Optical cavity spectroscopy using heterodyne detection with optical feedback laser frequency locking.

We demonstrate an accurate high sensitivity method for cavity spectroscopy. We measure the frequency intervals of transverse electromagnetic modes relative to a fundamental mode in a high finesse optical resonator, and attribute their mode numbers unambiguously. A laser is frequency locked to a fundamental T E M 00 cavity mode by optical feedback, and phase modulation is used to obtain frequency side bands, which may come to resonance with other transverse cavity modes as the radio-frequency of the modulation is tuned. At these resonances, transmission of the side bands is sensitively detected by heterodyning with the carrier. We also analyze the transverse spatial profile of the heterodyne signal for identification of mode numbers. The adjustment of the Gaussian cavity model to the measured frequency intervals yields values of cavity length, mirror radius of curvature, and mirror ellipticity, with high precision to the ppm level.

Continuous Endogenous Exhaled CO Monitoring by Laser Spectrometer in Human EVLP Before Lung Transplantation.

Endogenous production of carbon monoxide (CO) is affected by inflammatory phenomena and ischemia-reperfusion injury. Precise measurement of exhaled endogenous CO (eCO) is possible thanks to a laser spectrometer (ProCeas® from AP2E company). We assessed eCO levels of human lung grafts during the normothermic Ex-Vivo Lung Perfusion (EVLP). ProCeas® was connected in bypass to the ventilation circuit. The surgical team took the decision to transplant the lungs without knowing eCO values. We compared eCO between accepted and rejected grafts. EVLP parameters and recipient outcomes were also compared with eCO values. Over 7 months, eCO was analyzed in 21 consecutive EVLP grafts. Two pairs of lungs were rejected by the surgical team. In these two cases, there was a tendency for higher eCO values (0.358 ± 0.52 ppm) compared to transplanted lungs (0.240 ± 0.76 ppm). During the EVLP procedure, eCO was correlated with glucose consumption and lactate production. However, there was no association of eCO neither with edema formation nor with the PO2/FiO2 ratio per EVLP. Regarding post-operative data, every patient transplanted with grafts exhaling high eCO levels (>0.235 ppm) during EVLP presented a Primary Graft Dysfunction score of 3 within the 72 h post-transplantation. There was also a tendency for a longer stay in ICU for recipients with grafts exhaling high eCO levels during EVLP. eCO can be continuously monitored during EVLP. It could serve as an additional and early marker in the evaluation of the lung grafts providing relevant information for post-operative resuscitation care.

Laser spectroscopy for breath analysis: towards clinical implementation.

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.

Nitric Oxide Analysis Down to ppt Levels by Optical-Feedback Cavity-Enhanced Absorption Spectroscopy.

Monitoring nitric oxide at the trace level is required in a large range of applications. We report on a trace gas analyzer optimized for nitric oxide measurements by Optical Feedback Cavity Enhanced Absorption Spectroscopy with an interband cascade laser at 5.3 µm. The short response time of the instrument allows for reaching the level of 50 ppt in only 180 ms. Its stability enables averaging up to 12 min to reach a detection limit of 0.9 ppt. Absolute concentration calibration requires to account for the optical saturation effect that results from the intense absorption line intensity addressed here, in the mid infrared region, in contrast to instruments that are operating in the near infrared region.

Frequency comb based spectrometer for in situ and real time measurements of IO, BrO, NO2, and H2CO at pptv and ppqv levels.

We report an instrument designed for trace gas measurement of highly reactive halogenated radicals, such as bromine oxide and iodine oxide, as well as for nitrogen dioxide and formaldehyde. This compact and robust spectrometer relies on an alternated injection of a frequency-doubled femtosecond radiation at 338 and 436 nm into two parallel high-finesse cavities, for measuring BrO + H(2)CO, and IO + NO(2), respectively. The transmission of the broadband radiation through the cavity is analyzed with a high resolution, compact spectrograph consisting of an echelle grating and a high sensitivity CCD camera. The transportable instrument fits on a breadboard 120 × 60 cm size and is suitable for in situ and real time measurements of these species. A field campaign at the Marine Boundary Layer in Roscoff (in the northwest of France, 48.7°N, 4.0°W) during June 2011 illustrates the outstanding performance of the instrument, which reaches a bandwidth normalized minimum absorption coefficient of 1.3 × 10(-11) cm(-1) Hz(-1/2) per spectral element, and provides detection levels as low as 20 parts per quadrillion of IO in 5 min of acquisition.

