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Papers by Alexander Oraevsky

Research paper thumbnail of Method of laser activated nano-thermolysis for elimination of tumor cells

Cancer Letters, 2006

We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activ... more We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activated Nanothermolysis and propose this method for purging of bone marrow and blood transplants. K562 and human lympholeukemia cells were eliminated in experiments by laser-induced micro-bubbles that emerge inside individual target cells around selectively formed clusters of light-absorbing gold nanoparticles. Pretreatment of tumor cells with specific monoclonal antibodies and Igconjugated 30-nm gold particles allowed the formation of clusters of 10-20 on the surface of cell membrane. Electron microscopy found the nanoparticulate clusters inside the cells. Total (100%) elimination of K562 cells targeted with specific antibodies was achieved with single laser pulses with optical fluence of 5 J/cm 2 at the wavelength of 532 nm without damage to the same cells targeted without specific antibodies. Total elimination of human lymphoblasts from suspension of normal stem cells was achieved by a single laser pulse with the optical fluence of 1.7 J/cm 2 , while the damage level of normal cells was 16%. q

Research paper thumbnail of Lantcet: Novel laser nanotechnology for graft purging

Biology of Blood and Marrow Transplantation, 2006

We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activ... more We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activated Nanothermolysis and propose this method for purging of bone marrow and blood transplants. K562 and human lympholeukemia cells were eliminated in experiments by laser-induced micro-bubbles that emerge inside individual target cells around selectively formed clusters of light-absorbing gold nanoparticles. Pretreatment of tumor cells with specific monoclonal antibodies and Igconjugated 30-nm gold particles allowed the formation of clusters of 10-20 on the surface of cell membrane. Electron microscopy found the nanoparticulate clusters inside the cells. Total (100%) elimination of K562 cells targeted with specific antibodies was achieved with single laser pulses with optical fluence of 5 J/cm 2 at the wavelength of 532 nm without damage to the same cells targeted without specific antibodies. Total elimination of human lymphoblasts from suspension of normal stem cells was achieved by a single laser pulse with the optical fluence of 1.7 J/cm 2 , while the damage level of normal cells was 16%. q

Research paper thumbnail of Optoacoustic microscopy using laser beam deflection technique

Photons Plus Ultrasound: Imaging and Sensing 2014, 2014

ABSTRACT Optoacoustic microscopy (OAM) is an emerging technology combining the beneficial feature... more ABSTRACT Optoacoustic microscopy (OAM) is an emerging technology combining the beneficial features of optical contrast and ultrasound resolution, to form a hybrid imaging technique capable of multi-scale, high-contrast and high-resolution imaging through optically scattering biological tissues. In the past 15 years, two system modifications have been developed for optoacoustic / photoacoustic microscopy: acoustic-resolution AR-OAM and optical-resolution OR-OAM. Typically, acoustic resolution systems can image deeper tissues structures, however, with resolution at least an order of magnitude worse than the systems of optical-resolution. It would be attractive for variety of biomedical applications to attain high (submicron) resolution at a depth exceeding the present limit of the optical resolution optoacoustic microscopy. Here we introduce a novel, all-optical method for OAM, in which not only thermal energy deposition, but also optoacoustic signal detection is achieved optically. In our design the probe laser beam was used as an ultrawide-band ultrasonic transducer. In this method the acoustic pressure wave amplitude is proportional to the angle of deflection of the probing CW laser beam incident on a balanced dual photodiode. Such laser beam deflection (LBD) method overcomes the limitations of conventional piezoelectric ultrasound transducers and optical interferometers. LBD method allows one to use high numerical aperture objectives for better focusing, avoid distortions associated with the system elements that separate optical and acoustic paths, and provides better sensitivity than any optical interferometer. It also provides a non-contact method that is insensitive to optical and acoustic artifacts typical of backward mode of optoacoustic imaging. The LBD sensitivity depends on a large number of system parameters such as probe beam power, spot size, interaction length, optical refraction index of the coupling medium, laser wavelength, photodiode sensitivity, proximity to the optoacoustic source, and thus, can be optimized. The basic setup of OR-LBD-OAM shows high sensitivity competitive with commercial ultrasonic transducers. We report first images of biological cells and tissues obtained using this technique.

