Combining thermal wave techniques with conventional optical detection methods, such as absorption, reflection, scattering or polarimetry may significantly improve the ability to perform noninvasive monitoring of glucose and other biological compounds. These improvements arise from the attributes of thermal wave technology to spatially localize the measurement to the appropriate region in the tissue or bloodstream, and to substantially reduce other sources of background signal and noise.

The optoacoustic method of monitoring absorbed optical energy distribution in tissues was employed to measure changes in glucose concentration in vivo. Glucose osmotic and hydrophilic properties cause reduction of tissue scattering as a result of glucose concentration increase around scattering particles and fibers. The opto-acoustic (OA) method utilizes time-resolved measurements of laser- induced ultrasonic profile in tissue resembling the distribution of absorbed optical energy. This opto-acoustic profile yields effective optical attenuation coefficient, which decreases with decrease of scattering. Glucose effect has been investigated initially in phantoms resembling optical properties of sclera and polystyrene microspheres water solution colored with potassium chromate and then in sclera in vitro and in sclera of live rabbits. The forward mode of opto-acoustic detection was used in the experiments in vitro. Experiments were performed in UV spectral range at the wavelength of (lambda) equals 355-nm. Experimental results demonstrated that an increase in glucose concentration from 5 mM to 60 mM was expressed in the 3 percent reduction of (mu) _eff in aqueous solution of polystyrene microspheres. The effect of glucose on sclera in vitro was more prominent and measured as 10 percent reduction of (mu) _eff with increase of glucose concentration from 1 mM to 50 mM. It was found that both the amplitude and the profile of OA signal were influenced by mechanical pressure applied to sclera specimen toward the surface of OA transducer. In experiments in live tissue, the backward detection mode was employed, as the only one side access to the tissue surface was available. In experiments in vivo the opto-acoustic profiles were measured in rabbit's sclera before and after intravenous glucose administering. The glucose concentration in rabbit blood was simultaneously measured using commercial device employing chemical analysis of blood. Experimental results demonstrated that a 1 mM increase in glucose concentration resulted in a 3 percent decrease of optical attenuation in rabbit sclera in vivo. Such a pronounced change of optical scattering in sclera in response to physiologic change in blood glucose concentration encourages us to continue measurements in vivo and modeling glucose effect on tissue optics.

Pulsed-photoacoustic spectroscopy in the near IR portion of the optical spectrum was used as a local technique for quantitative monitoring of tissue hemoglobin concentration and its oxygenation state. A pulsed, tunable optical source coupled to a 1mm-diameter optical fiber cable was used to deliver optical energy to the tissue under study. The fiber was placed either on the exterior surface or inserted into the tissue. An ultrasonic signal was produced in the tissue as a result of the absorbed light pulse energy. Since the rate of conversion of laser light energy to heat was rapid and the laser pulse as much shorter than the tissue thermal- diffusion length, the ultrasonic signal amplitude was proportional to the energy absorbed. Spectra of absorbing compounds were obtained by measuring the variation in the acoustic signal with source wavelength. In contrast with near-IR spectroscopic techniques that measure diffuse light transmission and assume knowledge of the pathlength of light traveling through tissues in order to determine the absorption coefficient, the photoacoustic response is produced directly by light absorption. Light scattering merely modifies the spatial distribution of the absorbed energy. Our studies demonstrate that photoacoustic spectra obtained both in vitro and in vivo allow determination of relative changes in the concentration of oxy- and de- oxyhemoglobin.

