Elena V. Savateeva

Backward mode detection of laser-induced wide-band ultrasonic transients with optoacoustic transducer

Time-resolved piezoelectric detection of wide-band ultrasonic transients induced by laser pulses in absorbing medium was studied. An optoacoustic transducer was developed for measuring the profiles of ultrasonic transients propagating in backward direction out of the laser-irradiated medium. For this purpose, an optical fiber for delivery of laser pulses to the surface of absorbing medium and a wide-band lithium niobate acoustic transducer were incorporated in one compact system, optoacoustic front surface transducer (OAFST). The transducer possesses temporal resolution (rise time) of 3.5 ns, low effective thermal noise pressure (10 Pa), and high sensitivity of piezoelectric detection (10 μV/Pa) over the ultrasonic frequency range from 1 to 100 MHz. Nd:YAG laser pulses at 355 nm were employed to generate distribution of acoustic sources in water solutions of potassium chromate with various concentrations. A temporal course of ultrasonic transients launched into an optically and acoustically transparent me...

Enhancement of optoacoustic tissue contrast with absorbing nanoparticles

Laser induced phase transition in the water surrounding absorbing nanoparticle results in dramatic enhancement of the thermoacoustic efficiency and excitation of high- amplitude pressure waves. Feasibility study was performed in tissue phantoms. Experiments supported with theoretical model demonstrated possibility to increase the efficiency of optoacoustic generation in tissue up to two orders of magnitude by application of absorbing carbon and gold nanoparticles.

Imaging of layered structures in biological tissues with optoacoustic front surface transducer

Optoacoustic tomography is a promising technique for imaging skin layered structures and vascular and pigmented lesions in vivo. The imaging of skin is complicated by necessity to perform laser irradiation and acoustic detection from the same site at the surface. We designed an opto-acoustic transducer incorporating a fiber-optic light delivery system and a LiNbO3 piezoelectric detector in one device. The results of test experiments in phantoms, chicken cockscomb, and human hand yielded the following parameters of the opto-acoustic transducer: (1) sensitivity of 0.98 V/bar, (2) temporal resolution of acoustic detection of 5 ns. This fast response time allows one to achieve an in-depth resolution of 10 - 15 micrometer. A small size of the detector provides lateral resolution of 200 micrometer. Feasibility studies demonstrated that the current design of the optoacoustic transducer permits monitoring of the light absorbing heterogeneities at the dept up to 4 mm. The principle scheme of the opto-acoustic transducer design, theoretical background and experimental testing is presented. Theoretical model of the wide-band ultrasonic detection is developed. The principles of the opto- acoustic image reconstruction under conditions of significant diffraction of acoustic wave are described. A basic algorithm for reconstruction of 3-D images from the laser-induced acoustic waves recorded in backward mode is also presented.

Optoacoustic tomography of breast cancer with arc-array transducer

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.

Optoacoustic imaging of blood for visualization and diagnostics of breast cancer

Aggressive malignant tumors may be diagnosed based on relative concentration of oxyhemoglobin and deoxyhemoglobin in the tumor microvasculature. Optoacoustic images of breast cancer and prostate cancer may be acquired at two laser wavelengths matching maximum of oxyhemoglobin (1064-nm, Nd:YAG laser) and deoxyhemoglobin (760-nm, Alexandrite laser). Two optoacoustic systems operating in forward and backward mode respectively for breast cancer and prostate cancer detection, employing arrays of ultravide-band piezoelectric transducers and multichannel electronics was described. After systems testing and calibration in phantoms, initial experiments were performed on patients with suspicious tumors. Quantitative analysis of two-color optoacoustic images was correlated with biopsy and histology. Possibility for tumor differentiation was demonstrated.

Noninvasive detection and staging of oral cancer in vivo with confocal optoacoustic tomography

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.