Research paper thumbnail of <title>Optoacoustic imaging system with improved collection efficiency</title>

Photons Plus Ultrasound: Imaging and Sensing 2011, 2011

We introduce a novel experimental design for non-invasive scanning optoacoustic microscopy that u... more We introduce a novel experimental design for non-invasive scanning optoacoustic microscopy that utilizes a parabolic surface for ultrasound focusing. We demonstrate that off-axis parabolic mirrors made of sufficiently high acoustic impedance materials work as ideal reflectors in a wide range of apertures and provide lossless conversion of a spherical acoustic wavefront into a plane wave. We further test the performance of a custom optoacoustic imaging setup which was developed and built based on these principles. The achieved resolution limit of 0.3 mm, with NA of 0.5 and the transducer bandwidth of 5 MHz, matches the resolution limit defined by diffraction. Although further improvements of current experimental setup are required to achieve resolution similar to leading microscopy systems, this proof-ofconcept work demonstrates the viability of the proposed design for optoacoustic microscopy applications.

Research paper thumbnail of Highly purified biocompatible gold nanorods for contrasted optoacoustic imaging of small animal models

Nanoscience and nanotechnology letters (Print), 2012

We developed a methodology for high yield synthesis of gold nanorods (GNR) with narrow band optic... more We developed a methodology for high yield synthesis of gold nanorods (GNR) with narrow band optical absorption centered at 760 nm. GNR were purified from hexadecyltrimethylammonium bromide (CTAB) and coated with polyethylene glycol (PEG). The molar ratio between GNR and PEG (1÷50000) was optimized to make the conjugate a biocompatible PEG-GNR contrast agent for optoacoustic (OA) imaging. In vitro toxicity studies showed no significant change in survival rates of cultured normal (IEC-6, MDCK) and cancer (SKBR3 and HEPG2) cells after they were incubated with 0.125 to 1.25 nM PEG-GNR solutions. In vivo toxicity studies in nude mice showed no pathological changes in liver after the IV injection of GNR. Significant enhancements of OA contrast in comparison to images of untreated mice were observed 1 hour after the GNR injection in a dose of 20 mg gold per kg of body mass.

Research paper thumbnail of 3D laser optoacoustic ultrasonic imaging system for research in mice (LOUIS-3DM)

Photons Plus Ultrasound: Imaging and Sensing 2014, 2014

ABSTRACT In this work we introduce an improved prototype of three-dimensional imaging system that... more ABSTRACT In this work we introduce an improved prototype of three-dimensional imaging system that combines optoacoustic tomography (OAT) and laser ultrasound tomography (LUT) to obtain coregistered maps of tissue optical absorption and speed of sound (SoS). The OAT scan is performed by a 360 degree rotation of a mouse with respect to an arc-shaped array of ultrasonic transducers. A Q-switched laser system is used to establish optoacoustic illumination pattern appropriate for deep tissue imaging with a tunable (730-840 nm) output wavelengths operated at 10 Hz pulse repetition rate. A 532 nm wavelength output, being mostly absorbed within a narrow superficial layer of skin, is used to outline the visualized biological object. Broadband laser ultrasound emitters are arranged in another arc pattern and are positioned opposite and orthogonal to the array of transducers. This imaging geometry allows reconstruction of volumes that depict SoS distributions from the measured time of flight data. The reconstructed LUT images can subsequently be employed by an optoacoustic reconstruction algorithm to compensate for acoustic wavefield aberration and thereby improve accuracy of the reconstructed images of the absorbed optical energy. The coregistered OAT-LUT imaging is validated in a phantom and live mouse using a single-slice system prototype.

Research paper thumbnail of Biomedical optoacoustics(San Jose CA, 25-27 January 2000)

Research paper thumbnail of Biomedical optoacoustics IV(San Jose CA, 26-27 January 2003)

Research paper thumbnail of Optoacoustic systems for functional and molecular imaging in clinical and preclinical research

2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009

ABSTRACT Optoacoustic imaging systems provide a unique opportunity to visualize, with high spatia... more ABSTRACT Optoacoustic imaging systems provide a unique opportunity to visualize, with high spatial resolution, the distribution of optical energy in opaque biological tissues and even to visualize the distribution of optically absorbing molecules in tissues. Since hemoglobin of blood is the main tissue chromophore that dominates optical absorption in the near-infrared spectral range, the optoacoustic imaging is well suitable for visualization of blood distributions associated with various diseases, such as cancer and atherosclerosis. Design of optoacoustic systems for two-dimensional and three-dimensional imaging and their applications in clinical and preclinical oncology will be presented.

