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Adequate oxygenation is essential for normal embryogenesis and fetal growth. Perturbations in the intrauterine oxidative environment during pregnancy are associated with several pathophysiological disorders such as pregnancy loss, preeclampsia, and intrauterine growth restriction. We proposed to use optoacoustic technology for monitoring placental and fetal umbilical blood oxygenation. In this work, we studied optoacoustic monitoring of oxygenation in placenta and umbilical cord blood ex vivo using technique of placenta perfusion. We used a medical grade, nearinfrared, tunable, optoacoustic system developed and built for oxygenation monitoring in blood vessels and in tissues. First, we calibrated the system for cord blood oxygenation measurements by using a CO-Oximeter (gold standard). Then we performed validation in cord blood circulating through the catheters localized on the fetal side of an isolated placental lobule. Finally, the oxygenation measurements were performed in the perfused placental tissue. To increase or decrease blood oxygenation, we used infusion of a gas mixture of 95% O 2 + 5% CO 2 and 95% N 2 + 5% CO 2 , respectively. In placental tissue, up to four cycles of changes in oxygenation were performed. The optoacoustically measured oxygenation in circulating cord blood and in placental lobule closely correlated with the actual oxygenation data measured by CO-Oximeter. We plan to further test the placental and cord blood oxygenation monitoring with optoacoustics in animal and clinical studies.

Premature, very-low-birth-weight (VLBW; ≤1500 g) and low-birth-weight (LBW; 1500-2499 g) infants are at increased risk for severe neurological disability. 25-50% of the 63,000 VLBW infants born annually in the USA have major longterm cognitive or neurobehavioral deficits in which cerebral hypoxia plays an important role. At present, no technology is capable of noninvasive, accurate monitoring of cerebral oxygenation in newborns. We proposed to use an optoacoustic technique for noninvasive cerebral hypoxia monitoring by probing the superior sagittal sinus (SSS). Recently, we developed and built a medical grade, multi-wavelength, near-infrared optoacoustic system suitable for neonatal applications. We designed and built an adjustable patient interface for neonates with VLBW, LBW, and normal weight (NBW) that provides single or continuous measurements of the SSS blood oxygenation in both the reflection and transmission modes. We performed pilot clinical tests of the system in VLBW, LBW, and NBW hemodynamically stable infants admitted to the neonatal intensive care unit. The system was capable of detecting SSS signals through the open anterior and posterior fontanelles and through the skull and allowed for monitoring of the SSS blood oxygenation in both modes. To the best of our knowledge this paper reports for the first time detection of optoacoustic signals from human cerebral blood vessels in both the transmission mode and the reflection mode. Analysis of the signals allows for noninvasive measurement of cerebral venous blood oxygenation in newborns in both modes. The transmission mode can be used for accurate measurement of the total hemoglobin concentration as well. The method and system proposed in this study can be used for optoacoustic human brain imaging, tomography, and mapping.

Early diagnosis of intracranial hematomas is necessary to improve outcome in patients with traumatic brain injury (TBI). CT and MRI can diagnose intracranial hematomas, but cannot be used until the patient arrives at a major healthcare facility, resulting in delayed diagnosis. Near infrared spectroscopy may suggest the presence of unilateral intracranial hematomas, but provides minimal information on hematoma type and location due to limitations associated with strong light scattering. We have used optoacoustics (which combines high endogenous optical contrast with the resolution of ultrasound) to diagnose hematomas and monitor cerebral oxygenation. We performed animal and clinical studies on detection and characterization of hematomas and on monitoring cerebral hypoxia by probing the superior sagittal sinus (SSS). Recently, we built a medical grade, multi-wavelength, OPO-based optoacoustic system tunable in the near infrared spectral range. We developed new patient interfaces for noninvasive, transcranial measurements in the transmission mode in the presence of dense hair and used it in patients with TBI. The optoacoustic system was capable of detecting and characterizing intra- and extracranial hematomas. SSS blood oxygenation was measured as well with the new interface. The obtained results indicate that the optoacoustic system in the transmission mode provides detection and characterization of hematomas in TBI patients, as well as cerebral venous blood oxygenation monitoring. The transmission mode approach can be used for optoacoustic brain imaging, tomography, and mapping in humans. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Patients with acute intracranial hematomas often require surgical drainage within the first four hours after traumatic brain injury (TBI) to avoid death or severe neurologic disability. CT and MRI permit rapid, noninvasive diagnosis of hematomas, but can be used only at a major health-care facility. At present, there is no device for noninvasive detection and characterization of hematomas in pre-hospital settings. We proposed to use an optoacoustic technique for rapid, noninvasive diagnosis and monitoring of hematomas, including intracranial hematomas. Unlike bulky CT and MR equipment, an optoacoustic system can be small and easily transported in an emergency vehicle. In this study we used a specially-designed blast device to inflict TBI in rats. A near-infrared OPO-based optoacoustic system developed for hematoma diagnosis and for blood oxygenation monitoring in the superior sagittal sinus (SSS) in small animals was used in the study. Optoacoustic signals recorded simultaneously from the SSS and hematomas allowed for measurements of their oxygenations. The presence of hematomas was confirmed after the experiment in gross pictures of the exposed brains. After blast the hematoma signal and oxygenation increased, while SSS oxygenation decreased due to the blastinduced TBI. The increase of the oxygenation in fresh hematomas may be explained by the leakage of blood from arteries which have higher blood pressure compared to that of veins. These results indicate that the optoacoustic technique can be used for early diagnosis of hematomas and may provide important information for improving outcomes in patients with TBI or stroke (both hemorrhagic and ischemic).

