In vivo method for evaluating sunscreen protection against high-energy visible light.

BACKGROUND: Overexposure to sunlight can have many harmful biological effects on the skin, leading to skin cancer and photoaging. As ultraviolet (UV) radiation has been identified as a cause of DNA damage and oxidative stress in the skin, the photoprotection provided by sunscreens is evaluated through their ability to filter UV light, using the sun protection factor (SPF). However, recent data have shown that high-energy visible (HEV) light can also cause biological skin damage. OBJECTIVES: To develop a new in vivo method for evaluating the protection provided by sunscreens across a broad range of wavelengths, including the HEV band, based on multispectral image analysis. METHODS: This study evaluated the absorption properties of six commercially available sunscreens (five SPF 50+ products containing organic UV filters, and one product containing the wide spectrum filter, phenylene bis-diphenyltriazine [TriAsorB™]) and of a control product containing no filter. Multispectral images were acquired from the skin on the forearms of healthy volunteers, before and after application of the test products. Images taken with LEDs emitting light at wavelengths ranging from UV to infrared were used to generate light reflectance maps for each product. The levels of absorbance of light in the UV and visible bands were then calculated. RESULTS: The product containing the wide spectrum filter exhibited significantly higher absorbance over the HEV band (380-450 nm) than the control product and the other commercial sunscreens. All the sunscreens tested showed the same level of absorbance at 365 nm (UVA). CONCLUSIONS: Multispectral imaging provides a simple and reliable in vivo method for assessing the real-world protection provided by sunscreens against all forms of photo-induced skin damage, including that induced by HEV radiation.

Protection against summer solar lentigo over-pigmentation with a SPF30 daily cream.

BACKGROUND/PURPOSE: The aim of this study was to measure lentigines' pigmentation over a long period of time and evaluate if summer over-pigmentation can be avoided by the use a SPF30 day skin cream. METHODS: Seventeen healthy female volunteers aged 50 and over and presenting lentigines participated in the study from spring to summer. Throughout the study, all subjects applied a SPF30 daily skin cream to only one hand. Color measurements of the target lesions were performed with a chromameter and with a color-calibrated camera. Target lesions were also imaged with in vivo reflectance confocal microscopy (RCM). A specific procedure for re-registering the images was developed to ensure that the same papillae were measured over time. RESULTS: Both color measurement methods, chromametry and color-calibrated camera, showed that lentigines treated over time with the SPF30 day skin cream were significantly lighter than the non-treated lentigines. The RCM images showed a decrease in the papillary contrast for the treated lentigines. CONCLUSION: This study shows that this over-pigmentation can be avoided using a SPF30 day skin cream. Moreover, we have demonstrated that very fine re-registration of the RCM images is possible and ensures a more robust analysis.

Optical coherence tomography: An efficient imaging method for the visualization of human epidermis orientation.

Recently, it has been shown that epidermal sheets taken from suction blisters are very appropriate skin samples for Multi-Photon (MP) microscopy. However, we observed that image quality was much better when the sample was visualized through the basale side. Thus, the epidermis orientation needs to be controlled before MP imaging. We observed that the use of standard laboratory binoculars led to a high rate of false results. In this context, we showed that optical coherence tomography provided clear images of the epidermis orientation without loss of sample integrity and thus represents an effective technique before slide sealing and MP analysis.

Follow-up of solar lentigo depigmentation with a retinaldehyde-based cream by clinical evaluation and calibrated colour imaging.

BACKGROUND AND OBJECTIVE: To assess an objective method evaluating the effects of a retinaldehyde-based cream (RA-cream) on solar lentigines; 29 women randomly applied RA-cream on lentigines of one hand and a control cream on the other, once daily for 3 months. METHODS: A specific method enabling a reliable visualisation of the lesions was proposed, using high-magnification colour-calibrated camera imaging. Assessment was performed using clinical evaluation by Physician Global Assessment score and image analysis. Luminance determination on the numeric images was performed either on the basis of 5 independent expert's consensus borders or probability map analysis via an algorithm automatically detecting the pigmented area. RESULTS: Both image analysis methods showed a similar lightening of ΔL* = 2 after a 3-month treatment by RA-cream, in agreement with single-blind clinical evaluation. CONCLUSION: High-magnification colour-calibrated camera imaging combined with probability map analysis is a fast and precise method to follow lentigo depigmentation.

Dual-parameter optimisation of the elastic properties of skin.