The second generation of the laser optoacoustic imaging system for breast cancer detection, localization and characterization using a 32-element arc-shaped transducer array was developed and tested. Each acoustic transducer was made of 110-micrometers thick SOLEF PVDF film with dimensions of 1mm X 12.5mm. The frequency band of transducer array provided 0.4-mm axial in-depth resolution. Cylindrical shape of this 10-cm long transducer array provided an improved lateral resolution of 1.0 mm. Original and compact design of low noise preamplifiers and wide band amplifiers was employed. The system sensitivity was optimized by choosing limited bandwidth of ultrasonic detection 20-kHz to 2-MHz. Signal processing was significantly improved and optimized resulting in reduced data collection time of 13 sec. The computer code for digital signal processing employed auto- gain control, high-pass filtering and denoising. An automatic recognition of the opto-acoustic signal detected from the irradiated surface was implemented in order to visualize the breast surface and improve the accuracy of tumor locations. Radial back-projection algorithm was used for image reconstruction. Optimal filtering of image was employed to reduce low and high frequency noise. The advantages and limitations of various contrast-enhancing filters applied to the entire image matrix were studied and discussed. Time necessary for image reconstruction was reduced to 32 sec. The system performance was evaluated initially via acquisition of 2D opto-acoustic images of small absorbing spheres in breast-tissue-like phantoms. Clinical ex-vivo studies of mastectomy specimen were also performed and compared with x-ray radiography and ultrasound.

Our goal is the development of a photo-acoustic instrument for 3D imaging of the microvascular structure in tissue, in real time. A photo-acoustic multi-element detector has been designed, which measures in reflection mode. The light source is a pulsed laser with a wavelength of 532nm and the active piezo-material is PVdF. Using a disk detector we have achieved to reconstruction 3D images with a depth and lateral resolution of 10-20 micrometers and 200 micrometers respectively. With the new probe we expect to reduce the measuring time and to sped up the signal and image processing.

Confocal opto-acoustic transducer (COAT) was developed and applied for detection of early stages of squamous cell carcinoma in hamster model of oral cancer. COAT is a novel imaging modality with optical and acoustic lens utilized for detecting in-depth opto-acoustic front surface transducer is an improved lateral resolution of 60-micrometers . The bandwidth of the confocal opto-acoustic transducer is more than 100 MHz. Therefore, in-depth axial resolution defined by the laser pulse duration and detection system equals 15-micrometers . Imaging was performed at the wavelength of the Nd:YAG laser second harmonic, which provided sufficient depth of monitoring and significant tissue contrast. Correlation of the opto- acoustic images with H and E histology sections in control animals and in animals treated with carcinogenic agent, DMBA, confirmed previous findings that early cancer lesions invisible by the naked eye may be detected with the opto- acoustic tomography. Compact design of COAT allows, in principle, application of the opto-acoustic imaging in any organ of the human digestive system.

Time-resolved optoacoustic tomography is based on thermoelastic pressure generation with shot laser pulses. The pressure wave contains information about the depth and type of light absorbers in the sample. Scanning over the surface of the same yields an optoacoustic image. To measure the pressure wave at the same side as the incident laser pulse, a ring geometry for the pressure transducer was used. The tissue was irradiated through the center of the ring. The ring geometry of the pressure transducer leads to a high directivity because bipolar acoustical signal generated off axis interfere destructively. This improves the spatial resolution of the transducer in scanning direction. The behavior of the detector was calculated for different sample-detector distances. The optoacoustic technique was used to visualize the coagulation of Holmium laser- irradiated chicken breast and to detect a hidden absorber embedded in chicken breast.

To localize and monitor the blood content in tissue we developed a very sensitive double-ring photo-acoustical detector. PvdF has been used as piezo-electric material. In this detector also a fiber for illumination of the sample is integrated. This detector has the advantage that it is very sensitive in the forward direction. A ratio of FWHM to depth of 1:70 can be obtained with this detector.

The time-resolved detection of laser-induced stress transients makes it possible to detect absorbing structures in turbid media. We used optoacoustic technique for investigation of blood vessels in tissue. The position in depth and the size of absorbers in gel phantoms and vessels in muscle tissue were measured. The acoustic waves were induced by 15-ns 1064-nm pulses of Q-switched Nd:YAG laser. Experimental results have shown that the blood vessels can be visualized at depth up to 10 mm at that wavelength.