Research paper thumbnail of Future Biomedical Applications of Optoacoustic Tomography

Research paper thumbnail of 3D Optoacoustic Tomography: From Molecular Targets in Mouse Models to Functional Imaging of Breast Cancer

Research paper thumbnail of High contrast optoacoustical imaging using non-spherical nanoparticles

Research paper thumbnail of Laser-activated nanothermolysis of cells

Research paper thumbnail of High contrast optoacoustical imaging using nanoparticles

Research paper thumbnail of XeCl laser-induced fluorescence detection of peroxidized lipoproteins in lipid-rich atherosclerotic lesions

Laser-induced fluorescence spectroscopy of arterial surfaces provides information about the compo... more Laser-induced fluorescence spectroscopy of arterial surfaces provides information about the composition of atherosclerotic plaques. The aim of the study was to determine whether accumulation of peroxidized lipoproteins in arterial walls, a process postulated to play a role in initiating atherosclerotic changes, can be demonstrated by fluorescence spectroscopy. XeCl excimer laser ((lambda) equals 308 nm) induced fluorescence of human aortas containing early lipid-rich, non-collagenous lesions exhibited marked red shifts and broadening of the fluorescence spectra compared with spectra from non-atherosclerotic aortas. Similar profiles were observed in spectra obtained from oxidatively modified LDL, but not native LDL. In hypercholesterolemic rabbits with early foam cell lesions, spectral shifts resembled those of oxidized (beta) -VLDL, the major lipoprotein accumulating in arteries of rabbits fed cholesterol. XeCl laser-fluorescence spectroscopy of arterial surfaces may be useful for the identification of arterial plaques indicative of atherosclerosis in its early and probably reversible stages.

Research paper thumbnail of Laser optic-acoustic tomography for medical diagnostics: principles

This paper is to describe principles of laser optoacoustic tomography for medical diagnostics. Tw... more This paper is to describe principles of laser optoacoustic tomography for medical diagnostics. Two types of imaging modes are presented. The first is the tomography in transmission mode, which utilizes detection of stress transients transmitted from the laser-excited volume toward the depth through thick layers of tissue. The second is the tomography in reflection mode which utilizes detection of stress transients generated in superficial tissue layer and reflected back toward tissue surface. To distinguish the two modes, we have abbreviated them as (1) laser optoacoustic tomography in transmission mode, LOATT, and (2) time-resolved stress detection tomography of light absorption, TRSDTLA, in reflection mode where emphasis is made on high spatial resolution of images. The basis for laser optoacoustic tomography is the time-resolved detection of laser-induced transient stress waves, selectively generated in absorbing tissues of diagnostic interest. Such a technique allows one to visualize absorbed light distribution in turbid biological tissues irradiated by short laser pulses. Laser optoacoustic tomography can be used for detection of tissue pathological changes that result in either increased concentration of various tissue chromophores such as hemoglobin or in development of enhanced microcirculation in diseased tissue. Potential areas of applications are diagnosis of cancer, brain hemorrhages, arterial atherosclerotic plaques, and other diseased tissues. In addition, it can provide feedback information during medical treatments. Both LOATT and TRSDTLA utilize laser excitation of biological tissues and sensitive detection of laser-induced stress waves. Optical selectivity is based upon differences in optical properties of pathologically different tissues. Sensitivity comes from stress generation under irradiation conditions of temporal stress confinement. The use of sensitive wide-band lithium niobate acoustic transducers expands limits of laser optoacoustic tomography. The technology allows us to determine directly temperature distributions in tissues and locate tissues volumes with different absorption. To demonstrate principles of TRSDTLA, experiments were conducted in vivo with mice-model for breast cancer using specially designed front-surface transducers- reflectometers. To present advantages and limitation of LOATT, experiments were performed in phantoms made of gel with polystyrene spheres colored with copper sulfate. Our experimental results and theoretical calculations show that TRSDTLA can be applied for non- invasive histology of layered tissues with in-depth resolution of up to 2 microns. TRSDTLA in acoustic reflection mode is promising for diagnostics of skin and ocular diseases. LOATT in acoustic transmission mode can be applied for detection of small tissue volumes with enhanced absorption located inside organs at the depth of up to 10 cm.