Circulatory shock is a dangerous medical condition, in which blood flow cannot provide the necessary amount of oxygen to organs and tissues. Currently, its diagnosis and therapy decisions are based on hemodynamic parameters (heart rate, blood pressure, blood gases) and mental status of a patient, which all have low specificity. Measurement of mixed or central venous blood oxygenation via catheters is more reliable, but highly invasive and associated with complications. Our previous studies in healthy volunteers demonstrated that optoacoustic systems provide non-invasive measurement of blood oxygenation in specific vessels, including central veins. Here we report our first results of a clinical study in coronary artery bypass graft (CABG) surgery patients. We used a medical-grade OPO-based optoacoustic system developed in our laboratory to measure in real time blood oxygenation in the internal jugular vein (IJV) of these patients. A clinical ultrasound imaging system (GE Vivid e) was used for IJV localization. Catheters were placed in the IJV as part of routine care and blood samples taken via the catheters were processed with a CO-oximeter. The optoacoustic oxygenation data were compared to the CO-oximeter readings. Good correlation between the noninvasive and invasive measurements was obtained. The results of these studies suggest that the optoacoustic system can provide accurate, noninvasive measurements of central venous oxygenation that can be used for patients with circulatory shock.

Circulatory shock may be fatal unless promptly recognized and treated. The most commonly used indicators of shock (hypotension and tachycardia) lack sensitivity and specificity. In the initial stages of shock, the body compensates by reducing blood flow to the peripheral (skin, muscle, etc.) circulation in order to preserve vital organ (brain, heart, liver) perfusion. Characteristically, this can be observed by a greater reduction in peripheral venous oxygenation (for instance, the axillary vein) compared to central venous oxygenation (the internal jugular vein). While invasive measurements of oxygenation are accurate, they lack practicality and are not without complications. We have developed a novel optoacoustic system that noninvasively determines oxygenation in specific veins. In order to test this application, we used lower body negative pressure (LBNP) system, which simulates hemorrhage by exerting a variable amount of suction on the lower body, thereby reducing the volume of blood available for central circulation. Restoration of normal blood flow occurs promptly upon cessation of LBNP. Using two optoacoustic probes, guided by ultrasound imaging, we simultaneously monitored oxygenation in the axillary and internal jugular veins (IJV). LBNP began at -20 mmHg, thereafter was reduced in a step-wise fashion (up to 30 min). The optoacoustically measured axillary oxygenation decreased with LBNP, whereas IJV oxygenation remained relatively constant. These results indicate that our optoacoustic system may provide safe and rapid measurement of peripheral and central venous oxygenation and diagnosis of shock with high specificity and sensitivity.

