Non-Invasive Determination of Breslow Index

Breslow index is defined as maximal thickness of cutaneous malignant melanoma measured in several slides from the top of the granular cell layer to the deepest point of invasion. Prognosis, prediction of sentinel lymph node status as well as excision margins are based on Breslow index determination. Non-invasive Breslow index determination would allow one-time procedure for melanoma clinical management which would be of utmost medical interest for several reasons: unimpaired sentinel lymph node status, low morbidity, pain and stress associated to surgical excision margins. However, as explained throughout the current chapter, such a determination requires melanoma diagnosis prior to Breslow determination. As a result, all techniques reported in this chapter (based on ultrasounds, optical waves or both), not only demonstrate their ability to determine Breslow thickness but also their ability to increase diagnosis accuracy. Ultrasonography and dermoscopy are currently evaluated in clinical environments. Diffuse reflectance spectroscopy, has been tested on tissue phantoms. Infrared microimaging and photoacoustic microscopy have shown preliminary results on fixed and paraffin-embedded tissues without staining and on xenografted tumours on mice respectively. Finally, optical coherence tomography and confocal microscopy may have a clinical interest in the management of very thin melanomas but require further studies to show their potential interest

Source separation approach for the analysis of spatially resolved multiply excited autofluorescence spectra during optical clearing of ex vivo skin

Spatially resolved multiply excited autofluorescence spectroscopy is a valuable optical biopsy technique to investigate skin UV-visible optical properties in vivo in clinics. However, it provides bulk fluorescence signals from which the individual endogenous fluorophore contributions need to be disentangled. Skin optical clearing allows for increasing tissue transparency, thus providing access to more accurate in-depth information. The aim of the present contribution was to study the time changes in skin spatially resolved and multiply excited autofluorescence spectra during skin optical clearing. The latter spectra were acquired on an ex vivo human skin strip lying on a fluorescent gel substrate during 37 minutes of the optical clearing process of a topically applied sucrose-based solution. A Non Negative Matrix Factorization-based blind source separation approach was proposed to unmix skin tissue intrinsic fluorophore contributions and to analyze the time evolution of this mixing throughout the optical clearing process. This spectral unmixing exploited the multidimensionality of the acquired data, i.e., spectra resolved in five excitation wavelengths, four source-to-detector separations, and eight measurement times. Best fitting results between experimental and estimated spectra were obtained for optimal numbers of 3 and 4 sources. These estimated spectral sources exhibited common identifiable shapes of fluorescence emission spectra related to the fluorescent gel substrate and to known skin intrinsic fluorophores matching namely dermis collagen/elastin and epidermis flavins. The time analysis of the fluorophore contributions allowed us to highlight how the clearing process towards the deepest skin layers impacts skin autofluorescence through time, namely with a strongest contribution to the bulk autofluorescence signal of dermis collagen (respectively epidermis flavins) fluorescence at shortest (respectively longest) excitation wavelengths and longest (respectively shortest) source-to-detector separations

Proton MR spectroscopy and diffusion MR imaging monitoring to predict tumor response to interstitial photodynamic therapy for glioblastoma

International audienceDespite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated

Caractérisation de la transformation néoplasique de la peau par spectroscopies optiques sur fantôme de mélanome et carcinome épidermoïde murin photo-induit

Autofluorescence and diffuse reflectance spectroscopies were studied as non-invasive tools to discriminate different stages of skin neoplastic transformation and thus to help diagnose the two most lethal skin lesions: cutaneous melanoma and squamous cell carcinoma. Concerning melanoma, skin phantoms were made to simulate several melanoma thicknesses (Breslow index). Spatially-resolved diffuse reflectance spectroscopy (using five collection optical fibers set at five different distances from the excitation optical fiber) allowed discrimination (p<0.05) of melanoma layers, the thickness of which was 1 mm different. Since diffuse reflectance spectroscopy has already shown good results in assessing malignancy of pigmented skin lesions, such a spectroscopy could be used as a complementary tool of cutaneous melanoma diagnosis. Using ultra-violet induced squamous cell carcinoma of mouse skin, bimodal spectra (multi-excitation fluorescence and diffuse reflectance) were acquired throughout the 7 month-carcinogenesis. Histological sampling followed spectral acquisition and three histological classes were determined by histo-pathological examination: compensatory hyperplasia, atypical hyperplasia and dysplasia. A fourth “healthy” class consisted in the skin sampled on mice that were never irradiated (control group). Multivariate statistical analysis of the spectral data set showed that combining autofluorescence (best results obtained with a 410 nm excitation) and diffuse reflectance resulted in a 9 percentage point-increase of specificity when discriminating the three types of hyperplasia from one another compared to each modality used alone. Such results need to be confirmed through clinical trials on human patients.L'objectif de ce travail de recherche est d'évaluer la capacité des spectroscopies optiques d'autofluorescence et de réflectance diffuse à caractériser les différents stades de la transformation néoplasique de la peau et ainsi d'aider au diagnostic des deux lésions de peau les plus létales : le mélanome malin et le carcinome épidermoïde. Dans l'étude portant sur le mélanome, un objet-test (« fantôme ») a été développé pour modéliser différentes épaisseurs de mélanome (indice de Breslow). La spectroscopie de réflectance diffuse résolue spatialement (grâce à l'utilisation de cinq fibres optiques réceptrices situées à cinq distances différentes de la fibre optique excitatrice) a montré sa capacité à discriminer (p<0,05) des indices de Breslow simulés grâce à des fantômes d'épaisseur variant par pas d'1 mm. D'autre part, des mesures de spectroscopie bimodale (combinant autofluorescence en multi-excitation et réflectance diffuse) ont été réalisées sur peau murine tout au long des sept mois de photocarcinogenèse. Des prélèvements cutanés ont permis d'établir trois classes histologiques (en plus de la classe saine du groupe contrôle) : hyperplasie compensatoire, hyperplasie atypique et dysplasie. Puis la précision diagnostique a été évaluée par analyse statistique multivariée. Nos principaux résultats montrent que la bimodalité associant autofluorescence (excitation à 410 nm) et réflectance diffuse permet une amélioration de la spécificité de 9 points de pourcentage comparées aux performances de chacune des modalités utilisée seule lors de la discrimination des trois types d'hyperplasie. Des études cliniques doivent maintenant confirmer l'intérêt de ces résultats

