Translation of Gas Spectroscopy into the Clinic, a Promising Tool for Non-Invasive Diagnostics in Respiratory Health Care of Neonates

Respiratory Distress Syndrome (RDS) is the leading cause of death among preterm infants worldwide. The latest improvements made in tackling RDS are focused on less invasive surfactant therapy and non-invasive ventilation. As a consequence of the more advanced and intensive respiratory support, there is an increase in the prevalence of infants with chronic lung disease. The current first line techniques used to monitor at risk infants with respiratory distress are pulse oximetry, chest radiography (X-ray) and blood gas analysis with X-ray imaging being the main diagnostic tool used. However, ionized radiation can be harmful for the infant and exposure should be kept to the minimum requirement. Translation of the gas spectroscopy to the clinic could provide additional information about alveolar composition and make the step forward in objective medical assessment for RDS in neonates. Lack of direct, non-invasive method of measuring the oxygen concentration in the lung instead of oxygen saturation in blood, precludes understanding of underlying cause of the RDS and real time monitoring of the response of neonates under treatment. Gas spectroscopy has proven successful in quantifying gas content inside cavities surrounded by solids or liquids, and thus may be used to assess the oxygen content in the lungs of a neonate. This non-invasive light-based technology opens a new range of tools for lung function assessment, as it can be used to map continuously the oxygen presence and the changes in the volume of the lungs during respiration. Its superior specificity makes it a good candidate for the early diagnosis of respiratory distress. In addition, it could also be integrated to existing equipment to help optimize respiratory support during treatment.

Although current research is aiming for less invasive and more targeted diagnostics and treatment techniques [6], the main tool is X-ray imaging such as chest radiograph or rarely volumetric computed tomography (CT) with the drawback of radiation burden [7]. Alternative non harmful diagnostic tools are magnetic resonance imaging (MRI) and ultrasound imaging. The image quality of MRI can be affected by heartbeat and respiration motion and there is still on-going work to fully achieve lung imaging comparable to CT [8]. Lung ultrasound imaging has been proven to be of good use for bedside differential diagnosis of RDS in new-borns [9,10].
While the above-mentioned imaging techniques enable the localization of gas filled cavities in the body, none of them make it possible for the quantification of alveolar gas composition in real time. Gas in Scattering Media Absorption Spectroscopy (GASMAS) is a non-invasive optical technique which can be used to measure continuously oxygen concentration and inflated volume locally in the lung [11]. The clinical applications of this novel technology are currently being explored and this article provides insights into the potential improvements that could rise from translating GASMAS as a rapid non-radiographic bedside detection of alveolar oxygen gas for neonatal respiratory health care.

Principles of GASMAS technique
Optical spectroscopy is widely used to provide information on different gas species [12]. GASMAS refers to the regime where the absorbing gas is inside a highly scattering media and relies on the difference between the absorptive imprints between solid-state materials and free gas. The absorption spectrum of free oxygen inside the alveoli is 10,000 times narrower than those of blood, and other surrounding tissues of the thoracic cavity. The deepest penetration of light in human tissue corresponds to wavelengths between 650 nm and 1.4 microns. Since molecular oxygen has a wide range of absorption lines around 760 nm and water vapor has numerous lines around 820 and 980 nm, the selection of light sources for clinical applications of GASMAS in respiratory health care are restricted to these wavelengths [13].
Previous feasibility studies demonstrated that gas sensing in the lung can be achieved by sending low-intensity laser light through the thoracic wall and detecting the emerging light with a photodetector, which reveals the absorption imprints of oxygen and water vapor [14]. The Beer-Lambert law is used to assess the gas concentration. In scattering media, the path length is not well defined; hence two wavelengths are necessary to tune across the absorption lines of water vapor and molecular oxygen simultaneously. By making the assumption that optical properties are the same for the two wavelengths, the absorption signal from oxygen is normalized by the water vapor one and then the absolute concentration of oxygen is calculated [15].

Potential clinical application of GASMAS
In the transition from intrauterine environment to air, immediately after birth, the neonate fills the airways down to the alveolar level with air to start breathing and gas exchange. Preterm  [17]. Inflammation is an indication that CLD will develop. GASMAS technology is also capable of measuring inflated volume in the lung and can potentially quantify inflammatory changes within the lungs of preterm infants. This would present a huge step in the optimization of clinical care, since chest radiography, the gold standard for diagnosis, might not always correlate with the clinical severity in CLD [7]. Postnatal infections, including sepsis and pneumonia are also risk factors for CLD where lung injury is thought to be mediated by inflammation [18]. Further studies could determine if infection of lung tissue has a gaseous biological marker. If so, GASMAS technology could optimize antibiotics administration.
to achieve a thorough lung function assessment of new-borns and help in the diagnosis of underlying respiratory conditions, diminishing the need of X-ray imaging. GASMAS technology may have a very important role to play in optimizing respiratory support for preterm infants and potentially decrease the incidence of CLD.