This paper presents a procedure for characterising the mechanical properties of skin using stochastic inverse identification. It is based on the minimisation of a cost function relative to the comparison between experimental suction experiments and their corresponding finite element models. Two different models are compared: a classical single-layer approach and a dual-layer medium which account for both the dermis and the hypodermis. Finite element results are used to construct the pre-optimisation database which is required for the inverse analysis. To compare the calculations, the entire identification is based on a dual-parameter optimisation procedure: for the single-layer approach a quadratic hyperelastic constitutive equation is used, whereas for the dual-layer medium a simple neo-Hookean potential is used. Theoretical conclusions, which are developed first, are then compared with actual case studies.

Automatic measurement of epidermal thickness from optical coherence tomography images using a new algorithm.

BACKGROUND/PURPOSE: Optical coherence tomography (OCT) is an imaging system that enables in vivo epidermal thickness (ET) measurement. In order to use OCT in large-scale clinical studies, automatic algorithm detection of the dermo-epidermal junction (DEJ) is needed. This may be difficult due to image noise from optical speckle, which requires specific image treatment procedures to reduce this. In the present work, a description of the position of the DEJ is given, and an algorithm for boundary detection is presented. METHODS: Twenty-nine images were taken from the skin of normal healthy subjects, from five different body sites. Seven expert assessors were asked to trace the DEJ for ET measurement on each of the images. The variability between experts was compared with a new image processing method. RESULTS: Between-expert variability was relatively low with a mean standard deviation of 3.4 µm. However, local positioning of the DEJ between experts was often different. The described algorithm performed adequately on all images. ET was automatically measured with a precision of < 5 µm compared with the experts on all sites studied except that of the back. Moreover, the local algorithm positioning was verified. CONCLUSION: The new image processing method for measuring ET from OCT images significantly reduces calculation time for this parameter, and avoids user intervention. The main advantages of this are that data can be analyzed more rapidly and reproducibly in clinical trials.

Assessment of embryonic growth in chicken eggs by means of visible transmission spectroscopy.

During this work, it was investigated whether spectral measurements can be used to monitor embryonic growth. An experiment was conducted in which both the transmission spectra and embryonic weight were determined on 240 eggs (Cobb, 37 weeks) between Day 5 and Day 10 of incubation. The spectral data were linked to embryonic weight by means of a partial least squares analysis. Different preprocessing procedures were compared during this work, that is, smoothing, multiplicative scatter correction (MSC), and first- and second-order derivative. Compared to the remainder of the preprocessing procedures, MSC leads to a considerable improvement of the prediction capability of the embryonic weight. The ratio of performance to deviation obtained for the MSC spectra equaled 4.5 indicating that a very accurate prediction of embryonic weight is feasible based on the VIS/NIR transmission measurements. Important regions for the prediction are situated around 685-740 nm. It is suggested that the spectral changes in these spectral regions result from the displacement of carotenoids from the yolk into the blood circuitry.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

BACKGROUND: Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. OBJECTIVES: The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. METHODS: High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. RESULTS: led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. CONCLUSIONS: High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

A multitechnique evaluation of topical corticosteroid treatment.

BACKGROUND/PURPOSE: Corticosteroids are widely prescribed for systemic or local treatment of inflammatory autoimmune disorders. Long-term therapy is associated with side effects and causes cutaneous atrophy of the epidermis and the dermis. The present study aims to evaluate with several noninvasive techniques, the skin modifications observed during corticosteroids treatment. The potential of skin mechanical measurement and ultrasound radio frequency (RF) signal analysis are proposed as new measures more closely related to the functional impairments. METHODS: Thirteen young healthy women volunteers had two applications per day on one arm of topical Clobetasol propionate 0.05% for 28 days, and they were followed for 28 days more. Skin modifications were studied by high-frequency ultrasound imaging, ultrasound RF signal analysis, optical coherence tomography and by the suction test. RESULTS: For all the techniques, a statistically significant change is observed with treatment. Large variations, around 30%, are observed for all techniques, but less for ultrasound imaging (10%). Dermis and epidermis thickness presented stable measurements on the nontreated zone. At the end of the study, measures returned to normal. The dynamic is mainly observed within the first 14 days of treatment and within the first 14 days after its cessation. CONCLUSION: Similar dynamics of skin modification during corticosteroid treatment was observed with very different techniques. Moreover, the potential of RF ultrasound analysis and mechanical skin measurement for characterizing skin structural and functional impairments has been evaluated.

Quantitative magnetic resonance imaging of subcutaneous adipose tissue.