Spectroscopic characterisation of skin neoplastic transformation using melanoma phantoms and ultraviolet-induced squamous cell mouse carcinoma

L’objectif de ce travail de recherche est d’évaluer la capacité des spectroscopies optiques d’autofluorescence et de réflectance diffuse à caractériser les différents stades de la transformation néoplasique de la peau et ainsi d’aider au diagnostic des deux lésions de peau les plus létales : le mélanome malin et le carcinome épidermoïde. Dans l’étude portant sur le mélanome, un objet-test (« fantôme ») a été développé pour modéliser différentes épaisseurs de mélanome (indice de Breslow). La spectroscopie de réflectance diffuse résolue spatialement (grâce à l’utilisation de cinq fibres optiques réceptrices situées à cinq distances différentes de la fibre optique excitatrice) a montré sa capacité à discriminer (p<0,05) des indices de Breslow simulés grâce à des fantômes d’épaisseur variant par pas d’1 mm. D’autre part, des mesures de spectroscopie bimodale (combinant autofluorescence en multi-excitation et réflectance diffuse) ont été réalisées sur peau murine tout au long des sept mois de photocarcinogenèse. Des prélèvements cutanés ont permis d’établir trois classes histologiques (en plus de la classe saine du groupe contrôle) : hyperplasie compensatoire, hyperplasie atypique et dysplasie. Puis la précision diagnostique a été évaluée par analyse statistique multivariée. Nos principaux résultats montrent que la bimodalité associant autofluorescence (excitation à 410 nm) et réflectance diffuse permet une amélioration de la spécificité de 9% comparées aux performances de chacune des modalités utilisée seule lors de la discrimination des trois types d’hyperplasie. Des études cliniques doivent maintenant confirmer l’intérêt de ces résultats.Autofluorescence and diffuse reflectance spectroscopies were studied as non-invasive tools to discriminate different stages of skin neoplastic transformation and thus to help diagnose the two most lethal skin lesions: cutaneous melanoma and squamous cell carcinoma. Concerning melanoma, skin phantoms were made to simulate several melanoma thicknesses (Breslow index). Spatially-resolved diffuse reflectance spectroscopy (using five collection optical fibers set at five different distances from the excitation optical fiber) allowed discrimination (p<0.05) of melanoma layers, the thickness of which was 1 mm different. Since diffuse reflectance spectroscopy has already shown good results in assessing malignancy of pigmented skin lesions, such a spectroscopy could be used as a complementary tool of cutaneous melanoma diagnosis. Using ultra-violet induced squamous cell carcinoma of mouse skin, bimodal spectra (multi-excitation fluorescence and diffuse reflectance) were acquired throughout the 7 month-carcinogenesis. Histological sampling followed spectral acquisition and three histological classes were determined by histo-pathological examination: compensatory hyperplasia, atypical hyperplasia and dysplasia. A fourth “healthy” class consisted in the skin sampled on mice that were never irradiated (control group). Multivariate statistical analysis of the spectral data set showed that combining autofluorescence (best results obtained with a 410 nm excitation) and diffuse reflectance resulted in a 9% increase of specificity when discriminating the three types of hyperplasia from one another compared to each modality used alone. Such results need to be confirmed through clinical trials on human patients

Autofluorescence-based redox status as a differential diagnostic parameter of skin carcinomas

