Gas Monitoring in Human Frontal Sinuses-Stability Considerations and Gas Exchange Studies.

Acute rhinosinusitis is a common infectious disease, which, in more than 90% of cases, is caused by viruses rather than by bacteria. Even so, antibiotics are often unnecessarily prescribed, and in the long run this contributes to the alarming level of antibiotics resistance. The reason is that there are no good guiding tools for defining the background reason of the infection. One main factor for the clearance of the infection is if there is non-obstructed ventilation from the sinus to the nasal cavity. Gas in Scattering Media Absorption Spectroscopy (GASMAS) has potential for diagnosing this. We have performed a study of frontal sinuses of volunteers with a focus on signal stability and reproducibility over time, accurate oxygen concentration determination, and assessment of gas transport through passages, naturally and after decongestant spray administration. Different from earlier studies on frontal sinuses, water vapor, serving the purpose of oxygen signal normalization, was measured at 818 nm rather than earlier at 937 nm, now closer to the 760 nm oxygen absorption band and thus resulting in more reliable results. In addition, the action of decongestants was objectively demonstrated for the first time. Evaluated oxygen concentration values for left- and right-hand side sinus cavities were found to agree within 0.3%, and a left-right geometrical asymmetry parameter related to anatomical differences was stable within 10%.

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.

Ripening of avocado fruits studied by spectroscopic techniques.

Avocados are considered very healthy due to the high content mono-unsaturated lipid, essential vitamins and minerals, minimal sugar and no cholesterol and are therefore sometimes referred to as "the perfect fruits". Avocados, mainly grown in Latin-America, are harvested unripe and sent overseas. However, the ripening process is very difficult to assess visually and tactilely. A tool for precise noninvasive judgment of the status would be valuable as the fruit is too expensive to be cut open unripe or overdue. A white-light source and a light-emitting diode unit with four excitation wavelengths (365, 385, 395, and 405 nm) were used for reflectance and fluorescence spectroscopy in a fiber-coupled set-up for noninvasive monitoring. Twelve non-ripe avocados, with approximately the same size and appearance, were studied and divided into three groups and kept at three different storage conditions; at room temperature, in a refrigerator and a combination of the two. We showed that fluorescence was useful for following the ripening process. A method, which compensates for the spatial variations in spectral properties around a fruit, is described. Remote fluorescence monitoring, intended for orchard use, was also demonstrated. A low-cost device based on fluorescence for avocado ripeness assessment is proposed.

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.

Laser-based gas absorption spectroscopy in decaying hip bone: water vapor as a predictor of osteonecrosis.

Affluent blood flow through a complicated net of vessels supplies skeletal bone tissue with oxygen and nutrients. Due to accidental events or physiological processes, the blood supply might be deficient or even disrupted, and the healthy bone decays in a process that, for the hip location, is denoted as osteonecrosis of the femoral head (ONFH) or avascular femoral head necrosis. Early diagnosis is important for the prognosis. X-ray-based imaging, such as CT or MRI, is not of much value for the early detection. As the decay theoretically is associated with the development of gas-filled pores, gas analysis should have diagnostic value. We have introduced gas in scattering media absorption spectroscopy, as a complementary modality. Eighteen extracted femoral joint heads, diseased as well as normal, were investigated. Diseased samples are associated with clear signals due to water vapor, whereas the normal ones largely lack such features. The results suggest that free water vapor could serve as an early indicator of pore development and thus as a promising predictor of ONFH pathological changes, once the technique has been fully refined.

Non-intrusive studies of gas contents and gas diffusion in hen eggs.

A detailed study of the condition of eggs was performed using tunable diode lasers to monitor free gas in hen eggs. We detected oxygen and water vapor signals from 13 unfertilized eggs and studied the growth of the egg air cell over a time period of 3 weeks. We also studied the gas exchange through the egg shell, which is of particular interest for fertilized eggs. Four fertilized and five unfertilized eggs were followed over 3 weeks, the hatching period for hen eggs, and significant variations were found both in time and for the two types of eggs. Our results indicate that the techniques could be developed for automatic control of egg freshness, as well as for monitoring the hatching progress of fertilized eggs.