BACKGROUND/PURPOSE: Quantitative transverse relaxation time (T(2)) magnetic resonance (MR) imaging has been used with the aim to characterize subcutaneous adipose tissue. Protons in adipose tissue have a fast exchange behavior giving bi-component transverse relaxation processes with short and long relaxation time values depending on the tissue properties. METHODS: MR images were acquired on a 1 T Siemens MR scan using a multi-spin-echo sequence. A high sensitive surface coil, enabling low noise MR images with voxel size of 10 mm(3), was used for performing accurate quantitative T(2) imaging. These acquisition parameters were determined by a preliminary study performed on an oil phantom known to be a valuable model for mimicking in vivo adipose tissue. In vivo study of the thigh adipose tissue was carried out on 30 volunteers. 20 women with various clinically diagnosed cellulite grades and 10 males, among them five showed overweight. Tissue characterization was finally performed through the analysis of the T(2) distributions. RESULTS: Phantom study showed that improvements in the precision in T(2) measurement are obtained at the expense of the spatial resolution. Uncertainties in T(2) measurements are three times lower by considering a region of interest of 3 x 3 pixels compared with a pixel by pixel analysis. The in vivo study showed that women groups present higher mean short T(2S) component values than men. Histogram of T(2) distribution showed that the maximum amplitude is observed at a lower value for the overweight men group. In addition, larger values around the septae were visualized on the long relaxation time images. CONCLUSIONS: This study shows that precise T(2) map of adipose tissue can be computed. The balance between precision and spatial resolution is examined. Preliminary results relative to tissue organization and to difference between clinical groups proves the potential of the quantitative MRI.

A nonlinear elastic behavior to identify the mechanical parameters of human skin in vivo.

BACKGROUND/PURPOSE: Various analyses have been performed to identify the mechanical properties of the human skin tissue in vivo. They generally use different approaches and hypotheses (behavior laws as well as mechanical tests) and the obtained results are consequently difficult to analyze and compare. In this paper, an inverse method that can be adapted to any kind of mechanical tests and behavior laws is presented. METHOD: A suction deformation performed on the volar aspect of the forearm of a subject is considered. This test is modeled with the finite element method to compare the experimental and simulated curves using an inverse method that allows the skin mechanical parameters identification. This process is based on two optimization algorithms, Kalman's filter and Gauss-Newton's methods. To account for the nonlinear behavior of the skin, a specific nonlinear elastic law, which is then compared with standard linear elastic and neo-Hookean's mechanical behaviors, was developed. RESULTS: The obtained results first prove that neither linear elasticity nor neo-Hookean's laws can be used to model the skin. On the contrary, the nonlinear elastic model presents a relevant fit of the experimental curves. The skin thickness is also proved to be another key point to be taken into consideration. CONCLUSIONS: The obtained results are successfully compared with literature and the reliability of the proposed method is underlined with the identification of 300 additional experimental curves. The different works we are currently focusing on are finally introduced.

In vivo visualization of hyaluronic acid injection by high spatial resolution T2 parametric magnetic resonance images.

BACKGROUND/PURPOSE: In recent years, increasing use of injectable resorbable fillings has been reported for facial wrinkle treatment. However, the physiological processes involved such as the localization and subsequent diffusion of the injected product in skin tissues are poorly documented. This may be noninvasively achieved using quantitative magnetic resonance imaging (MRI), which is duly presented in this pilot study. METHODS: Hyaluronic acid (HA) was injected intradermally in the forearm of a young male volunteer. High-resolution MRI scans using a surface antenna were performed just after injection, and after 2, 4 and 9 months. Morphological images were compared with transverse relaxation time (T(2)) images computed from a pixel-by-pixel analysis. RESULTS: On high-resolution morphological MR images the HA injection is barely visible, but with quantitative MRI the zone of injection is clearly seen. This is due to HA having a distinctly different transverse relaxation time, T(2) approximately 600 ms, compared with dermal and hypodermal tissues, 35 and 80 ms, respectively. CONCLUSION: These preliminary results demonstrate the ability of the T(2) images for in vivo visualization of the filler agent and also for characterization of tissue modifications. In addition, the diffusion and progressive degradation of the filler agent can be monitored by T(2) measurements over time.

High spatial resolution quantitative MR images: an experimental study of dedicated surface coils.