International audienc

Ann Pharm Fr

OBJECTIF: A partir des bilans de médication réalisés, analyser les traitements médicamenteux les plus générateurs d’interventions pharmaceutiques et les problèmes qui y sont liés. METHODE: Analyse des rapports de stage des étudiants en 6ème année de pharmacie de l’Université de Bordeaux, promotion 2017-2018. RÉSULTATS: 76 % des bilans partagés de médication ont détecté au moins un problème lié à un médicament dans la population étudiée. Les classes de médicaments qui ont le plus engendré des interventions pharmaceutiques sont les médicaments du système nerveux, les médicaments des voies digestives et métabolisme et les médicaments du système cardiovasculaire. Les problèmes les plus fréquemment rencontrés sont la prescription d’un médicament non justifié, une contre-indication ou une non-conformité aux référentiels et des problèmes de posologie. CONCLUSION: Les médicaments les plus à risque de problèmes et d’interventions pharmaceutiques détectés dans cette étude sont les mêmes que ceux décrits dans la littérature internationale. Ceci tend à montrer que des précautions supplémentaires doivent être déployées pour leur usage chez la personne âgée. De plus, ce nouveau service pharmaceutique est un moyen efficace de les détecter.OBJECTIVE: Using clinical medication reviews, analyze the most pharmaceuticals intervention generating treatments and the problems associated. METHODS: Analysis of activity reports made by 6th year pharmaceutical students from the University of Bordeaux, class of 2017-2018 Results: 76% of clinical medication review have detected at least one drug related problem in the population of this study. Drug classes that most frequently lead to pharmaceutical interventions are nervous system drugs, alimentary tract and metabolisma drugs and cardiovascular system drugs. The most frequent drug related problems are an unjustified prescription, a contraindication or a non-compliance with the standards of care and posology issues. CONCLUSIONS: The most at risk and pharmaceutical intervention generating drugs in this study are the same as described in the international literature. This shows that more precautions must be taken for their use in the elderly. Furthermore, this new pharmaceutical service is an efficient way to detect them

Caractérisation de la transformation néoplasique de la peau par spectroscopies optiques sur fantôme de mélanome et carcinome épidermoïde murin photo-induit

L objectif de ce travail de recherche est d évaluer la capacité des spectroscopies optiques d autofluorescence et de réflectance diffuse à caractériser les différents stades de la transformation néoplasique de la peau et ainsi d aider au diagnostic des deux lésions de peau les plus létales : le mélanome malin et le carcinome épidermoïde. Dans l étude portant sur le mélanome, un objet-test ( fantôme ) a été développé pour modéliser différentes épaisseurs de mélanome (indice de Breslow). La spectroscopie de réflectance diffuse résolue spatialement (grâce à l utilisation de cinq fibres optiques réceptrices situées à cinq distances différentes de la fibre optique excitatrice) a montré sa capacité à discriminer (p<0,05) des indices de Breslow simulés grâce à des fantômes d épaisseur variant par pas d 1 mm. D autre part, des mesures de spectroscopie bimodale (combinant autofluorescence en multi-excitation et réflectance diffuse) ont été réalisées sur peau murine tout au long des sept mois de photocarcinogenèse. Des prélèvements cutanés ont permis d établir trois classes histologiques (en plus de la classe saine du groupe contrôle) : hyperplasie compensatoire, hyperplasie atypique et dysplasie. Puis la précision diagnostique a été évaluée par analyse statistique multivariée. Nos principaux résultats montrent que la bimodalité associant autofluorescence (excitation à 410 nm) et réflectance diffuse permet une amélioration de la spécificité de 9% comparées aux performances de chacune des modalités utilisée seule lors de la discrimination des trois types d hyperplasie. Des études cliniques doivent maintenant confirmer l intérêt de ces résultats.Autofluorescence and diffuse reflectance spectroscopies were studied as non-invasive tools to discriminate different stages of skin neoplastic transformation and thus to help diagnose the two most lethal skin lesions: cutaneous melanoma and squamous cell carcinoma. Concerning melanoma, skin phantoms were made to simulate several melanoma thicknesses (Breslow index). Spatially-resolved diffuse reflectance spectroscopy (using five collection optical fibers set at five different distances from the excitation optical fiber) allowed discrimination (p<0.05) of melanoma layers, the thickness of which was 1 mm different. Since diffuse reflectance spectroscopy has already shown good results in assessing malignancy of pigmented skin lesions, such a spectroscopy could be used as a complementary tool of cutaneous melanoma diagnosis. Using ultra-violet induced squamous cell carcinoma of mouse skin, bimodal spectra (multi-excitation fluorescence and diffuse reflectance) were acquired throughout the 7 month-carcinogenesis. Histological sampling followed spectral acquisition and three histological classes were determined by histo-pathological examination: compensatory hyperplasia, atypical hyperplasia and dysplasia. A fourth healthy class consisted in the skin sampled on mice that were never irradiated (control group). Multivariate statistical analysis of the spectral data set showed that combining autofluorescence (best results obtained with a 410 nm excitation) and diffuse reflectance resulted in a 9% increase of specificity when discriminating the three types of hyperplasia from one another compared to each modality used alone. Such results need to be confirmed through clinical trials on human patients.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Spatially resolved multimodality spectroscopy for in vivo diagnosis of skin precancer: recent developments in data extraction and classification

Session organisée uniquement avec des invités... http://laseroptics.ru/download/LO2012_Technical_Program_final.pdfInternational audienceSome of the most recent developments are presented in multidimensional spectrosocpic data extraction and classification of non- and pre-cancerous skin tissues using Spaatially Resolved Multiple Excitation AutoFluorescence and Diffuse Reflectance Spectroscopie