Photoacoustic imaging may be used to detect tumor masses in biological tissue. In particular, time of flight measurements of the photoacoustic waves may indicate tumor location. Here we use time of flight information to localize spherical photoacoustic sources in tissue phantoms. A Q- switched, frequency-doubled Nd:YAG laser operating at 532nm with a pulse duration of 5 ns irradiated absorbing spheres 2 mm in diameter. The spheres were in mineral oil or turbid acrylamide blocks. A PVDF acoustic transducer was built and used to detect the acoustic waves. The position of the detector was translated so that the time of flight information from two acoustic waveforms from the source could be correlated by a convolution algorithm. This convolution result in a 2D map indicating the position of the source. Source location was indicated to within 5 percent of the true location for acoustic propagation distances of 20 mm. An image source is also indicated when the true source was in proximity to a reflecting boundary.

An all-optical system for the detection of photoacoustic transients is under development for photoacoustic imaging applications. The sensing mechanism is based upon the detection of acoustically-induced variations in the optical thickness of a Fabry-Perot polymer film interferometer and provides an alternative to piezoelectric based detection methods. A key advantage is that the sensing geometry is defined by the area of the polymer sensing film that is optically addressed. This offers the prospect of obtaining sufficiently small element sizes and interelement spacing to e ply the synthetic focusing techniques of phased arrays for image reconstruction. The optical nature of detection also allows for a transparent sensor head through which the excitation laser pulses can be transmitted for backward-mode photoacoustic imaging. Preliminary work has shown that the detection sensitivity and bandwidth are comparable to wideband piezoelectric PVDF ultrasound transducers with the prospect of achieving substantially smaller element sizes.

Among diffusion methods, photothermal radiometry (PTR) has the ability to penetrate and yield information about an opaque medium well beyond the range of conventional optical imaging. Owing to this ability, pulsed-laser PTR has been extensively used in turbid media such as biological tissue to study the sub-surface deposition of laser radiation, a task which may be difficult or impossible for conventional optical methods due to excessive scattering and absorption. In this work, the optical and thermal properties of tissue- like materials are observed using frequency-domain IR photothermal radiometry. An approximate 3D heat conduction formulation with the use of 1D optical diffusion is developed to derive a turbid frequency-domain PTR model. The agreement in the absorption and transparent scattering coefficients of model phantoms is investigated. The present opto-thermal model for frequency-domain PTR may prove useful for non-contact, non-invasive, in situ measurement of optical properties of tissues and other multiply-scattering media.

Frequency-domain IR photothermal radiometry is introduced as a dynamic dental diagnostic tool and its main features are compared with conventional laser luminescence for quantifying sound and defective enamel. A high-spatial- resolution dynamic experimental imaging set-up, which can provide simultaneous measurements of laser-induced frequency-domain IR photothermal radiometric and luminescence signals form defects in teeth, has been developed. Following optical absorption of laser photons, the new set-up can monitor simultaneously and independently the non-radiative conversion via IR photothermal radiometry; and the radiative de-excitation via luminescence emission.

Ultrasound-modulated optical tomography in biological tissue was studied. An ultrasonic beam was focused into a biological tissue sample to modulate the laser light passing through the ultrasonic beam inside the tissue. The speckle field formed by the transmitted laser light was detected by a CCD camera with the source-synchronous-illumination lock- in technique. The ultrasound-modulated laser light reflects the local optical and mechanical properties within the ultrasonic beam and can be used for tomographic imaging of the tissue. We implemented frequency-swept modulation to obtain spatial resolution along the ultrasonic axis. 2D images of biological tissue were successfully obtained with both single frequency modulation and frequency-swept modulation. 3D images could be acquired as well in principle.

An ultrasonic vibration potential is generated when an acoustic wave propagates in an ionic or colloidal suspension. Measurement of the potential as an ultrasonic wave propagates in a body offers the possibility of a method of imaging. The resolution of the method ultimately is limited by the wavelength of the ultrasound; the contrast of the technique will depend on inertial quantities and the relative zeta potentials of the irradiated regions. The prospects for tissue imaging using the ultrasonic vibration potential are discussed.