Monitoring of endogenous nitric oxide exhaled by pig lungs during ex-vivo lung perfusion.

In the context of organ shortage for transplantation, new criteria for better organ evaluation should be investigated. Ex-vivo lung perfusion (EVLP) allows extra-corporal lung re-conditioning and evaluation, under controlled parameters of the organ reperfusion and mechanical ventilation. This work reports on the interest of exhaled gas analysis during the EVLP procedure. After a 1 h cold ischemia, the endogenous gas production by an isolated lung of nitric oxide and carbon monoxide is simultaneously monitored in real time. The exhaled gas is analysed with two very sensitive and selective laser spectrometers developed upon the technique of optical-feedback cavity-enhanced absorption spectroscopy. Exhaled gas concentration measured for an ex-vivo lung is compared to the corresponding production by the whole living pig, measured before euthanasia. On-line measurements of the fraction of nitric oxide in exhaled gas (FENO) in isolated lungs are reported here for the first time, allowing to resolve the respiratory cycles. In this study, performed on 9 animals, FENO by isolated lungs range from 3.3 to 10.6 ppb with a median value of 4.4 ppb. Pairing ex-vivo lung and pig measurements allows to demonstrate a systematic increase of FENO in the ex-vivo lung as compared to the living animal, by a factor of 3 ± 1.2. Measurements of the fraction of carbon monoxide in exhaled gas (FECO) confirm levels recorded during previous studies driven to evaluate FECO as a potential marker of ischemia reperfusion injuries. FECO production by ex-vivo lungs ranges from 0.31 to 2.3 ppm with a median value of 0.8 ppm. As expected, these FECO values are lower than the production by the corresponding whole pig body, by a factor of 6.9 ± 2.7.

High inhaled oxygen concentration quadruples exhaled CO in healthy volunteers monitored by a highly sensitive laser spectrometer.

Carbon monoxide (CO) monitoring in human breath is the focus of many investigations as CO could possibly be used as a marker of various diseases. Detecting CO in human breath remains a challenge because low concentrations (

Exhaled carbon monoxide is correlated with ischemia reperfusion injuries during ex vivo lung perfusion in pigs.

Measurement of exhaled carbon monoxide (eCO) might help in the selection of lung grafts during ex vivo lung perfusion (EVLP) since its endogenous production is increased under ischemia reperfusion. The objective of this study was to measure eCO variations depending on the extent of lung ischemia reperfusion injuries. Using a porcine model and a laser spectrometer instrument, eCO was measured during EVLP. eCO was compared after 30 min (D0) or 24 h (D1) of cold ischemia. The ability of eCO to distinguish lungs deemed suitable for transplantation was evaluated. Six lungs were studied at D0 and compared to six lungs studied at D1. eCO was systematically higher on D1 (1.35 ± 0.26 ppmv versus 0.95 ± 0.31 ppmv, p = 0.01). The best threshold concentration for eCO to select lungs was 0.86 ppmv (area under the receiver operating characteristic curve: 0.65 [95% confidence interval: 0.34-0.97], p = 0.40). These results show that eCO varies during EVLP. The interpretation of this variation and the role of eCO as a biomarker of ischemia reperfusion injuries during EVLP should be tested in further clinical studies.

Real-time measurements of endogenous carbon monoxide production in isolated pig lungs.

Ischemia-reperfusion injuries are a critical determinant of lung transplantation success. The endogenous production of carbon monoxide (CO) is triggered by ischemia-reperfusion injuries. Our aim was, therefore, to assess the feasibility of exhaled CO measurements during the ex vivo evaluation of lungs submitted to ischemia-reperfusion injuries. Five pigs were euthanized and their lungs removed after pneumoplegia. After cold storage (30 min, 4°C), the lungs were connected to an extracorporeal membrane oxygenation circuit, slowly warmed-up, and ventilated. At the end of a 45-min steady state, CO measurements were performed by optical-feedback cavity-enhanced absorption spectroscopy, a specific laser-based technique for noninvasive and real-time low gas concentration measurements. Exhaled CO concentration from isolated lungs reached 0.45±0.19 ppmv and was above CO concentration in ambient air and in medical gas. CO variations peaked during the expiratory phase. Changes in CO concentration in ambient air did not alter CO concentrations in isolated lungs. Exhaled CO level was also found to be uncorrelated to heme oxygenase (HO-1) gene expression. These results confirm the feasibility of accurate and real-time CO measurement in isolated lungs. The presented technology could help establishing the exhaled CO concentration as a biomarker of ischemia-reperfusion injury in ex vivo lung perfusion.