Towards an optical diagnostic system for otitis media using a combination of otoscopy and spectroscopy.

An improved method, where conventional otoscope investigation of human suspicious otitis media is combined with diffuse reflectance spectroscopy and gas in scattering media absorption spectroscopy (GASMAS) is being developed. Otitis media is one of the most common infectious diseases in children, whose Eustachian tube connecting the middle ear with the nasal cavity is more horizontal than for adults, which leads to impaired fluid drainage. At present, the use of an otoscope to visually observe possible changes in the tympanic membrane appearance is the main diagnostics method for otitis media. Inaccurate diagnosis related to similar symptoms, and the difficulty for small children to describe the condition experienced, frequently leads to over-prescription of antibiotics and alarming increase in bacterial resistance development. More accurate diagnostic methods are highly desirable. Diffuse reflectance spectroscopy is a non-invasive quantitative spectroscopic technique that enables to objectively quantify changes in the hemoglobin content of the tympanic membrane related to inflammation. If an infection is present, the ventilatory function of the Eustachian tube is frequently impaired and the middle-ear cavity will be filled with fluid. GASMAS, a non-invasive detection method, can non-invasively determine if gas is replaced by fluid in the middle-ear cavity.

The bat-bird-bug battle: daily flight activity of insects and their predators over a rice field revealed by high-resolution Scheimpflug Lidar.

We present the results of, to our knowledge, the first Lidar study applied to continuous and simultaneous monitoring of aerial insects, bats and birds. It illustrates how common patterns of flight activity, e.g. insect swarming around twilight, depend on predation risk and other constraints acting on the faunal components. Flight activity was monitored over a rice field in China during one week in July 2016, using a high-resolution Scheimpflug Lidar system. The monitored Lidar transect was about 520 m long and covered approximately 2.5 m3. The observed biomass spectrum was bimodal, and targets were separated into insects and vertebrates in a categorization supported by visual observations. Peak flight activity occurred at dusk and dawn, with a 37 min time difference between the bat and insect peaks. Hence, bats started to feed in declining insect activity after dusk and stopped before the rise in activity before dawn. A similar time difference between insects and birds may have occurred, but it was not obvious, perhaps because birds were relatively scarce. Our observations are consistent with the hypothesis that flight activity of bats is constrained by predation in bright light, and that crepuscular insects exploit this constraint by swarming near to sunset/sunrise to minimize predation from bats.

Detection of free oxygen and water vapor in fertilized and unfertilized eggs by diode laser spectroscopy-Exploration of diagnostics possibilities.

Nonintrusive methods for characterizing food products are of increasing interest related to the greater awareness of food safety issues. Hen eggs are an important part in food consumption in most parts of the world. We have investigated an optical method utilizing tunable diode lasers for monitoring free gas in eggs. We show that oxygen signals, recorded around 760 nm, increase steadily as eggs become older. Further, we investigated fertilized eggs, which show a quite different temporal behavior during the hatching time. The oxygen signal decreases here with time, while water vapor, recorded around 937 nm, shows a steady increase. Conclusions regarding the size of the air cell and the oxygen availability in fertilized eggs are drawn. The technique might be developed for automatic control of egg freshness, as well as for assessing if eggs are fertilized or not.

Application of Tunable Diode Laser Spectroscopy for the Assessment of Food Quality.

Adequate food packaging is important to ensure food quality and prolong the shelf life of food. Frequently, the method of modified atmosphere packaging (MAP) is used. We used a tunable diode laser spectroscopy technique to detect the oxygen content in food packages, e.g., in packaged milk and bread. Different detection geometries were adopted to be able to collect scattering light that had passed through the gas volume in the packages, and to avoid the disturbance of ambient air. Furthermore, studies of the bread-baking process have been performed by measuring the water vapor signals in a fermenting dough. The results demonstrate that the technique has a great potential for nonintrusive assessment of food quality and the bread-baking process.

Diagnostics of femoral head status in humans using laser spectroscopy - In vitro studies.