We have developed instrumentation for measuring the tissue- absorption properties of radio waves in the human body using thermoacoustic interactions. The imaging principles upon which this instrumentation is based are applicable to other irradiation sources, such as visible and IR. We present the imaging reconstruction methodology that we have developed for mapping radiation absorption pattern sin 3D. Both simulated and experimental data are used to illustrate imaging principles.

Scanning thermoacoustic tomography based on microwave- induced thermoacoustic waves was studied. 2D images of approximately 50-mm thick biological tissue samples were obtained experimentally. The thermoacoustic signals were also simulated theoretically. The image resolution was significantly improved compared with purely microwave imaging.

We demonstrate application of an IR imaging technique for non-contact determination of thermal diffusivity of biological materials. The IR method utilizes pulsed laser excitation to produce an initial 3D temperature distribution in tissue, and records IR images of subsequent heat diffusion. The theoretical model assumes the time-dependent temperature increase following pulsed laser exposure occurs due to independent heat diffusion in longitudinal and lateral directions. A nonlinear least-squares algorithm is used to compute the lateral point spread function for a pair of recorded IR images and determine thermal diffusivity of a test specimen. Application of the method was demonstrated using tissue phantom s and ex-vivo samples of hydrated cartilage.

We have performed pulsed photothermal radiometric measurements of thermal diffusivity of silica-gel on thin- layer chromatography plates at two different IR wavelength regions ane obtained values in the region of D equals 0.2 mm²/s. We then proceeded to depth profiling of TLC plates with photoacoustic measurements with modulated excitation using IR and visible excitation.

In this work, we show a particular setup, which is based on the conventional photoacoustic cell, to measure thermal effusivity of human skin in-vivo and in-situ. We measure the changes of thermal effusivity due to the absorption of sunscreen into the skin and these values are compared with those from an adjacent sample of clean skin. This experiment was performed on a volunteer's forearm and stainless steel as the thermally thin absorption surface. The values for this parameter are in good agreement with those reported in the literature. Besides the measurements described above, with the same setup we got the thermal effusivity of the sunscreen itself as a reference parameter. R

Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

A further study is given of photoacoustic (PA) drug delivery technologies using an Er:YAG laser, with the main emphasis being placed on the laser perforation of skin and on PA impregnation using an additional covering quartz plate. A mathematical model based on Fick's law for PA impregnation with regard to a free and rigid interface is considered. The histological examination of the perforated guinea-pig skin ex vivo shoed that a powerful PA wave forced skin epidermis to be bent inwards. In biopsies taken 15 min later the nuclei pyknosis of epidermis cells lining the perforated channel was observed. In biopsies obtained 36 hours later an insignificant necrotic lesion remained, whereas 120 hours laser the cells recovered. I twas shown experimentally that the PA signal increased 30 times after applying a quartz plate over the drug solution, which substantially enhanced drug penetration through the skin .The dependancies were obtained of the penetration depth of the haematoporphyrin derivative photosensitizer versus the number of laser pulses and the pressing force applied to the quartz plate. The chromatographic fractionation of Diprospan and Dexamethasone hormonal preparations prior to and after the action of 200 Er:YAG laser-induced PA waves demonstrated that no additional chemical agents resulting from drug dissociation were detected. The application of laser drug delivery methods in respect of treating dermatological diseases is also discussed.

An optoacoustic device consisting of YAG laser and a measurement cell with an attached piezotransducer was used to detect atmospherical microparticles as well as artificial latex suspension. Monte Carlo simulation was used to predict the statistical parameters of the acoustical response.

