Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

High contrast breast cancer biomarker semi-quantification and immunohistochemistry imaging using upconverting nanoparticles.

Breast cancer is the second leading cause of cancer death in women. Current clinical treatment stratification practices open up an avenue for significant improvements, potentially through advancements in immunohistochemistry (IHC) assessments of biopsies. We report a high contrast upconverting nanoparticles (UCNP) labeling to distinguish different levels of human epidermal growth factor receptor 2 (HER2) in HER2 control pellet arrays (CPAs) and HER2-positive breast cancer tissue. A simple Fourier transform algorithm trained on CPAs was sufficient to provide a semi-quantitative HER2 assessment tool for breast cancer tissues. The UCNP labeling had a signal-to-background ratio of 40 compared to the negative control.

Hybrid heterogeneous phantoms for biomedical applications: a demonstration to dosimetry validation.

Phantoms simultaneously mimicking anatomical and optical properties of real tissues can play a pivotal role for improving dosimetry algorithms. The aim of the paper is to design and develop a hybrid phantom model that builds up on the strengths of solid and liquid phantoms for mimicking various anatomical structures for prostate cancer photodynamic therapy (PDT) dosimetry validation. The model comprises of a photosensitizer-embedded gelatin lesion within a liquid Intralipid prostate shape that is surrounded by a solid silicone outer shell. The hybrid phantom was well characterized for optical properties. The final assembled phantom was also evaluated for fluorescence tomographic reconstruction in conjunction with SpectraCure's IDOSE software. The developed model can lead to advancements in dosimetric evaluations. This would improve PDT outlook as a clinical treatment modality and boost phantom based standardization of biophotonic devices globally.

Extended-wavelength diffuse reflectance spectroscopy dataset of animal tissues for bone-related biomedical applications.

Diffuse reflectance spectroscopy (DRS) has been extensively studied in both preclinical and clinical settings for multiple applications, notably as a minimally invasive diagnostic tool for tissue identification and disease delineation. In this study, extended-wavelength DRS (EWDRS) measurements of ex vivo tissues ranging from ultraviolet through visible to the short-wave infrared region (355-1919 nm) are presented in two datasets. The first dataset contains labelled EWDRS measurements collected from bone cement samples and ovine specimens including 10 tissue types commonly encountered in orthopedic surgeries for data curation purposes. The other dataset includes labelled EWDRS measurements of primarily bone structures at different depths during stepwise drilling into intact porcine skulls until plunging into the cranial cavity. The raw data with code for pre-processing and calibration is publicly available for reuse on figshare. The datasets can be utilized not only for exploratory purposes in machine learning model construction, but also for knowledge discovery in the orthopedic domain to identify important features for surgical guidance, extract physiological parameters and provide diagnostic insights.

Laser absorption spectroscopy measurements of different pulmonary oxygen gas concentrations in transmittance and remittance geometry: phantom study.

Significance: The gas in scattering media absorption spectroscopy (GASMAS) technique has the potential for continuous, clinical monitoring of preterm infant lung function, removing the need for X-ray diagnosis and reliance on indirect and relatively slow measurement of blood oxygenation. Aim: We aim to determine the optimal source-detector configuration for reliable pathlength calculation and to estimate the oxygen gas concentration inside the lung cavities filled with humidified gas with four different oxygen gas concentrations ranging between 21% and 100%. Approach: Anthropomorphic optical phantoms of neonatal thorax with two different geometries were used to acquire GASMAS signals, for 30 source-detector configurations in transmittance and remittance geometry of phantoms in two sizes. Results: The results show that an internal light administration is more likely to provide a high GASMAS signal-to-noise ratio (SNR). In general, better SNRs were obtained with the smaller set of phantoms. The values of pathlength and O2 concentrations calculated with signals from the phantoms with optical properties at 820 nm exhibit higher variations than signals from the phantoms with optical properties at 764 nm. Conclusion: Our study shows that, by moving the source and detector over the thorax, most of the lung volumes can potentially be assessed using the GASMAS technique.