Research paper thumbnail of Two-quantum UV photolysis of nucleic acid components in aqueous solution in comparison with γ-radiolysis

Research paper thumbnail of LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: On a plasmon resonance in ellipsoidal nanoparticles

The dependence of the plasmon resonance frequency of metal ellipsoids of revolution on their ecce... more The dependence of the plasmon resonance frequency of metal ellipsoids of revolution on their eccentricity is calculated. The plasmon resonance shifts to the red with increasing eccentricity and its intensity increases. The resonance intensity increases with decreasing the imaginary part of the dielectric constant of a metal. The plasmon resonance frequency in a suspension of randomly oriented prolate nanoparticles (with a large eccentricity) almost exactly coincides with that in a suspension of oriented particles. These features permit the efficient improvement of the sensitivity and resolving power of optoacoustic tomography by introducing prolate metal nanoparticles into the region of an object under study. The possibility of plasmon resonance narrowing by introducing metal nanoparticles into an amplifying medium is pointed out.

Research paper thumbnail of Three-dimensional acousto-optic mapping using planar scanning with ultrasound bursts

Proceedings of SPIE - The International Society for Optical Engineering

We have investigated the application of AO sensing for quantitative three-dimensional mapping of ... more We have investigated the application of AO sensing for quantitative three-dimensional mapping of tissue-mimicking phantoms. An Intralipid phantom, which contains a turbid absorber, confined in a silicone tube, was used. Multiply scattered pulsed laser light was modulated by ultrasonic bursts focused in a predefined volume in the medium. By varying the delay time between ultrasound burst initiation and light pulse firing we could perform a scan in the ultrasound-propagation plane. By moving the ultrasound transducer, we could build up a volumetric map of modulation depth values. We have experimentally determined the acousto-optical modulation depth as a function of the absorption coefficient in phantom voxels of a few millimeters in size.

Research paper thumbnail of Optoacoustic monitoring of drug and contrast agent diffusion through skid

Biomedical Optical Spectroscopy and Diagnostics, 2000

ABSTRACT

Research paper thumbnail of Method of laser activated nano-thermolysis for elimination of tumor cells

Cancer Letters, 2006

We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activ... more We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activated Nanothermolysis and propose this method for purging of bone marrow and blood transplants. K562 and human lympholeukemia cells were eliminated in experiments by laser-induced micro-bubbles that emerge inside individual target cells around selectively formed clusters of light-absorbing gold nanoparticles. Pretreatment of tumor cells with specific monoclonal antibodies and Igconjugated 30-nm gold particles allowed the formation of clusters of 10-20 on the surface of cell membrane. Electron microscopy found the nanoparticulate clusters inside the cells. Total (100%) elimination of K562 cells targeted with specific antibodies was achieved with single laser pulses with optical fluence of 5 J/cm 2 at the wavelength of 532 nm without damage to the same cells targeted without specific antibodies. Total elimination of human lymphoblasts from suspension of normal stem cells was achieved by a single laser pulse with the optical fluence of 1.7 J/cm 2 , while the damage level of normal cells was 16%. q

Research paper thumbnail of Lantcet: Novel laser nanotechnology for graft purging

Biology of Blood and Marrow Transplantation, 2006

We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activ... more We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activated Nanothermolysis and propose this method for purging of bone marrow and blood transplants. K562 and human lympholeukemia cells were eliminated in experiments by laser-induced micro-bubbles that emerge inside individual target cells around selectively formed clusters of light-absorbing gold nanoparticles. Pretreatment of tumor cells with specific monoclonal antibodies and Igconjugated 30-nm gold particles allowed the formation of clusters of 10-20 on the surface of cell membrane. Electron microscopy found the nanoparticulate clusters inside the cells. Total (100%) elimination of K562 cells targeted with specific antibodies was achieved with single laser pulses with optical fluence of 5 J/cm 2 at the wavelength of 532 nm without damage to the same cells targeted without specific antibodies. Total elimination of human lymphoblasts from suspension of normal stem cells was achieved by a single laser pulse with the optical fluence of 1.7 J/cm 2 , while the damage level of normal cells was 16%. q

Research paper thumbnail of Optoacoustic microscopy using laser beam deflection technique

