Noninvasive detection of bladder cancer using mid-infrared spectra classification

International audienceIn this paper, we focus on the detection of Bladder Cancer (BC) via mid infrared spectroscopy. Two main contributions, material and methods, are presented. In terms of material, a new minimally invasive technology, combining fiber evanescent wave spectroscopy and newly patented biosensors, is used for the first time to acquire mid-infrared spectra from voided urine/bladder wash. This new machine promises practicality, cheapness and high-quality of spectrum acquisition. As for classical systems, the data acquired using the new system was highly correlated, resulting in a poor classification performance using classical methods. Therefore, the second contribution consists in developing statistical methods that alleviate the problem. Three new statistical methods based on Partial Least Square Discriminant Analysis algorithm (PLSDA) are proposed. PLSDA is a supervised classifier well-known for its ability to process correlated data. The key point is the choice of the most discriminant latent variables in the training step. In this work, we propose three new decision rules in order to select the most relevant latent variables. These decision rules give rise to three algorithms, namely bayesian, joint and best model PLSDA. A comparative study between the proposed methods and standard ones, namely SVM, K-MEANS and classical PLSDA, confirms clearly the efficiency of the former. The best performance in terms of accuracy is achieved by joint and best model PLSDA (82.35%). Besides, by embedding the proposed statistical methods in the new machine, we are able to provide a new medical device that is very promising in terms of automatic bladder cancer detection

Fabrication of highly homogeneous As2Se3 glass under argon flow

International audienceThe present study relates to a new method for the synthesis of As2Se3 glass in a controlled atmosphere. The advantage of this technique is that it does not require sealing of the silica reaction container and therefore makes it likely to substitute the current industrial batch by batch synthesis which actually needs very expensive single-use sealed silica vessels. An experimental device has been developed for these purposes. It is equipped with a stirring mechanism to homogenize the molten bath. In order to avoid contamination by oxygen and moisture, the synthesis is carried out under argon flow (pressure of 1 bar). Material losses during synthesis can be reduced to less than 2% when temperature is progressively increased up to 430 °C. Bulk glass ingots are finally obtained according to a two-step annealing process. Their chemical composition is analyzed by EDS and shows a variation range of less than 0.2%. The excellent reproducibility of the given method is also confirmed by the refractive indexes, that do not differ for more than 1 * 10−3 from one another. Adverse absorption bands due to oxygen do not occur in the 8-12 μm spectral region when 1000 ppm of Mg is added. As no distilling operation has been carried out until now, the magnesium oxide partially keeps staying in the glass and leads to scattering losses at short wavelengths

Mechanical Alloying and Molding by Spark Plasma Sintering of Telluride based glasses

International audienceAlternative way of synthesis for high refractive index tellurides based glasses has been experimented, in addition to low temperature Spark Plasma Sintering. The composition tested, Ge25Se10Te65, has been chose in the Ge-Se-Te system and characterized. Its index refractive index of 3.12 and overall optical, thermal and mechanical properties makes it the perfect candidate for IR application. However, due to its relative instability regarding crystallization, formation of GeTe crystals occurs during mechanical alloying using raw elements. Transparency has not been achieved in the sintered samples using this powder, as the crystallization rate is accelerated by the pressure during the process. In parallel, glass samples synthesized by melt-quenching have been used to determine optimal sintering parameters for this composition. The main issue met during those tests has been the carbon contamination, reducing overall transparency of the samples through scatterings. As such, it has been shown that the critical parameter to consider to limiting this pollution is the powder granulometry, needing to be above 100 mu m for optimal performance. This shows the potential for this method to produce high refractive index IR optics, using even unstable glasses

Shaping of looped miniaturized chalcogenide fiber sensing heads for mid-​infrared sensing