Diffuse reflectance spectroscopy for colorectal cancer surgical guidance: towards real-time tissue characterization and new biomarkers.

Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide, representing 11.3% of the diagnosed cancer cases and resulting in 10.2% (0.88 million) of the cancer related deaths in 2020. CRCs are typically detected at the late stage, which leads to high mortality and morbidity. Mortality and poor prognosis are partially caused by cancer recurrence and postoperative complications. Patient survival could be increased by improving precision in surgical resection using accurate surgical guidance tools based on diffuse reflectance spectroscopy (DRS). DRS enables real-time tissue identification for potential cancer margin delineation through determination of the circumferential resection margin (CRM), while also supporting non-invasive and label-free approaches for laparoscopic surgery to avoid short-term complications of open surgery as suitable. In this study, we have estimated the scattering properties and chromophore concentrations based on 2949 DRS measurements of freshly excised ex vivo specimens of 47 patients, and used this estimation to classify normal colorectal wall (CW), fat and tumor tissues. DRS measurements were performed with fiber-optic probes of 630 µm source-detector distance (SDD; probe 1) and 2500 µm SDD (probe 2) to measure tissue layers ∼0.5-1 mm and ∼0.5-2 mm deep, respectively. By using the 5-fold cross-validation of machine learning models generated with the classification and regression tree (CART) algorithm, we achieved 95.9 ± 0.7% sensitivity, 98.9 ± 0.3% specificity, 90.2 ± 0.4% accuracy, and 95.5 ± 0.3% AUC for probe 1. Similarly, we achieved 96.9 ± 0.8% sensitivity, 98.9 ± 0.2% specificity, 94.0 ± 0.4% accuracy, and 96.7 ± 0.4% AUC for probe 2.

Frameworks of wavelength selection in diffuse reflectance spectroscopy for tissue differentiation in orthopedic surgery.

Significance: Wavelength selection from a large diffuse reflectance spectroscopy (DRS) dataset enables removal of spectral multicollinearity and thus leads to improved understanding of the feature domain. Feature selection (FS) frameworks are essential to discover the optimal wavelengths for tissue differentiation in DRS-based measurements, which can facilitate the development of compact multispectral optical systems with suitable illumination wavelengths for clinical translation. Aim: The aim was to develop an FS methodology to determine wavelengths with optimal discriminative power for orthopedic applications, while providing the frameworks for adaptation to other clinical scenarios. Approach: An ensemble framework for FS was developed, validated, and compared with frameworks incorporating conventional algorithms, including principal component analysis (PCA), linear discriminant analysis (LDA), and backward interval partial least squares (biPLS). Results: Via the one-versus-rest binary classification approach, a feature subset of 10 wavelengths was selected from each framework yielding comparable balanced accuracy scores (PCA: 94.8±3.47%, LDA: 98.2±2.02%, biPLS: 95.8±3.04%, and ensemble: 95.8±3.16%) to those of using all features (100%) for cortical bone versus the rest class labels. One hundred percent balanced accuracy scores were generated for bone cement versus the rest. Different feature subsets achieving similar outcomes could be identified due to spectral multicollinearity. Conclusions: Wavelength selection frameworks provide a means to explore domain knowledge and discover important contributors to classification in spectroscopy. The ensemble framework generated a model with improved interpretability and preserved physical interpretation, which serves as the basis to determine illumination wavelengths in optical instrumentation design.

Mobile multi-configuration clinical translational Raman system for oral cancer application.

Early diagnosis of oral cancer is critical to improve the survival rate of patients. Raman spectroscopy, a non-invasive spectroscopic technique, has shown potential in identifying early-stage oral cancer biomarkers in the oral cavity environment. However, inherently weak signals necessitate highly sensitive detectors, which restricts widespread usage due to high setup costs. In this research, the fabrication and assembly of a customised Raman system that can adapt three different configurations for the in vivo and ex vivo analysis is reported. This novel design will help in reducing the cost required to have multiple Raman instruments specific for a given application. First, we demonstrated the capability of a customized microscope for acquiring Raman signals from a single cell with high signal-to-noise ratio. Generally, when working with liquid samples with low concentration of analytes (such as saliva) under a microscope, excitation light interacts with a small sample volume, which may not be representative of whole sample. To address this issue, we have designed a novel long-path transmission set-up, which was found to be sensitive towards low concentration of analytes in aqueous solution. We further demonstrated that the same Raman system can be incorporated with the multimodal fibre optical probe to collect in vivo data from oral tissues. In summary, this flexible, portable, multi-configuration Raman system has the potential to provide a cost-effective solution for complete screening of precancer oral lesions.