Circulatory shock is lethal, if not promptly diagnosed and effectively treated. Typically, circulatory shock resuscitation is guided by blood pressure, heart rate, and mental status, which have poor predictive value. In patients, in whom early goaldirected therapy was applied using central venous oxygenation measurement, a substantial reduction of mortality was reported (from 46.5% to 30%). However, central venous catheterization is invasive, time-consuming and often results in complications. We proposed to use the optoacoustic technique for noninvasive, rapid assessment of central venous oxygenation. In our previous works we demonstrated that the optoacoustic technique can provide measurement of blood oxygenation in veins and arteries due to high contrast and high resolution. In this work we developed a novel optoacoustic system for noninvasive, automatic, real-time, and continuous measurement of central venous oxygenation. We performed pilot clinical tests of the system in human subjects with different oxygenation in the internal jugular vein and subclavian vein. A novel optoacoustic interface incorporating highly-sensitive optoacoustic probes and standard ultrasound imaging probes were developed and built for the study. Ultrasound imaging systems Vivid i and hand-held Vscan (GE Healthcare) as well as Site-Rite 5 (C.R. Bard) were used in the study. We developed a special algorithm for oxygenation monitoring with minimal influence of overlying tissue. The data demonstrate that the system provides precise measurement of venous oxygenation continuously and in real time. Both current value of the venous oxygenation and trend (in absolute values and for specified time intervals) are displayed in the system. The data indicate that: 1) the optoacoustic system developed by our group is capable of noninvasive measurement of blood oxygenation in specific veins; 2) clinical ultrasound imaging systems can facilitate optoacoustic probing of specific blood vessels; 3) the optoacoustic system provides noninvasive monitoring during rapid changes in blood oxygenation.

Monitoring of cerebral venous oxygenation is useful to facilitate management of patients with severe or moderate traumatic brain injury (TBI). Prompt recognition of low cerebral venous oxygenation is a key to avoiding secondary brain injury associated with brain hypoxia. In specialized clinical research centers, jugular venous bulb catheters have been used for cerebral venous oxygenation monitoring and have demonstrated that oxygen saturation < 50% (normal range is 55–75%) correlates with poor clinical outcome. We developed an optoacoustic technique for noninvasive monitoring of cerebral venous oxygenation. Recently, we designed and built a novel, medical grade optoacoustic system operating in the near-infrared spectral range for continuous, real-time oxygenation monitoring in the superior sagittal sinus (SSS), a large central cerebral vein. In this work, we designed and built a novel SSS optoacoustic probe and developed a new algorithm for SSS oxygenation measurement. The SSS signals were measured in healthy volunteers during voluntary hyperventilation, which induced changes in SSS oxygenation. Simultaneously, we measured exhaled carbon dioxide concentration (EtCO 2 ) using capnography. Good temporal correlation between decreases in optoacoustically measured SSS oxygenation and decreases in EtCO 2 was obtained. Decreases in EtCO2 from normal values (35-45 mmHg) to 20-25 mmHg resulted in SSS oxygenation decreases by 3-10%. Intersubject variability of the responses may relate to nonspecific brain activation associated with voluntary hyperventilation. The obtained data demonstrate the capability of the optoacoustic system to detect in real time minor changes in the SSS blood oxygenation.

Traumatic brain injury (TBI) and spinal cord injury are a major cause of death for individuals under 50 years of age. In the USA alone, 150,000 patients per year suffer moderate or severe TBI. Moreover, TBI is a major cause of combatrelated death. Monitoring of cerebral venous blood oxygenation is critically important for management of TBI patients because cerebral venous blood oxygenation below 50% results in death or severe neurologic complications. At present, there is no technique for noninvasive, accurate monitoring of this clinically important variable. We proposed to use optoacoustic technique for noninvasive monitoring of cerebral venous blood oxygenation by probing cerebral veins such as the superior sagittal sinus (SSS) and validated it in animal studies. In this work, we developed a novel, medical grade optoacoustic system for continuous, real-time cerebral venous blood oxygenation monitoring and tested it in human subjects at normal conditions and during hyperventilation to simulate changes that may occur in patients with TBI. We designed and built a highly-sensitive optoacoustic probe for SSS signal detection. Continuous measurements were performed in the near infrared spectral range and the SSS oxygenation absolute values were automatically calculated in real time using a special algorithm developed by our group. Continuous measurements performed at normal conditions and during hyperventilation demonstrated that hyperventilation resulted in approximately 12% decrease of cerebral venous blood oxygenation.

Cerebral ischemia after birth and during labor is a major cause of death and severe complications such as cerebral palsy. In the USA alone, cerebral palsy results in permanent disability of 10,000 newborns per year and approximately 500,000 of the total population. Currently, no technology is capable of direct monitoring of cerebral oxygenation in newborns. This study proposes the use of an optoacoustic technique for noninvasive cerebral ischemia monitoring by probing the superior sagittal sinus (SSS), a large central cerebral vein. We developed and built a multi-wavelength, near-infrared optoacoustic system suitable for noninvasive monitoring of cerebral ischemia in newborns with normal weight (NBW), low birth-weight (LBW, 1500 - 2499 g) and very low birth-weight (VLBW, < 1500 g). The system was capable of detecting SSS signals through the open anterior and posterior fontanelles as well as through the skull. We tested the system in NBW, LBW, and VLBW newborns (weight range: from 675 g to 3,000 g) admitted to the neonatal intensive care unit. We performed single and continuous measurements of the SSS blood oxygenation. The data acquisition, processing and analysis software developed by our group provided real-time, absolute SSS blood oxygenation measurements. The SSS blood oxygenation ranged from 60% to 80%. Optoacoustic monitoring of the SSS blood oxygenation provides valuable information because adequate cerebral oxygenation would suggest that no therapy was necessary; conversely, evidence of cerebral ischemia would prompt therapy to increase cerebral blood flow.