In burn surgery necrotic tissue has to be removed prior to skin grafting. Tangential excision causes high blood loss and destruction of viable tissue. Pulsed IR laser ablation can overcome these problems because of its high precision and the superficial coagulation of the remaining tissue. We realized an acoustic on-line monitoring system for a selective removal of necrotic tissue that is based on the detection of the energy of the acoustic signal produced during ablation. We developed a PC based system for data acquisition and real-time data analysis running at laser repetition rates of more than 30 Hz, and studied free- running Er:YAG laser ablation of burned skin and stacked gelatin samples which served as reproducible tissue models. Spectral analysis of the ablation noise showed that the optimum tissue specificity of the acoustic energy can only be achieved if the bandwidth of the acoustic transducer range up to more than 300 kHz. We were able to detect the boundary between gelatin layers of different water content by applying a threshold criterion for the relative increase of the acoustic energy with respect to the first laser pulse at each ablation site. Healthy and burned parts of skin samples as well as necrotic and viable tissue layers in second degree burns could be discriminated, in agreement with the result of histologic examinations. Superficial vascular structures could be distinguished fro surrounding burned tissue with good spatial resolution.

The major limitation in sensitivity of the optical tomography is associated with strong optical attenuation in human tissues. Opto-acoustic tomography overcomes this limitation utilizing detection of acoustic waves instead of detection of transmitted photons. Exceptional sensitivity of the opto-acoustic tomography allows early detection of small tumors located dep in human tissues, such as breast. This paper demonstrates that an optimally designed opto-acoustic imaging system can detect early 1-mm tumors with minimal blood content of only 7 percent at the depth of up to 7-cm within the breast attenuating laser irradiation 3.3 times per each 1-cm of its depth. A theoretical consideration of the ultimate sensitivity of piezo-detection in a wide ultrasonic frequency band is developed. The detection sensitivity is presented as a function of the ultrasonic frequency, tumor dimensions and optical absorption coefficient. Comparative analysis of piezo and optical interferometric detection of opto-acoustic transients is presented. The theoretical models of piezo detection were developed for the open-circuit and short-circuit schemes of operation. The ultimate sensitivity limited by thermal noise of electric capacitor of the piezo-element was estimated. It was shown that the limit of detection depends on the frequency band, the electric capacity of the transducer and the sped of sound in the piezo-element. Comparative analysis of various piezo-materials was made from the point of view of their utility for sensitive opto-acoustic detection.

Optoacoustic imaging uses thermoelastic waves generated by short laser pulses to localize structures with preferential light absorption inside a material. The acoustic waves are directly generated in absorbing structures and are detected outside the sample with a wide-band ultrasonic transducer. Image reconstruction is usually done by backprojection of temporal ultrasound signals that are taken at different positions. As an alternative, we present a method where the acoustic field caused by thermoelastic excitation is captured as a snapshot in a plane, using an optical reflectance based detection principle. Image reconstruction is accomplished by backprojection of the detected 2D stress distributions into the sample volume, using the delay times at which the snapshots were taken after the laser pulse. 2D stress signals and image reconstruction are demonstrated in simulations and in experiments, where small objects like hairs are irradiated with laser pulses of 6 ns duration. The main advantages of this system are the high spatial resolution that can be achieved with the optical sensing technique and the possibility to irradiate the sample directly through the detector plane. This enables front surface detection of the optoacoustic signals, which is especially important if structures close to the tissue surface are to be imaged.

We discuss the utility of wavelet transform methods in signal processing in general, and in particular, demonstrate the technique in optoacoustic applications. In several optoacoustic experiments with different samples, we have successfully enhanced the signal to noise ratios. Wavelet transforms optimize resolution by utilizing a tailored, variable time-window in different frequency regions. The technique's great advantage lies in the fact that the wavelet transform adds some redundancy to the original signal, and some desired features can be enhanced in the transformed space. In addition, proper choice of the basis set allows a sparse representation of the signal. Therefore, even when some components are suppressed in the transformed space, the signal itself can maintain its fidelity. This technique has great potential in biomedical optoacoustics, such as medical image processing and signal denoising. We use the wavelet transform technique to resolve acoustic echoes in the time-dilation space. White noise was removed by the wavelet shrinkage method. This processing was used to analyze several experimental results. These include optoacoustic measurements in solid samples as well as in biological tissues.