Label-Free Optical Spectroscopy for Early Detection of Oral Cancer.

Oral cancer is the 16th most common cancer worldwide. It commonly arises from painless white or red plaques within the oral cavity. Clinical outcome is highly related to the stage when diagnosed. However, early diagnosis is complex owing to the impracticality of biopsying every potentially premalignant intraoral lesion. Therefore, there is a need to develop a non-invasive cost-effective diagnostic technique to differentiate non-malignant and early-stage malignant lesions. Optical spectroscopy may provide an appropriate solution to facilitate early detection of these lesions. It has many advantages over traditional approaches including cost, speed, objectivity, sensitivity, painlessness, and ease-of use in clinical setting for real-time diagnosis. This review consists of a comprehensive overview of optical spectroscopy for oral cancer diagnosis, epidemiology, and recent improvements in this field for diagnostic purposes. It summarizes major developments in label-free optical spectroscopy, including Raman, fluorescence, and diffuse reflectance spectroscopy during recent years. Among the wide range of optical techniques available, we chose these three for this review because they have the ability to provide biochemical information and show great potential for real-time deep-tissue point-based in vivo analysis. This review also highlights the importance of saliva-based potential biomarkers for non-invasive early-stage diagnosis. It concludes with the discussion on the scope of development and future demands from a clinical point of view.

Insights into Biochemical Sources and Diffuse Reflectance Spectral Features for Colorectal Cancer Detection and Localization.

Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide. Early detection not only reduces mortality but also improves patient prognosis by allowing the use of minimally invasive techniques to remove cancer while avoiding major surgery. Expanding the use of microsurgical techniques requires accurate diagnosis and delineation of the tumor margins in order to allow complete excision of cancer. We have used diffuse reflectance spectroscopy (DRS) to identify the main optical CRC biomarkers and to optimize parameters for the integration of such technologies into medical devices. A total number of 2889 diffuse reflectance spectra were collected in ex vivo specimens from 47 patients. Short source-detector distance (SDD) and long-SDD fiber-optic probes were employed to measure tissue layers from 0.5 to 1 mm and from 0.5 to 1.9 mm deep, respectively. The most important biomolecules contributing to differentiating DRS between tissue types were oxy- and deoxy-hemoglobin (Hb and HbO2), followed by water and lipid. Accurate tissue classification and potential DRS device miniaturization using Hb, HbO2, lipid and water data were achieved particularly well within the wavelength ranges 350-590 nm and 600-1230 nm for the short-SDD probe, and 380-400 nm, 420-610 nm, and 650-950 nm for the long-SDD probe.

Silicon Photomultiplier-A High Dynamic Range, High Sensitivity Sensor for Bio-Photonics Applications.

This work is an overview of silicon photomultipliers (SiPMs) with a view to defining their importance for bio-photonic and clinical applications. SiPMs are benchmarked against other common photodetectors, namely, PIN diodes and avalanche photodetectors (APDs) and are compared with respect to important circuit design parameters. It will be shown that careful selection of the design bias voltage, overvoltage, gain defining components and device integration to micro-optics can allow SiPM detectors to achieve considerable sensitivity for auto-fluorescence (AF) detection and a wide dynamic range at low optical powers (~1 pW to ~4 µW). The SiPM has a manageable bias voltage (~25 V to ~30 V DC) for systems integration, and with optimised sensitivity it will enhance bio-photonic research in the area of AF to detect intraoperatively, for example, brain tumour margins.

Gas in scattering media absorption spectroscopy as a potential tool in neonatal respiratory care.

