Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma.

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins-complete tumor removal while attempting to preserve viable tissue-remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

Raman spectroscopy and U-Net deep neural network in antiresorptive drug-related osteonecrosis of the jaw.

OBJECTIVE: Application of an optical method for the identification of antiresorptive drug-related osteonecrosis of the jaw (ARONJ). METHODS: We introduce shifted-excitation Raman difference spectroscopy followed by U-Net deep neural network refinement to determine bone tissue viability. The obtained results are validated through established histological methods. RESULTS: Discrimination of osteonecrosis from physiological tissues was evaluated at 119 distinct measurement loci in 40 surgical specimens from 28 patients. Mean Raman spectra were refined from 11,900 raw spectra, and characteristic peaks were assigned to their respective molecular origin. Then, following principal component and linear discriminant analyses, osteonecrotic lesions were distinguished from physiological tissue entities, such as viable bone, with a sensitivity, specificity, and overall accuracy of 100%. Moreover, bone mineral content, quality, maturity, and crystallinity were quantified, revealing an increased mineral-to-matrix ratio and decreased carbonate-to-phosphate ratio in ARONJ lesions compared to physiological bone. CONCLUSION: The results demonstrate feasibility with high classification accuracy in this collective. The differentiation was determined by the spectral features of the organic and mineral composition of bone. This merely optical, noninvasive technique is a promising candidate to ameliorate both the diagnosis and treatment of ARONJ in the future.

Optical diagnosis of oral cavity lesions by label-free Raman spectroscopy.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers and frequently preceded by non-malignant lesions. Using Shifted-Excitation Raman Difference Spectroscopy (SERDS), principal component and linear discriminant analysis in native tissue specimens, 9500 raw Raman spectra of OSCC, 4300 of non-malignant lesions and 4200 of physiological mucosa were evaluated. Non-malignant lesions were distinguished from physiological mucosa with a classification accuracy of 95.3% (95.4% sensitivity, 95.2% specificity, area under the curve (AUC) 0.99). Discriminating OSCC from non-malignant lesions showed an accuracy of 88.4% (93.7% sensitivity, 76.7% specificity, AUC 0.93). OSCC was identified against physiological mucosa with an accuracy of 89.8% (93.7% sensitivity, 81.0% specificity, AUC 0.90). These findings underline the potential of SERDS for the diagnosis of oral cavity lesions.

Vapor-Liquid Equilibria of Mixtures Containing Ethanol, Oxygen, and Nitrogen at Elevated Pressure and Temperature, Measured with In Situ Raman Spectroscopy in Microcapillaries.

Ethanol and oxygen containing gases are mixed in a T-junction at elevated pressure and then passed into a fused silica microcapillary, located in a heating block. Inside the microcapillary a Taylor flow of alternating liquid and vapor segments is formed. The thermodynamic equilibrium composition of the liquid and vapor segment depends on pressure and temperature. Their compositions are measured inside the microcapillary using in situ Raman spectroscopy. The main results obtained therefrom are temperature-composition (Tx) diagrams at conditions relevant for combustion engines [p = (3 to 8) MPa; T = (303 to 473) K]. Isothermal vapor-liquid equilibria (VLE) data are derived and given in pressure-composition (px) diagrams. The investigation of different gas mixtures containing oxygen and nitrogen allows furthermore the illustration of VLE data at constant pressure and temperature in ternary diagrams. The obtained results are compared to scarce literature data. An equation of state (Peng-Robinson EOS) is furthermore adjusted to the measured results.

Raman Spectroscopic Study of the Effect of Aqueous Salt Solutions on the Inhibition of Carbon Dioxide Gas Hydrates.

We present an experimental Raman study on the thermodynamic inhibition effect of different salts (NaCl, KCl, MgCl2, and CaCl2 from 2.5 to 11 wt %) on the formation of carbon dioxide gas hydrates. We performed the experiments in a high-pressure vessel with two phases: a water-rich phase and a CO2-rich phase. We investigated the changes the inhibitors induce in the water-rich phase before the onset of hydrate formation. This includes a study of the change in molar reaction enthalpy between strongly and weakly hydrogen-bonded water and the decrease in solubility of carbon dioxide in water. Additionally, the growth mechanisms of carbon dioxide hydrates were investigated by determining the amount of solid hydrates formed and the reaction constant. The results show that the molar reaction enthalpy, the solubility of CO2, and the amount of solid hydrates formed can be correlated with the effective mole fraction, whereas the reaction constant is not affected by the addition of salts. The decrease of the molar reaction enthalpy can be directly correlated with the equilibrium temperature of the gas hydrates.

