasive assessment of accumulation increases into human tissues. Significant correlations have been found between skin autofluorescence (AF) and levels of skin AGEs like pentosidine, as obtained from skin biopsies when studying e.g. diabetes mellitus [9]. Skin AF can be used as a predictor for assessing how diseases with increased cardiovascular risk develops. Koetsier et al. [10] suggest that UV stimulations by a broad excitation range of 355–405 nm, is adequate for inducing AF for diagnostic purposes.
A commercial device, the AGE Reader (Diagnoptics Technologies B.V., Groningen, The Netherlands), has become available to assess skin auto fluorescence for clinical purposes [11]. A black light tube, with a peak wavelength of 370 nm is used to illuminate a small region of the skin on the forearm. An optical fiber detects the emission and reflected excitation light, and a spectrometer is used to measure the intensity spectrum. This device is limited to single-point measurements performed in contact to forearm skin.
The aim of this work is to demonstrate the feasibility of quantifying fluorescent AGE deposits in skin tissue using a two-camera setup with optical band pass filters during ultraviolet (UV) exposure. Such a tool enables the analysis of the spatial distribution of AGE in tissue and can be used in devices devoted to remote monitoring and self-monitoring whenever trends in AGE tissue content are required to be traced over time, such as a smart mirror. Incorporating physiological measurements in a smart mirror will increase its medical value [12]. As a proof-of-concept, the AGE level quantified with the proposed camera setup will be compared to readings from a commercial instrument for single point measurements performed in contact to arm skin tissue.
Section snippets
AGE auto fluorescence and quantification
The possibility for detecting the AGE related auto fluorescence spectrum in an imaging setup was initially evaluated in a pilot study using a HSI (Hyper Spectral Imaging) system consisting of a monochromatic camera (Dolphin F-145B, Allied Vision Technologies GmbH, Germany) with an attached tuneable LCTF (Liquid Chrystal Tuneable Filter; VariSpec VIS 7 nm FWHM, PerkinElmer Inc., US) band-pass filter. This setup was capable of capturing HSI data in the 445–720 nm range. The initial evaluation
Results
When analyzing the correlation between the AGE Reader data and the AGE MSI data, only the 15 subjects that displayed any measures from the AGE Reader were included (one subject with the darkest skin pigmentation was excluded). The four additional recordings having the ambient light turned on were also excluded from the statistical comparisons.
The AGE index was measured using MSI recordings on facial skin (AGEMSI,face) and on forearm skin (AGEMSI,arm). These indices were compared to those from
Discussion
When skin is exposed to UV light in the 350–400 nm range, AGE tissue compounds will start to fluoresce by re-emitting the absorbed photons as light with a longer wavelength. By detecting the auto fluorescence it is possible to track changes in the relative amount of AGE products in skin. However, the auto fluorescence is an extremely weak signal when compared to the amount of elastically scattered photons. Hence it is challenging to accurately detect and quantify this signal. There is a
Conclusions
AGE measured with MSI in forearm skin was significantly correlated (p=0.005) with the AGE reference method (AGE Reader on forearm skin). The relationship to AGE with MSI in facial skin was slightly weaker and borderline significant (p=0.078). This could indicates that the AGE content varies between forearm and facial skin areas. The recordings of AGE level with ambient light turned on showed only a minor influence of ambient light. These results show proof-of-principle for measuring AGE with
Conflicts of interest statement
The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed
Acknowledgments
This work was supported by the European Commission under the Seventh Framework Programme for the Collaborative project under Grant Agreement no. 611516 (SEMEOTICONS).
The authors would like to thank Giuseppe Coppini, Sara Colantonio, Maria Aurora Morales, Paolo Marraccini and the rest of the team from CNR-ISTI and CNR-IFC for making the experimental part possible.
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