Measuring spin-spin relaxation times (T2) by quantitative MR imaging represents a potentially efficient tool to evaluate the physicochemical properties of various media. However, noise in MR images is responsible for uncertainties in the determination of T2 relaxation times, which limits the accuracy of parametric tissue analysis. The required signal-to-noise ratio (SNR) depends on the T2 relaxation behaviour specific to each tissue. Thus, we have previously shown that keeping the uncertainty in T2 measurements within a limit of 10% implies that SNR values be greater than 100 and 300 for mono- and biexponential T2 relaxation behaviours, respectively. Noise reduction can be obtained either by increasing the voxel size (i.e., at the expense of spatial resolution) or by using high sensitivity dedicated surface coils (which allows us to increase SNR without deteriorating spatial resolution in an excessive manner). However, surface coil sensitivity is heterogeneous, i.e., it--and hence SNR--decreases with increasing depth, and the more so as the coil radius is smaller. The use of surface coils is therefore limited to the analysis of superficial structure such as the hypodermic tissue analysed here. The aim of this work was to determine the maximum limits of spatial resolution and depth compatible with reliable in vivo T2 quantitative MR images using dedicated surface coils available on various clinical MR scanners. The average thickness of adipose tissue is around 15 mm, and the results obtained have shown that obtaining reliable biexponential relaxation analysis requires a minimum achievable voxel size of 13 mm3 for a conventional volume birdcage coil and only of 1.7 mm3 for the smallest available surface coil (23 mm in diameter). Further improvement in spatial resolution allowing us to detect low details in MR images without deteriorating parametric T2 images can be obtained by image filtering. By using the non-linear selective blurring filter described in a previous work, the voxel size was reduced to 0.8 mm3, allowing us to detect microstructures such as fibrous septae while preserving precision in T2 measurements. This paper provides practical information allowing us to perform reliable T2 quantitative MR micro images. High resolution imaging with dedicated surface coils, which is only well-suited to near surface organs, might lead to highly valuable results in this context, especially to analyse the hypodermis involved in the lipodystrophy seen in patients with human immuno-deficiency virus (HIV).

A post-processing method for multiexponential spin-spin relaxation analysis of MRI signals.

Quantitative MR imaging is a potential tool for tissue characterization; in particular, proton density and proton relaxation times can be derived from MR signal analysis. However, MR image noise affects the accuracy of measurements and the number of tissue parameters that can be reliably estimated. Filtering can be used to limit image noise; however this reduces spatial resolution. In this work we studied, using both simulations and experiments, a filter called a 'selective blurring filter'. Compared to other classical filters, this filter achieves the best compromise between spatial resolution and noise reduction. The filter was specifically used to reliably determine the bi-component transverse relaxation of protons in adipose tissue. Long and short relaxation times and the relative proton fraction of each component were obtained with a degree of uncertainty of less than 10% and an accuracy of 95%.

Interindividual variability in the hemispheric organization for speech.

A PET activation study was designed to investigate hemispheric specialization during speech comprehension and production in right- and left-handed subjects. Normalized regional cerebral blood flow (NrCBF) was repeatedly monitored while subjects either listened to factual stories (Story) or covertly generated verbs semantically related to heard nouns (Gener), using silent resting (Rest) as a common control condition. NrCBF variations in each task, as compared to Rest, as well as functional asymmetry indices (FAI = right minus left NrCBF variations), were computed in anatomical regions of interest (AROIs) defined on the single-subject MNI template. FAIs were predominantly leftward in all regions during both tasks, although larger FAIs were observed during Gener. Subjects were declared "typical" for language hemispheric specialization based on the presence of significant leftward asymmetries (FAI < 0) in the pars triangularis and opercularis of the inferior frontal gyrus during Gener, and in the middle and inferior temporal AROIs during Story. Six subjects (including five LH) showed an atypical language representation. Among them, one presented a right hemisphere specialization during both tasks, another a shift in hemispheric specialization from production to comprehension (left during Gener, right during Story). The group of 14 typical subjects showed significant positive correlation between homologous left and right AROIs NrCBF variations in temporal areas during Story, and in temporal and inferior frontal areas during Gener, almost all regions presenting a leftward FAI. Such correlations were also present in deactivated areas with strong leftward asymmetry (supramarginalis gyrus, inferior parietal region). These results suggest that entry into a language task translates into a hemispheric reconfiguration of lateral cortical areas with global NrCBF increase in the dominant hemisphere and decrease in the minor hemisphere. This can be considered as the setting up of a "language mode", under the control of a mechanism that operates at a perisylvian level. On top of this global organization, regional variations carry on the performance of the cognitive operations specific to the language task to be performed. Hemispheric relationships could be different in atypical subjects, with either between task hemispheric regulation differences or differences in regional specialization.

Vibration analysis on incubating eggs and its relation to embryonic development.

Coucke (1998) was the first to use acoustic resonance analysis to monitor embryo development in chicken eggs. He remarked that at around 100 hours of incubation, the course of the resonant frequency and damping changed abruptly in the case of fertile eggs. He also showed that these changes were related to a physiologic event during early embryonic development. The objective of our study is to monitor the course of the vibration parameters during the early incubation of chicken eggs and to relate these changes to egg and embryo characteristics. A total of 72 Hybro eggs were incubated vertically in a small incubator at standard conditions. Several egg parameters were measured before incubation. During the early stages of incubation the vibration behavior of these eggs was monitored. The time at which the damping of the vibration suddenly changed, the diameter of the eggs and their interaction were found to be significant explanatory variables in order to predict hatching time. A correlation coefficient r of 0.72 was obtained.