Ultrasound imaging is being widely used in clinics to obtain diagnostic information non-invasively and in real time. A high-resolution ultrasound imaging platform, Vevo (VisualSonics, Inc.) provides in vivo, real-time images with exceptional resolution (up to 30 microns) using high-frequency transducers (up to 80 MHz). Recently, we built optoacoustic systems for probing radial artery and peripheral veins that can be used for noninvasive monitoring of total hemoglobin concentration, oxyhemoglobin saturation, and concentration of important endogenous and exogenous chromophores (such as ICG). In this work we used the high-resolution ultrasound imaging system Vevo 770 for visualization of the radial artery and peripheral veins and acquired corresponding optoacoustic signals from them using the optoacoustic systems. Analysis of the optoacoustic data with a specially developed algorithm allowed for measurement of blood oxygenation in the blood vessels as well as for continuous, real-time monitoring of arterial and venous blood oxygenation. Our results indicate that: 1) the optoacoustic technique (unlike pure optical approaches and other noninvasive techniques) is capable of accurate peripheral venous oxygenation measurement; and 2) peripheral venous oxygenation is dependent on skin temperature and local hemodynamics. Moreover, we performed for the first time (to the best of our knowledge) a comparative study of optoacoustic arterial oximetry and a standard pulse oximeter in humans and demonstrated superior performance of the optoacoustic arterial oximeter, in particular at low blood flow.

We developed a noninvasive, optoacoustic diagnostic platform for monitoring of multiple physiologic variables in inpatients and outpatients. One of the most important applications of this platform is noninvasive, rapid assessment and management of circulatory shock, a common condition in critically ill patients. At present, monitoring of circulatory shock requires measurement of central venous blood oxygenation using invasive procedures such as insertion of catheters in central veins. Hemoglobin saturation below 70% in central veins indicates circulatory shock that requires immediate treatment. We built a portable optoacoustic system for noninvasive measurement of central venous oxygenation. In this study we used the optoacoustic system and clinical ultrasound imaging systems for rapid optoacoustic probing of these veins. The optoacoustic system utilizes a custom-made, sensitive optoacoustic probe that was developed in our laboratory for monitoring of blood oxyg enation in deep blood vessels. The studies were performed in human subjects with different geometry (depth, size) of the veins. The ultrasound imaging systems permitted rapid identification of specific blood vessels for optoacoustic probing. We developed a novel algorithm for continuous, real-time, and precise measurement of blood oxygenation in blood vessels. Precision of central venous oxygenation measurement obtained in the study was very high: 1%. Our results indicate that the combination of optoacoustics and ultrasound imaging systems can provide more rapid and accurate assessment and management of the circulatory shock. Keywords : optoacoustics, noninvasive monitoring, central venous oxygenation, circulatory shock, ultrasound imaging 1. INTRODUCTION Circulatory shock, if not promptly diagnosed and effectively treated, is lethal. Resuscitation from hemorrhagic shock is guided by blood pressure, heart rate, and mental status, which have poor predictive value. In severely septic patients , early goal-directed therapy, using as an endpoint superior vena cava (SVC) oxygenation (oxyhemoglobin saturation) >70%, reduced mortality from 46.5% to 30%

Improper placement or positioning of an endotracheal tube may be lethal. Correct placement and positioning of endotracheal tubes is an essential component of life support during resuscitation from cardiac arrest or severe multiple trauma, during mechanical ventilatory support and during most surgical procedures under general anesthesia. To properly ventilate the lungs, endotracheal tubes must be inserted into the trachea rather than the esophagus, must be properly positioned in the mid-trachea and must remain properly positioned. We proposed to use optoacoustic technique for noninvasive monitoring of endotracheal tube placement and positioning. In this work we developed a compact, near infrared optoacoustic system for this application and performed in vitro tests of the system. The tests were performed in tissue phantoms (simulating overlying tissue) with an endotracheal tube. The optoacoustic measurements were noninvasively performed from the skin surface using custom-made optoacoustic probes. The placement and positioning of the endotracheal tubes were monitored with submillimeter axial and millimeter lateral resolution using the optoacoustic system. The obtained data indicate that optoacoustics can provide real-time, precise, cost-effective monitoring of placement and positioning of endotracheal tubes.