International audienceChalcogenide glass fibers are promising photonic tools to develop Fiber Evanescent Wave Spectroscopy (FEWS) optical sensors working in the mid-​IR region. Numerous pioneering works have already been carried out showing their efficiency, esp. for bio-​medical applications. Nevertheless, this technol. remains confined to academic studies at the lab. scale because chalcogenide glass fibers are difficult to shape to produce reliable, sensitive and compact sensors. In this paper, a new method for designing and fabricating a compact and robust sensing head with a selenide glass fiber is described. Compact looped sensing heads with diam. equal to 2 mm were thus shaped. This represents an outstanding achievement considering the brittleness of such uncoated fibers. FEWS expts. were implemented using alc. solns. as target samples showing that the sensitivity is higher than with the routinely used classical fiber. It is also shown that the best compromise in term of sensitivity is to fabricate a sensing head including two full loops. From a mech. point of view, the breaking loads of the loop shaped head are also much higher than with classical fiber. Finally, this achievement paves the way for the use of mid-​IR technol. during in situ and even in vivo medical operations. Indeed, is is now possible to slide a chalcogenide glass fiber in the operating channel of a std. 2.8 mm diam. catheter

Early diagnosis of NAFLD-NASH transition using mid infrared spectroscopy.

International audienceNon-alcoholic fatty liver disease (NAFLD) is defined as an excessive accumulation of fat in the liver in the absence of excessive drinking of alcohol. Initially considered as benign and self-limited, NAFLD may progress to the malignant stage of non-alcoholic steatohepatitis (NASH) characterized by degenerate hepatocellular ballooning and lobular inflammation. NASH can lead to hepatic fibrosis and ultimately to cirrhosis and hepatocellular carcinoma. Unfortunately, the transition from NAFLD to NASH is difficult to detect so far. In this paper, we propose to evaluate the characterization of NASH using mid infrared fiber evanescent wave spectroscopy on blood serum. We used an heuristic variable selection method and a generalized linear model to classify NAFLD and NASH spectra. The obtained results proved that this technique is a promising non-invasive and simple diagnosis tool for NASH

Mid-infrared spectroscopy of serum, a promising non-invasive method to assess prognosis in patients with ascites and cirrhosis.

Prognostic tests are critical in the management of patients with cirrhosis and ascites. Biological tests or scores perform poorly in that situation. Mid-infrared fibre evanescent wave spectroscopy (MIR-FEWS) which allows for global serum metabolic profiling may provide more relevant information by measuring a wider range of metabolic parameters in serum. Here we present the accuracy of a MIR-FEWS based predictive model for the prognosis of 6 months survival in patients with ascites and cirrhosis.Patients with ascites were prospectively included and followed up for 6 months. MIR-FEWS spectra were measured in serum samples. The most informative spectral variables obtained by MIR-FEWS were selected by FADA algorithm and then used to build the MIR model. Accuracy of this model was assessed by ROC curves and 90%/10% Monte Carlo cross-validation. MIR model accuracy for 6 months survival was compared to that of the Child-Pugh and MELD scores.119 patients were included. The mean age was 57.36±13.70, the MELD score was 16.32±6.26, and the Child-Pugh score was 9.5±1.83. During follow-up, 23 patients died (20%). The MIR model had an AUROC for 6 months mortality of 0.90 (CI95: 0.88-0.91), the MELD 0.77 (CI95: 0.66-0.89) and Child-Pugh 0.76 (CI95: 0.66-0.88). MELD and Child-Pugh AUROCs were significantly lower than that of the MIR model (p = 0.02 and p = 0.02 respectively). Multivariate logistic regression analysis showed that MELD (p<0.05, OR:0.86;CI95:0.76-0.97), Beta blockers (p = 0.036;OR:0.20;CI95:0.04-0.90), and the MIR model (p<0.001; OR:0.50; CI95:0.37-0.66), were significantly associated with 6 months mortality.In this pilot study MIR-FEWS more accurately assess the 6-month prognosis of patients with ascites and cirrhosis than the MELD or Child-Pugh scores. These promising results, if confirmed by a larger study, suggest that mid infrared spectroscopy could be helpful in the management of these patients

Selenide and telluride glasses for mid-​infrared bio-​sensing

International audienc

Fast and Non-Invasive Medical Diagnostic Using Mid Infrared Sensor: The AMNIFIR Project