The results of theoretical and experimental investigations of optoacoustic method for 2D tomography of biological objects are presented. The optimal bandwidth for acoustic signal receiving form depth about some centimeters is estimated from the viewpoint of sensitivity and spatial resolution. The frequency range 1-10 MHz was demonstrated to be most advantageous.

Photothermal technique for light microscopy is reported as the new tool for quantitative analysis of single living cell structural and functional properties. Probe laser illumination with phase contrast method allows to visualize thermal field being induced in cell due to absorption of pump laser radiation. In our set up the cell is pumped by the pulsed laser at 532 nm, 10 ns, 0.01-0.4 mJ. The source of probe beam is a pulsed dye laser which forms cell image. Fully automated image cytometer with acquisition rate 1cell/s is described. An acquired cell image is considered as spatially and temporally resolved cell response to non- specific load being induced with a pump laser. Thus we introduce photothermal image cytometry which may be applied for investigation of mechanisms of photodamage, single cell dosimetry, cell functions and structure and thermal phenomena at cell level.

Blood group antigens on a cell were measured by a new microscopic method, i.e. thermal lens microscopy which involves spectrometry using a laser-induced thermal-lens effect. The blood group antigen was immunologically stained using antibody labeled with colloidal gold. Human leukocyte antigens (HLA) on lymphocytes and mononuclear leukocytes were observed by the thermal lens microscope, and Lewis blood group antigens on erythrocytes and polymorphonuclear leukocytes were also observed. The antigen distribution on each cell-surface was imaged using this technique. In spite of convex surface of living cells, colloidal gold was correctly quantified by adjusting the deviation of the focal point of the probe laser by the phase of the signal. In the measurement of leukocyte antigens, antigens of HLA-A, -B, -C loci on the lymphocytes were identified and quantitated by using a single cell. The image of HLA-A, -B, -C antigen distribution on a mononuclear leukocyte was obtained. In the measurement of erythrocyte antigens, a small quantity of Lewis antigens was detected on the cord erythrocytes. Localized small quantities of membrane antigens are better quantitated without extraction or cytolysis. Our thermal lens microscope is a powerful and highly sensitive analytical tool for detecting and quantitating localized antigens in single cells and/or cell-surface-associated molecules.

Important features of laser photoacoustic (PA) spectrometers employed in trace gas monitoring and multicomponent gas analysis are discussed. Narrowband laser sources with wide tunability in the mid-IR range are employed. We have developed and applied different laser-based PA spectrometers. These arrangements are briefly presented and the excellent detection performance in terms of sensitivity and specificity is illustrated by various examples. A high- pressure CO₂ laser, an optical parametric oscillator (OPO)-based difference frequency generation system and aline-tunable CO₂ laser, implemented in a trailer for in situ measurements, are employed as laser source. Novel PA cells and microphone arrays with up to 80 individual microphones have been developed. A detection limit of 10^-9 cm^-1 atm^-1 and a large dynamic range of seven orders of magnitude have been achieved with an extracavity multipass resonant PA cell. Examples to be presented include in situ multicomponent measurements on dynamically controlled atmospheres in fruit storage chambers or analyses of benzene-toluene-p-xylene mixtures.

Photoacoustic spectroscopy is a sensitive, on-line and non- invasive tool to monitor concentrations of trace gases in ambient air. With the appropriate high power lasers in the mid-IR wavelength region gas mixtures can be analyzed, at and below the part per billion level. Within the development of novel IR laser sources, a continuous wave optical parametric oscillator based on periodically poled lithium niobate in combination with photoacoustic detection has been applied to detect traces of several hydrocarbons in nitrogen. At an idler wavelength of around 3.3 micrometers , the cw OPO produced approximately 300 mW of single mode radiation. Preliminary results show detection limits on methane, ethane, butane and pentane of around 1 ppb. This trace gas detector will be used within medical applications. E.g., the trace gas composition of exhaled air is able to give information about a wide variety of processes in human body. In addition, such analysis has the potential to monitor processes non-invasive, on-line and fast for diagnostic purposes related to acute or chronic diseases.