Raman Thermometry in Water, Ethanol, and Ethanol/Nitrogen Mixtures from Ambient to Critical Conditions.

We present investigations into remote liquid temperature sensing with Raman spectroscopy using different evaluation methods for the OH stretching vibration band. Water, ethanol, and ethanol saturated with nitrogen, all as liquids or liquid-like supercritical fluids, are pumped through a heated microcapillary system at elevated pressures. Raman spectra are recorded from the liquid inside the microcapillary and are evaluated with respect to the temperature sensitivity of the OH stretching vibration. The four approaches applied are (i) to evaluate the center position of the Raman OH-band, (ii) the integrated absolute difference spectrum, (iii) the intensity ratio of two regions of the OH-band, and (iv) the intensity ratio of two fitted Gaussian peaks. The temperature range investigated covers from ambient temperature to the component's respective boiling temperature or critical temperature at sub- and supercritical pressures. Precision and robustness of the employed methods are characterized. It is shown that two out of the four methods feature temperature deviations smaller than 5 K at all pressures and that one method can also be applied to liquid mixtures of ethanol and nitrogen. Applicability to other liquids and mixtures is discussed.

Temperature determination of superheated water vapor by rotational-vibrational Raman spectroscopy.

We present a novel non-invasive laser-based tool for tracer-free spatially resolved temperature measurement in superheated water vapor at atmospheric pressure. The technique exploits the temperature sensitivity of the rotational-vibrational Raman spectrum of the v1 stretching vibration. This Letter demonstrates the Raman sensor, its application to a steam gasification reactor, and four methods to analyze the Raman spectra in order to obtain the temperature: an equal intensity point approach, a pseudo-isosbestic point approach, and two approaches based on the reconstruction of the Raman band by Gaussian/Lorentzian profiles. The evaluated water vapor temperatures inside a reactor for plasma-assisted gasification are compared to data acquired by supercontinuum absorption spectroscopy.

Influence of Sodium Chloride on the Formation and Dissociation Behavior of CO2 Gas Hydrates.

We present an experimental study on the formation and dissociation characteristics of carbon dioxide (CO2) gas hydrates using Raman spectroscopy. The CO2 hydrates were formed from sodium chloride/water solutions with salinities of 0-10 wt %, which were pressurized with liquid CO2 in a stirred vessel at 6 MPa and a subcooling of 9.5 K. The formation of the CO2 hydrate resulted in a hydrate gel where the solid hydrate can be considered as the continuous phase that includes small amounts of a dispersed liquid water-rich phase that has not been converted to hydrate. During the hydrate formation process we quantified the fraction of solid hydrate, xH, and the fraction of the dispersed liquid water-rich phase, xL, from the signature of the hydroxyl (OH)-stretching vibration of the hydrate gel. We found that the fraction of hydrate xH contained in the hydrate gel linearly depends on the salinity of the initial liquid water-rich phase. In addition, the ratio of CO2 and water was analyzed in the liquid water-rich phase before hydrate formation, in the hydrate gel during growth and dissociation, and after its complete dissociation again in the liquid water-rich phase. We observed a supersaturation of CO2 in the water-rich phase after complete dissociation of the hydrate gel and were able to show that the excess CO2 exists as dispersed micro- or nanoscale liquid droplets in the liquid water-rich phase. These residual nano- and microdroplets could be a possible explanation for the so-called memory effect.

How Sodium Chloride Salt Inhibits the Formation of CO2 Gas Hydrates.

We present an experimental Raman study on how the addition of sodium chloride to CO2-hydrate-forming systems inhibits the hydrate formation thermodynamically. For this purpose, the molar enthalpy of reaction and the molar entropy of reaction for the reaction of weakly hydrogen-bonded water molecules to strongly hydrogen bonded water molecules are determined for different salinities from the Raman spectrum of the water-stretching vibration. Simultaneously, the influence of the salinity on the solubility of CO2 in the liquid water-rich phase right before the start of hydrate formation is analyzed. The results demonstrate that various mechanisms contribute to the inhibition of gas hydrate formation. For the highest salt concentration of 20 wt % investigated, the temperature of gas hydrate formation is lowered by 12 K. For this concentration the molar enthalpy and entropy of reaction become smaller by 50 and 20%, respectively. Concurrently, the solubility of carbon dioxide is reduced by 70%. These results are compared with data in literature for systems of sodium chloride in water (without carbon dioxide).