Gas in scattering media absorption spectroscopy (GASMAS) is a novel optical technology employing near-infrared light. It has a potential use in the medical setting as a monitoring and diagnostic tool by detecting molecular oxygen within gas pockets and thus may be a useful adjunct in respiratory monitoring. GASMAS has potential advantages over other monitoring devices currently used in clinical practice. It is a non-invasive, continuous, non-ionising technology and provides unique information about molecular oxygen content inside the lungs. GASMAS may have a future role in optimising respiratory management of neonates in different clinical scenarios such as monitoring cardiorespiratory transition in the delivery room, assessing surfactant deficiency, and optimising endotracheal tube positioning. This article aims to summarise current evidence exploring GASMAS application in a neonate, discuss possible clinical benefits, and compare with other devices that are currently used in neonatal care. IMPACT: This article presents a novel optical technique to measure lung oxygen concentrations that may have important clinical uses. This review summarises the current literature investigating the concept of optical lung oxygen measurement. Information from this review can guide researchers in future studies.

Perspective on the integration of optical sensing into orthopedic surgical devices.

SIGNIFICANCE: Orthopedic surgery currently comprises over 1.5 million cases annually in the United States alone and is growing rapidly with aging populations. Emerging optical sensing techniques promise fewer side effects with new, more effective approaches aimed at improving patient outcomes following orthopedic surgery. AIM: The aim of this perspective paper is to outline potential applications where fiberoptic-based approaches can complement ongoing development of minimally invasive surgical procedures for use in orthopedic applications. APPROACH: Several procedures involving orthopedic and spinal surgery, along with the clinical challenge associated with each, are considered. The current and potential applications of optical sensing within these procedures are discussed and future opportunities, challenges, and competing technologies are presented for each surgical application. RESULTS: Strong research efforts involving sensor miniaturization and integration of optics into existing surgical devices, including K-wires and cranial perforators, provided the impetus for this perspective analysis. These advances have made it possible to envision a next-generation set of devices that can be rigorously evaluated in controlled clinical trials to become routine tools for orthopedic surgery. CONCLUSIONS: Integration of optical devices into surgical drills and burrs to discern bone/tissue interfaces could be used to reduce complication rates across a spectrum of orthopedic surgery procedures or to aid less-experienced surgeons in complex techniques, such as laminoplasty or osteotomy. These developments present both opportunities and challenges for the biomedical optics community.

Lung tissue phantom mimicking pulmonary optical properties, relative humidity, and temperature: a tool to analyze the changes in oxygen gas absorption for different inflated volumes.

SIGNIFICANCE: Gas in scattering media absorption spectroscopy (GASMAS) enables noninvasive gas sensing in the body. It is developing as a tool for diagnosis and monitoring of respiratory conditions in neonates. Phantom models with relevant features to the clinical translation of GASMAS technology are necessary to understand technical challenges and potential applications of this technique. State-of-the-art phantoms designed for this purpose have focused on the optical properties and anthropomorphic geometry of the thorax, contributing to the source-detector placement, design, and optimization. Lung phantom mimicking the alveolar anatomy has not been included in the existent models due to the inherent complexity of the tissue. We present a simplified model that recreates inflated alveoli embedded in lung phantom. AIM: The goal of this study was to build a lung model with air-filled structures mimicking inflated alveoli surrounded by optical phantom with accurate optical properties (µa = 0.50 cm - 1 and µs'=5.4 cm-1) and physiological parameters [37°C and 100% relative humidity (RH)], and to control the air volume within the phantom to demonstrate the feasibility of GASMAS in sensing changes in pulmonary air volume. APPROACH: The lung model was built using a capillary structure with analogous size to alveolar units. Part of the capillaries were filled with liquid lung optical phantom to recreate scattering and absorption, whereas empty capillaries mimicked air filled alveoli. The capillary array was placed inside a custom-made chamber that maintained pulmonary temperature and RH. The geometry of the chamber permitted the placement of the laser head and detector of a GASMAS bench top system (MicroLab Dual O2 / H2O), to test the changes in volume of the lung model in transmittance geometry. RESULTS: The lung tissue model with air volume range from 6.89 × 10 - 7 m3 to 1.80 × 10 - 3 m3 was built. Two measurement sets, with 10 different capillary configurations each, were arranged to increase or decrease progressively (in steps of 3.93 × 10 - 8 m3) the air volume in the lung model. The respective GASMAS data acquisition was performed for both data sets. The maximum absorption signal was obtained for configurations with the highest number of air-filled capillaries and decreased progressively when the air spaces were replaced by capillaries filled with liquid optical phantom. Further studies are necessary to define the minimum and maximum volume of air that can be measured with GASMAS-based devices for different source-detector geometries. CONCLUSIONS: The optical properties and the structure of tissue from the respiratory zone have been modeled using a simplified capillary array immersed in a controlled environment chamber at pulmonary temperature and RH. The feasibility of measuring volume changes with GASMAS technique has been proven, stating a new possible application of GASMAS technology in respiratory treatment and diagnostics.