Osteonecrosis of the femoral head (ONFH), a recalcitrant and disabling disease, is caused by inadequate or fully disrupted blood supply to the affected segment of the subchondral bone. Theoretically, there will develop gas-filled pores during the bone decay process due to lacking blood supply. Unfortunately, the relationship between the gas-filled pores and ONFH is still unclear. Here, we have introduced diode laser absorption spectroscopy to detect oxygen and water vapor signals in the femoral heads from hip replacement in 19 patients. Five samples are affected by osteoarthritis (OA) and the others are related to ONFH. Oxygen and water vapor signals could be obtained, demonstrating the presence of gas-filled pores in both the OA and ONFH groups while the measurement results showed no significant difference. A study of gas exchange was also performed on one excised bone sample to study how these gas pores communicate with the ambient air. The results suggested that the obtained oxygen signals inside the bone samples originate from the invasion of ambient air, which is not expected in vivo. In conclusion, the ability to detect the gas signal of laser absorption spectroscopy shows the potential for the medical application of assessing the human femoral head in vivo.

Gas exchange in fruits related to skin condition and fruit ripening studied with diode laser spectroscopy.

The concentration of the biologically active molecular oxygen gas is of crucial importance for fruits in the metabolic respiration, maturation, and ripening processes. In our study, oxygen content and oxygen transport in fruits, exemplified by apples and guavas, were studied noninvasively by gas in scattering media absorption spectroscopy. The technique is based on the fact that free gases typically have 10,000 times narrower absorption features than the bulk material. The technique was demonstrated in studies of the influence of the fruit skin in regulating the internal oxygen balance, by observing the signal response of the internal oxygen gas to a transient change in the ambient gas concentration on peeled and unpeeled fruits. In addition, the gas exchange rate at different ripening stages was also studied in intact guavas.

Laser spectroscopy applied to environmental, ecological, food safety, and biomedical research.

Laser spectroscopy provides many possibilities for multi-disciplinary applications in environmental monitoring, in the ecological field, for food safety investigations, and in biomedicine. The paper gives several examples of the power of multi-disciplinary applications of laser spectroscopy as pursued in our research group. The studies utilize mostly similar and widely applicable spectroscopic approaches. Air pollution and vegetation monitoring by lidar techniques, as well as agricultural pest insect monitoring and classification by elastic scattering and fluorescence spectroscopy are described. Biomedical aspects include food safety applications and medical diagnostics of sinusitis and otitis, with strong connection to the abatement of antibiotics resistance development.

Diode laser spectroscopy for noninvasive monitoring of oxygen in the lungs of newborn infants.

BACKGROUND: Newborn infants may have pulmonary disorders with abnormal gas distribution, e.g., respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel noninvasive optical technique for rapid nonradiographic bedside detection of oxygen gas in the lungs of full-term newborn infants. METHODS: Laser spectroscopy was used to measure contents of oxygen gas (at 760 nm) and of water vapor (at 937 nm) in the lungs of 29 healthy newborn full-term infants (birth weight 2,900-3,900 g). The skin above the lungs was illuminated using two low-power diode lasers and diffusely emerging light was detected with a photodiode. RESULTS: Of the total 390 lung measurements performed, clear detection of oxygen gas was recorded in 60%, defined by a signal-to-noise ratio of >3. In all the 29 infants, oxygen was detected. Probe and detector positions for optimal pulmonary gas detection were determined. There were no differences in signal quality with respect to gender, body side or body weight. CONCLUSION: The ability to measure pulmonary oxygen content in healthy full-term neonates with this technique suggests that with further development, the method might be implemented in clinical practice for lung monitoring in neonatal intensive care.

Optical detection of middle ear infection using spectroscopic techniques: phantom experiments.