Optoacoustic monitoring of tissue optical properties and speed of sound in real time can provide fast and accurate feedback information during thermotherapy performed with various heating or cooling agents. Amplitude and temporal characteristics of optoacoustic pressure waves are dependent on tissue properties. Detection and measurement of the optoacoustic waves may be used to monitor the extent of tissue hyperthermia, coagulation, or freezing with high resolution and contrast. We studied real-time optoacoustic monitoring of thermal coagulation induced by conductive heating and laser radiation and cryoablation with liquid nitrogen. Q-switched Nd:YAG laser pulses were used as probing radiation to induce optoacoustic waves in tissues. Dramatic changes in optoacoustic signal parameters were detected during tissue freezing and coagulation due to sharp changes in tissue properties. The dimensions of thermally- induced lesions were measured in real time with the optoacoustic technique. Our studies demonstrated that the laser optoacoustic technique is capable of real-time monitoring of tissue coagulation and freezing front with submillimeter spatial resolution. This may allow accurate thermal ablation or cryotherapy of malignant and benign lesions with minimal damage to normal tissues.

To improve the safety and efficacy of thermal therapy, it is often necessary to map tissue temperature in real time with submillimeter spatial resolution in order to accurately control the boundaries of heated regions and minimize thermal damage to surrounding normal tissues. Current imaging modalities fail to monitor tissue temperature in real time with high resolution and accuracy. We propose to use optoacoustic techniques for accurate, real-time monitoring of tissue temperature with high spatial resolution. Our previous studies demonstrated that the efficiency of optoacoustic wave generation in tissues increases linearly with temperature during uniform heating. In this study, we induced temperature gradients in treated samples and monitor temperature distribution in tissue using optoacoustic technique. Fundamental harmonic of Q-switched Nd:YAG laser was used for optoacoustic wave generation and probing of tissue temperature while the tissue temperature was also monitored with a multisensor temperature probe inserted in the samples. Good agreement between optoacoustic dat and the tissue temperature as recorded via the probe was demonstrated. The optoacoustic techniques was capable of real-time temperature distribution monitoring with submillimeter resolution and high accuracy.

Esophageal cancer patients often present a highly inflamed esophagus at the time of treatment by photodynamic therapy. Immediately after treatment, the inflamed vessels have been shut down and the esophagus presents a white surface. Optoacoustic imaging via an optical fiber device can provide a depth profile of the blanching of inflammation. Such a profile may be an indicator of the depth of treatment achieved by the PDT. Our progress toward developing this diagnostic for use in our clinical PDT treatments of esophageal cancer patients is presented.

This article presents the further developments of combined laser-ultrasound medical technologies with paying attention the possibility ultrasound in surgery and therapy. The analyses of main effects at the low frequency ultrasonic treatment of biotissues including cavitation, acoustic streams, acoustic pressure, mechanical influence etc are analyzed. The main promising areas of application of low frequency ultrasound are considered including bactericidal treatment of infections wounds, spray treatment of wounds in head and neck surgery, tumor treatment etc. In particular the clinical result of using ultrasonic devices based on imposing ultrasonic oscillations in a range of 22-66 kHz on a cutting instrument with a special form, radiation intensity up to 10 W/cm² and oscillation amplitude up to 40-60 micrometers with respect to oncology for halt bleeding from a tumor, liquidating pain, acoustic denervation are presented. Some limitation of medical application of ultrasound are discussed and perspective combination with laser for increasing efficiency of new combined technologies are found. Among them: combination photodynamic therapy and ultrasonic treatment of tumors, laser-ultrasonic treatment of infections wounds including using spray, laser-ultrasonic drug delivery. The preliminary result of experimental study of some of above-mentioned technologies are presented.