International audienceAim Amnifir project, part of the ANR TECSAN program, intended to assess the capabilities of a new Mid InfraRed spectroscopy (MIR) device. It used a simple fiber optic sampling method: Fiber Evanescent Wave Spectroscopy (FEWS), which makes Point of Care applications possible and delivers a result within a few minutes. Material and method To investigate the technology application range, different biological media (tissues, fluids) as well as pathologies (chronic, cancerous) were considered during the project. We present work on one cancer diagnostic, measuring tissues (colorectal polyp examination), and one chronic disease diagnostic, using a fluid sample (Non-Alcoholic SteatoHepatitis (NASH) markers in serum). We used specific FEWS sensors for both cases, made of chalcogenide infrared glass fiber, as well as proper signal analysis algorithm that first selected spectra area of interest by genetic algorithm, then discriminated the healthy population from the sick one by linear discriminant analysis. Results Measurements using liquid samples provide very encouraging results for NASH identification. On other hand, fiber sensor proved more difficult to use on tissues, as the fiber mechanical resistance appeared too low to sustain a contact with the hardest polyps. Conclusions AMNIFIR project demonstrated capabilities of MIR FEWS for medical diagnostic using biological fluids, leading to recruitments of further cohorts of NASH and other hepatic disorders patients. Mechanical resistance of fiber needs to be improved for tissues diagnostic

Ruling out septic arthritis risk in a few minutes using mid-infrared spectroscopy in synovial fluids

International audienceObjectives: The aim of this study was to show the usefulness of a mid-infrared fibre evanescent wave spectroscopy point of care device in the identification of septic arthritis patients in a multicentre cohort, and to apply this technology to clinical practice among physicians.Methods: SF samples from 402 patients enrolled in a multicentre cohort were frozen for analysis by mid-infrared fibre evanescent wave spectroscopy. The calibration cohort was divided into two groups of patients (septic arthritis and non-septic arthritis) and relevant spectral variables were used for logistic regression model. Model performances were tested on an independent set of 86 freshly obtained SF samples from patients enrolled in a single-centre acute arthritis cohort and spectroscopic analyses performed at the patient’s bedside.Results:The model set-up, using frozen–thawed SFs, provided good performances, with area under the curve 0.95, sensitivity 0.90, specificity 0.90, positive predictive value 0.41 and negative predictive value 0.99. Performances obtained in the validation cohort were area under the curve 0.90, sensitivity 0.92, specificity 0.81, positive predictive value 0.46 and negative predictive value 0.98. The septic arthritis probability has been translated into a risk score from 0 to 4 according to septic risk. For a risk score of 0, the probability of identifying a septic patient is very low (negative predictive value of 1), whereas a risk score of 4 indicates very high risk of septic arthritis (positive predictive value of 1).Conclusion:Mid-infrared fibre evanescent wave spectroscopy could distinguish septic from non-septic synovial arthritis fluids with good performances, and showed particular usefulness in ruling out septic arthritis. Our data supports the possibility of technology transfe

Fabrication of chalcogenide microstructured optical preforms and fibers by additive manufacturing of chalcogenide glasses

International audienceIn recent years, a growing interest has settled for optical materials and fibers for the mid infrared (mid-IR) region. This interest originates from societal needs for health and environment for instance, and also from demand for defence applications. Indeed, the mid-IR spectral region contains the atmospheric transparent windows (3-5 µm) and (8-12 µm) where thermal imaging (military and civilian) can take place. The elaboration of chalcogenide microstructured optical fibers (MOFs) permits to combine the mid infrared transmission of chalcogenide glasses up to 18 µm to the unique optical properties of MOFs thanks to the high degree of freedom in the design of their geometrical structure. In this context, additive manufacturing of glass materials appears as an attractive technique to achieve more elaborate designs that can hardly be obtain using more common methods such as the stack-and-draw or molding. Taking advantages of the specific physical properties of chalcogenide glasses such as low Tg and extrusion temperature, we have shown that chalcogenide preforms can be rapidly obtained by fused deposition modeling (FDM) using a customized RepRap-style 3D printed fed with chalcogenide glass rods. Such as-prepared preforms can be drawn into chalcogenide optical fibers. Those early-stage results open a new way for the elaboration of chalcogenide MOFs