A noninvasive optical technique, which is based on a combination of reflectance spectroscopy and gas in scattering media absorption spectroscopy, is demonstrated. It has the potential to improve diagnostics of middle ear infections. An ear phantom prepared with a tissue cavity, which was covered with scattering material, was used for spectroscopic measurements. Diffuse reflectance spectra of the phantom eardrum were measured with a reflectance probe. The presence of oxygen and water vapor as well as gas exchange in the phantom cavity were studied with a specially designed fiber-optic probe for backscattering detection geometry. The results suggest that this method can be developed for improved clinical detection of middle ear infection.

Assessment of human sinus cavity air volume using tunable diode laser spectroscopy, with application to sinusitis diagnostics.

Sinusitis is a very common disease and improved diagnostic tools are desirable also in view of reducing over-prescription of antibiotics. A non-intrusive optical technique called GASMAS (GAs in Scattering Media Absorption Spectroscopy), which has a true potential of being developed into an important complement to other means of detection, was utilized in this work. Water vapor in the frontal sinuses, related to the free gas volume, was studied at around 937 nm in healthy volunteers. The results show a good stability of the GASMAS signals over extended times for the frontal sinuses for all volunteers, showing promising applicability to detect anomalies due to sinusitis. Measurements were also performed following the application of a decongestion spray. No noticeable signal change was observed, which is consistent with the fact that the water vapor concentration is given by the temperature only, and is not influenced by changes in cavity ventilation. Evaluated GASMAS data recorded on 6 consecutive days show signal stability for the left and right frontal sinus in one of the test volunteers.

Pharmacokinetic and biodistribution study following systemic administration of Fospeg®--a Pegylated liposomal mTHPC formulation in a murine model.

Fospeg® is a newly developed photosensitizer formulation based on meso-tetra(hydroxyphenyl)chlorin (mTHPC), with hydrophilic liposomes to carry the hydrophobic photosensitizer to the target tissue. In this study the pharmacokinetics and biodistribution of Fospeg® were investigated by high performance liquid chromatography at various times (0.5-18 hours) following systemic i.v. administration. As a model an experimental HT29 colon tumor in NMRI nu/nu mice was employed. Our study indicates a higher plasma peak concentration, a longer circulation time and a better tumor-to-skin ratio than those of Foslip®, another liposomal mTHPC formulation. Data from ex vivo tissue fluorescence and reflectance imaging exhibit good correlation with chemical extraction. Our results have shown that optical imaging provides the potential for fluorophore quantification in biological tissues.

Studies of tropical fruit ripening using three different spectroscopic techniques.

We present a noninvasive method to study fruit ripening. The method is based on the combination of reflectance and fluorescence spectroscopies, as well as gas in scattering media absorption spectroscopy (GASMAS). Chlorophyll and oxygen are two of the most important constituents in the fruit ripening process. Reflectance and fluorescence spectroscopies were used to quantify the changes of chlorophyll and other chromophores. GASMAS, based on tunable diode laser absorption spectroscopy, was used to measure free molecular oxygen in the fruit tissue at 760 nm, based on the fact that the free gases have much narrower spectral imprints than those of solid materials. The fruit maturation and ripening processes can be followed by studying the changes of chlorophyll and oxygen contents with these three techniques.

Noninvasive monitoring of gas in the lungs and intestines of newborn infants using diode lasers: feasibility study.

Preterm newborn infants have a high morbidity rate. The most frequently affected organs where free gas is involved are the lungs and intestines. In respiratory distress syndrome, both hyperexpanded and atelectatic (collapsed) areas occur, and in necrotizing enterocolitis, intramural gas may appear in the intestine. Today, these conditions are diagnosed with x-ray radiography. A bed-side, rapid, nonintrusive, and gas-specific technique for in vivo gas sensing would improve diagnosis. We report the use of noninvasive laser spectroscopy, for the first time, to assess gas content in the lungs and intestines of three full-term infants. Water vapor and oxygen were studied with two low-power diode lasers, illuminating the skin and detecting light a few centimeters away. Water vapor was easily detected in the intestines and was also observed in the lungs. The relatively thick chest walls of the infants prevented detection of the weaker oxygen signal in this study. However, results from a previous phantom study, together with scaling of the results presented here to the typical chest-wall thickness of preterm infants, suggest that oxygen also should be detectable in their lungs.