Perspectives on interstitial photodynamic therapy for malignant tumors.

SIGNIFICANCE: Despite remarkable advances in the core modalities used in combating cancer, malignant diseases remain the second largest cause of death globally. Interstitial photodynamic therapy (IPDT) has emerged as an alternative approach for the treatment of solid tumors. AIM: The aim of our study is to outline the advancements in IPDT in recent years and provide our vision for the inclusion of IPDT in standard-of-care (SoC) treatment guidelines of specific malignant diseases. APPROACH: First, the SoC treatment for solid tumors is described, and the attractive properties of IPDT are presented. Second, the application of IPDT for selected types of tumors is discussed. Finally, future opportunities are considered. RESULTS: Strong research efforts in academic, clinical, and industrial settings have led to significant improvements in the current implementation of IPDT, and these studies have demonstrated the unique advantages of this modality for the treatment of solid tumors. It is envisioned that further randomized prospective clinical trials and treatment optimization will enable a wide acceptance of IPDT in the clinical community and inclusion in SoC guidelines for well-defined clinical indications. CONCLUSIONS: The minimally invasive nature of this treatment modality combined with the relatively mild side effects makes IPDT a compelling alternative option for treatment in a number of clinical applications. The adaptability of this technique provides many opportunities to both optimize and personalize the treatment.

Combined autofluorescence and diffuse reflectance for brain tumour surgical guidance: initial ex vivo study results.

This ex vivo study was conducted to assess the potential of using a fibre optic probe system based on autofluorescence and diffuse reflectance for tissue differentiation in the brain. A total of 180 optical measurements were acquired from 28 brain specimens (five patients) with eight excitation and emission wavelengths spanning from 300 to 700 nm. Partial least square-linear discriminant analysis (PLS-LDA) was used for tissue discrimination. Leave-one-out cross validation (LOOCV) was then used to evaluate the performance of the classification model. Grey matter was differentiated from tumour tissue with sensitivity of 89.3% and specificity of 92.5%. The variable importance in projection (VIP) derived from the PLS regression was applied to wavelengths selection, and identified the biochemical sources of the detected signals. The initial results of the study were promising and point the way towards a cost-effective, miniaturized hand-held probe for real time and label-free surgical guidance.

Evaluation of wavelength ranges and tissue depth probed by diffuse reflectance spectroscopy for colorectal cancer detection.

Colorectal cancer (CRC) is the third most common type of cancer worldwide and the second most deadly. Recent research efforts have focused on developing non-invasive techniques for CRC detection. In this study, we evaluated the diagnostic capabilities of diffuse reflectance spectroscopy (DRS) for CRC detection by building 6 classification models based on support vector machines (SVMs). Our dataset consists of 2889 diffuse reflectance spectra collected from freshly excised ex vivo tissues of 47 patients over wavelengths ranging from 350 and 1919 nm with source-detector distances of 630-µm and 2500-µm to probe different depths. Quadratic SVMs were used and performance was evaluated using twofold cross-validation on 10 iterations of randomized training and test sets. We achieved (93.5 ± 2.4)% sensitivity, (94.0 ± 1.7)% specificity AUC by probing the superficial colorectal tissue and (96.1 ± 1.8)% sensitivity, (95.7 ± 0.6)% specificity AUC by sampling deeper tissue layers. To the best of our knowledge, this is the first DRS study to investigate the potential of probing deeper tissue layers using larger SDD probes for CRC detection in the luminal wall. The data analysis showed that using a broader spectrum and longer near-infrared wavelengths can improve the diagnostic accuracy of CRC as well as probing deeper tissue layers.

