Mid-Infrared Spectroscopy as a New Tool for Ruling Out Spontaneous Bacterial Peritonitis: A Proof-of-Concept Study.

BACKGROUND AND AIMS: A highly sensitive and specific point-of-care method for diagnosing spontaneous bacterial peritonitis (SBP) is currently lacking. The objective of the present study is to evaluate the diagnostic value of a rapid, easy-to-use, mid-infrared fiber evanescent wave spectroscopy (MIR-FEWS) method for ruling out SBP. PATIENTS AND METHODS: Cirrhotic patients (n = 256) at five centers in France were included for suspected SBP or for the scheduled evacuation of ascites fluid. The mid-infrared spectrum of 7 µL of an ascites fluid sample was recorded using a MIR-FEWS system. To define a model for the diagnosis of SBP, the patients were divided into a calibration group (n = 170) and a validation group (n = 86). RESULTS: Most of the patients were male (71%). The mean age was 60.25 years. Alcohol-related liver disease was the most common cause of cirrhosis. SBP was observed in 18% of the patients. For the diagnosis of SBP in the calibration and validation groups, respectively, the model gave areas under the receiver operating characteristic curves of 0.87 and 0.89, sensitivities of 90% and 87%, specificities of 78% and 80%, positive predictive values of 48% and 50%, negative predictive values of 97% and 96%, positive likelihood ratio of 4.09 and 4.35, negative likelihood ratio of 0.13 and 0.16, Youden index of 0.68 and 0.67, and correct classification rates of 80% and 81%. CONCLUSION: The results of this proof-of-concept study show that MIR-FEWS is a highly sensitive diagnostic method for ruling out SBP. The method warrants further investigation.

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

OBJECTIVES: 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 transfer. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02860871.

The mid-infrared spectroscopy: A novel non-invasive diagnostic tool for NASH diagnosis in severe obesity.

There is an urgent medical need to develop non-invasive tests for non-alcoholic steatohepatitis (NASH). This study evaluates the diagnostic performance of an innovative model based on mid-infrared (MIR) spectroscopy for the diagnosis of NASH. METHODS: Severely obese patients who underwent a bariatric procedure at the University Hospital of Nice, France (n = 395) were prospectively recruited. The clinico-biological characteristics were measured prior to surgery. Liver biopsies were collected during the surgical procedure and assessed by a pathologist. A training group (316 patients, NASH: 16.8%) and a validation group (79 patients, NASH: 16.5%) were randomly defined. MIR spectra were acquired by fiber evanescent wave spectroscopy, using chalcogenide glass fiber optic sensors and a spectrometer. This absorption spectroscopic technique delivers a spectrum that identifies the molecular composition of a sample, defining a patient's metabolic fingerprint. RESULTS: The areas under the receiver operating curve (AUROC) for the diagnosis of NASH were 0.82 and 0.77 in the training and validation groups, respectively. The best threshold was 0.15, which was associated with a sensitivity of 0.75 and 0.69, and a specificity of 0.72 and 0.76. Negative predictive values of 0.94 and 0.93 and positive predictive values of 0.35 and 0.36, as well as correctly classified patient rates of 72% and 75% were obtained in the training and validation groups, respectively. A composite model using aspartate aminotransferase level, triglyceride level and waist circumference alongside the MIR spectra led to an increase in AUROC (0.88 and 0.84 for the training and validations groups, respectively). CONCLUSIONS: MIR spectroscopy provides good sensitivity and negative predictive values for NASH screening in patients with severe obesity. LAY SUMMARY: There is an urgent need for tools to non-invasively diagnose and monitor non-alcoholic steatohepatitis (NASH). This study evaluates the performance of a new tool for fast NASH diagnosis based on mid-infrared (MIR) spectroscopy. Using serum samples from severely obese patients who underwent a bariatric procedure, which enabled a concomitant liver biopsy to be performed, the MIR spectroscopy model performed well in screening patients for NASH compared to a traditional, histological diagnosis.

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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

Non-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.

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

Chalcogenide glass fibers are promising photonic tools to develop Fiber Evanescent Wave Spectroscopy (FEWS) optical sensors working in the mid-infrared region. Numerous pioneering works have already been carried out showing their efficiency, especially for bio-medical applications. Nevertheless, this technology remains confined to academic studies at the laboratory 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 diameter equal to 2 mm were thus shaped. This represents an outstanding achievement considering the brittleness of such uncoated fibers. FEWS experiments were implemented using alcoholic solutions 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 mechanical 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-infrared technology 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 standard 2.8 mm diameter catheter.