Optical properties of blood at various levels of oxygenation studied by time-resolved detection of laser-induced pressure profiles

Time resolved detection of laser-induced pressure profiles permits sensitive and high-resolution measurements of distribution of absorbed optical energy in optically scattering and opaque media, such as blood. We report experimental measurements of optical properties in the whole blood of animals at various levels of oxygen saturation and analytical calculations of relative concentrations of oxy- and deoxy- hemoglobin. The results show that optoacoustic profiles are sensitive to small variations in optical properties of blood. When measured with absolutely calibrated acoustic transducers at two different laser wavelengths, 757-nm and 1064-nm, the total hemoglobin concentration and its oxygenation level can be determined from the optoacoustic profiles. The value of thermoacoustic efficiency of pressure wave generation by laser irradiation was also determined from experiments. Erythrocyte sedimentation and aggregation rate was studied, since these phenomena affect spatial distribution of optical energy in blood upon laser irradiation. Erythrocyte sedimentation rate was calculated from kinetic changes in optoacoustic profiles. The results encourage development of various applications of optoacoustic spectroscopy in monitoring of blood properties in vitro and in human tissues.

Opto-acoustic monitoring of blood optical properties as a function of glucose concentration

Time-resolved optoacoustic (OA) method was employed to measure changes in glucose concentration in the whole and diluted blood. An increase of the glucose level in tissue results in a corresponding decrease of optical scattering. Relative changes in tissue optical scattering can be obtained by measuring the effective optical attenuation coefficient, μeff by exponential fitting of the time-resolved optoacoustic profiles. Glucose effects in blood have been investigated using the forward mode of OA detection performed in the visible (at the wavelength, λ=532 nm) and near infrared (λ=1064 nm) spectral ranges. In our previous set of experiments, the OA studies performed in model media in vitro and biological tissue (sclera) in vivo demonstrated gradual reduction of optical scattering with the increase in glucose level. The present study has supported our previous observations. However, one novel effect was observed comprised of a transient increase in μeff during the first 5-10 minutes after injection of glucose. This phenomenon may be explained by changes in erythrocytes shape and size as a result of their adaptation to hyperglycemic conditions. Our observation was supported by light microscopy images of red blood cells under normal and hyperglycemic conditions. With glucose concentration changing rapidly (osmotic shock), any small reduction in µeff due to the glucose-induced decrease of relative refraction index of blood, can be compensated or even overwhelmed by the increase in µeff due to erythrocyte shrinkage and/or spherulation. Further cellular adaptation to glucose make erythrocytes return to their normal shape of biconcave disks about 7-μm in diameter. The kinetics of the effective optical attenuation was studies in response to glucose injection in order to better understand the mechanisms of erythrocyte adaptation to osmotic shock and to determine the time course of RBCs adaptation to various glucose concentrations. Finally, Mannitol as alternative osmolyte, which cannot penetrate through the RBC membrane, was used in the study. The effect of Mannitol on optical properties of blood was found to be even more pronounced compared to the effect of glucose. In this study, blood was chosen as an experimental medium with perspective of using the optoacoustic monitoring of glucose concentration either inside veins or in tissues that are well supplied with blood. The results of this study help in designing an optoacoustic measurement protocol for monitoring blood glucose in diabetic patients.

Optoacoustic supercontrast for early cancer detection

Thermal mechanism is fundamental for the generation of ultrasonic waves in a course of absorption of laser radiation. Its efficiency is relatively low, but increases significantly with temperature (thermal non-linearity). If the phase transition of the irradiated medium occur, the efficiency may exceed its linear regime value several orders of magnitude. The idea of optoacoustic supercontrast for early cancer detection is based on this fact. We performed feasibility studies and describe requirements to and properties of the optoacoustic supercontrast agent based on nanoscopid particles. The results of the preliminary experiments with the metal and carbon nanoparticles as optoacoustic generation up to three orders of magnitude under irradiation conditions of laser optoacoustic imaging in the depth of human tissue.

Monitoring glucose in vivo by measuring laser-induced acoustic profiles

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 rabbits 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.