One of the most frequently performed blood tests, measurement of total hemoglobin concentration, requires invasive blood sampling. We developed an optoacoustic technique for noninvasive monitoring of total hemoglobin concentration and other blood variables by probing the radial artery or other blood vessels. Recently, we designed and built a focused, wide-band, polymer-based optoacoustic transducer for blood vessel probing with high, submillimeter lateral resolution and incorporated it into a highly portable, laser diode-based optoacoustic system. The focused optoacoustic transducer combines a fiber-optic delivery system and a wide-band piezosensor. First, we experimentally measured transducer parameters (lateral resolution, sensitivity, focal length). To test the transducer capabilities in measurement of total hemoglobin concentration and other blood parameters from blood vessels, we prepared a tissue phantom simulating strongly-scattering tissues with blood vessels of different diameters, spacing, and depths. Optoacoustic signals were acquired from blood at different hemoglobin concentration and oxygenation during transducer scanning over the phantom. In vivo experiments were performed from radial arteries and peripheral veins of different size, depth, and spacing. Submillimeter lateral resolution was obtained in the in vitro and in vivo experiments. The high resolution combined with the wide-band detection of the optoacoustic waves can be used for monitoring of blood variables in blood vessels with high accuracy, sensitivity, and specificity.

Nonlinear effects at SEW excitation in Ag/fullerene thin film structure in Kretschxnann configurationN.N.IVichev*, Yu.Ye.Petrov**, V.A.Yakovlev**Physics Institute, RAS, Vavilov St. 38, 1 17942 Moscow, RussiaPhone: (095)135-03-27, Fax: (O95)1352O-55**Iflfjte of Spectroscopy, RAS, Troitzk, 142092 Moscow Reg., RussiaPhone: (095)334-02-34ABSTRACTDependence of minimum reflectivity angle on incidence light pulse energy at SEW excitation in Kretschmann'sconfiguration was studied. CaF2 prism covered by thin layers of Ag and fullerene was used. Optical constants of fullerenethin layer were found: c'=3.86, s"=0.013 at wavelength 1.055gmINTRODUCTIONSEW excitation in Kretschmann's configuration [1] can be observed by a minimum reflectivity R as a function ofthe angle of incidence 0 of light in the prism with a thin metal film. If we deposit one more thin ifim the position ofthisminimum and shape of R(O) will change. These modifications depend on the later film thickness as well as on its opticalconstants [2]. Optical constants variation in a strong electromagnetic field which are due to the nonlinearity are expectedto result in minimum position shift too. This shift of minimum reflectivity have been observed when SEW were exited byusing grating on bulk single-crystal materials [3]. We have tried to study nonlinearity of thin dielectric films deposited onAg film by SEW excitation at wavelength l.055pm in Kretschmann configuration.SAMPLE PREPARATION AND EXPERIMENTAL SET-UPThermal evaporation in vacuum (10

The thin films of fullerene C 60 and phtalocyanins (Pc): H 2 -Pc, Cu-Pc and Ru-Pc have been evaporated in vacuum on single crystalline quartz and KBr substrates (thicknesses: 0.14 - 2 micrometers ). Infrared reflectivity and transmittance spectra (BOMEM DA3-36, 500 - 5000 cm -1 ) were used for optical constants (refractive index and absorption coefficient) and complex dielectric function determination. In the case of fullerene by dispersion analyses of spectra the oscillator parameters for IR bands were obtained too.

Prepared by radio frequency sputtering superthin Nb and Cu films on (alpha) -quartz and silicon have been studied. We have measured reflectivity and transmittance IR spectra of the films and estimated the imaginary part of their dielectric function from these spectra. The oscillations with a period of 6 angstrom were found on the film thickness dependence of this value for niobium and with a period of 2 angstrom for copper. The same oscillations exhibit in dc resistivity measurements too. We assume that oscillations are due to quantum size effects in the film, because their periods are of the order of the Fermi wavelengths in these metals. Similar effects were observed in surface polariton and surface electromagnetic wave measurements. Temperature measurements of reflectivity and dc resistance have shown that the period as well as the relative amplitude of oscillations are practically temperature independent.

A CCD-type readout system combined with 3-stage electrostatically-focused image intensifier is described. The readout system is based on K580UK80-type microprocessor, 64K of 16 bit words frame memory and 10/12 bit A/D converter.