Photodynamic therapy dosimetry using multiexcitation multiemission wavelength: toward real-time prediction of treatment outcome.

Evaluating the optical properties of biological tissues is needed to achieve accurate dosimetry during photodynamic therapy (PDT). Currently, accurate assessment of the photosensitizer (PS) concentration by fluorescence measurements during PDT is typically hindered by the lack of information about tissue optical properties. In the present work, a hand-held fiber-optic probe instrument monitoring fluorescence and reflectance is used for assessing blood volume, reduced scattering coefficient, and PS concentration facilitating accurate dosimetry for PDT. System validation was carried out on tissue phantoms using nonlinear least squares support machine regression analysis. It showed a high correlation coefficient (>0.99) in the prediction of the PS concentration upon a large variety of phantom optical properties. In vivo measurements were conducted in a PDT chlorine e6 dose escalating trial involving 36 male Swiss mice with Ehrlich solid tumors in which fluences of 5, 15, and 40 J cm - 2 were delivered at two fluence rates (100 and 40 mW cm - 2). Remarkably, quantitative measurement of fluorophore concentration was achieved in the in vivo experiment. Diffuse reflectance spectroscopy (DRS) system was also used to independently measure the physiological properties of the target tissues for result comparisons. Then, blood volume and scattering coefficient measured by the fiber-optic probe system were compared with the corresponding result measured by DRS and showed agreement. Additionally, tumor hemoglobin oxygen saturation was measured using the DRS system. Overall, the system is capable of assessing the implicit photodynamic dose to predict the PDT outcome.

Emerging applications of upconverting nanoparticles in intestinal infection and colorectal cancer.

Colorectal cancer is the abnormal growth of cells in colon or rectum. Recent findings have acknowledged the role of bacterial infection and chronic inflammation in colorectal cancer initiation and progression. In order to detect and treat precancerous lesions, new tools are required, which may help to prevent or identify colorectal cancer at an early stage. To date, several different screening tests are available, including endoscopy, stool-based blood tests, and radiology-based tests. However, these analyses either lack sensitivity or are of an invasive nature. The use of fluorescently labeled probes can increase the detection sensitivity. However, autofluorescence, photobleaching, and photodamage are commonly encountered problems with fluorescence imaging. Upconverting nanoparticles (UCNPs) are recently developed lanthanide-doped nanocrystals that can be used as light-triggered luminescent probes and in drug delivery systems. In this review, we comprehensively summarize the recent developments and address future prospects of UCNP-based applications for diagnostics and therapeutic approaches associated with intestinal infection and colorectal cancer.

Computer simulation analysis of source-detector position for percutaneously measured O2 -gas signal in a three-dimensional preterm infant lung.

Further improvements in the clinical care of our most vulnerable patients-preterm infants-are needed. Novel diagnostic and surveillance tools facilitate such advances. The GASMAS technique has shown potential to become a tool to, noninvasively, monitor gas in the lungs of preterm infants, by placing a laser source and a detector on the chest wall skin. It is believed that this technology will become a valuable clinical diagnostic tool for monitoring the lung function of these patients. Today, the technology is, for this application, in an early stage and further investigations are needed. In the present study, a three-dimensional computer model of the thorax of an infant is constructed, from a set of CT images. Light transport simulations are performed to provide information about the position dependence of the laser- and detector probe on the thorax of the infant. The result of the simulations, based on the study method and the specified model used in this work, indicates that measurement geometries in front and on the side of the lung are favorable in order to obtain a good gas absorption signal.