Photons Plus Ultrasound: Imaging and Sensing 2014, 2014

ABSTRACT Optoacoustic microscopy (OAM) is an emerging technology combining the beneficial feature... more ABSTRACT Optoacoustic microscopy (OAM) is an emerging technology combining the beneficial features of optical contrast and ultrasound resolution, to form a hybrid imaging technique capable of multi-scale, high-contrast and high-resolution imaging through optically scattering biological tissues. In the past 15 years, two system modifications have been developed for optoacoustic / photoacoustic microscopy: acoustic-resolution AR-OAM and optical-resolution OR-OAM. Typically, acoustic resolution systems can image deeper tissues structures, however, with resolution at least an order of magnitude worse than the systems of optical-resolution. It would be attractive for variety of biomedical applications to attain high (submicron) resolution at a depth exceeding the present limit of the optical resolution optoacoustic microscopy. Here we introduce a novel, all-optical method for OAM, in which not only thermal energy deposition, but also optoacoustic signal detection is achieved optically. In our design the probe laser beam was used as an ultrawide-band ultrasonic transducer. In this method the acoustic pressure wave amplitude is proportional to the angle of deflection of the probing CW laser beam incident on a balanced dual photodiode. Such laser beam deflection (LBD) method overcomes the limitations of conventional piezoelectric ultrasound transducers and optical interferometers. LBD method allows one to use high numerical aperture objectives for better focusing, avoid distortions associated with the system elements that separate optical and acoustic paths, and provides better sensitivity than any optical interferometer. It also provides a non-contact method that is insensitive to optical and acoustic artifacts typical of backward mode of optoacoustic imaging. The LBD sensitivity depends on a large number of system parameters such as probe beam power, spot size, interaction length, optical refraction index of the coupling medium, laser wavelength, photodiode sensitivity, proximity to the optoacoustic source, and thus, can be optimized. The basic setup of OR-LBD-OAM shows high sensitivity competitive with commercial ultrasonic transducers. We report first images of biological cells and tissues obtained using this technique.

Research paper thumbnail of <title>Optoacoustic imaging system with improved collection efficiency</title>

Photons Plus Ultrasound: Imaging and Sensing 2011, 2011

We introduce a novel experimental design for non-invasive scanning optoacoustic microscopy that u... more We introduce a novel experimental design for non-invasive scanning optoacoustic microscopy that utilizes a parabolic surface for ultrasound focusing. We demonstrate that off-axis parabolic mirrors made of sufficiently high acoustic impedance materials work as ideal reflectors in a wide range of apertures and provide lossless conversion of a spherical acoustic wavefront into a plane wave. We further test the performance of a custom optoacoustic imaging setup which was developed and built based on these principles. The achieved resolution limit of 0.3 mm, with NA of 0.5 and the transducer bandwidth of 5 MHz, matches the resolution limit defined by diffraction. Although further improvements of current experimental setup are required to achieve resolution similar to leading microscopy systems, this proof-ofconcept work demonstrates the viability of the proposed design for optoacoustic microscopy applications.

Research paper thumbnail of Highly purified biocompatible gold nanorods for contrasted optoacoustic imaging of small animal models

Nanoscience and nanotechnology letters (Print), 2012

We developed a methodology for high yield synthesis of gold nanorods (GNR) with narrow band optic... more We developed a methodology for high yield synthesis of gold nanorods (GNR) with narrow band optical absorption centered at 760 nm. GNR were purified from hexadecyltrimethylammonium bromide (CTAB) and coated with polyethylene glycol (PEG). The molar ratio between GNR and PEG (1÷50000) was optimized to make the conjugate a biocompatible PEG-GNR contrast agent for optoacoustic (OA) imaging. In vitro toxicity studies showed no significant change in survival rates of cultured normal (IEC-6, MDCK) and cancer (SKBR3 and HEPG2) cells after they were incubated with 0.125 to 1.25 nM PEG-GNR solutions. In vivo toxicity studies in nude mice showed no pathological changes in liver after the IV injection of GNR. Significant enhancements of OA contrast in comparison to images of untreated mice were observed 1 hour after the GNR injection in a dose of 20 mg gold per kg of body mass.

Research paper thumbnail of 3D laser optoacoustic ultrasonic imaging system for research in mice (LOUIS-3DM)

Photons Plus Ultrasound: Imaging and Sensing 2014, 2014

ABSTRACT In this work we introduce an improved prototype of three-dimensional imaging system that... more ABSTRACT In this work we introduce an improved prototype of three-dimensional imaging system that combines optoacoustic tomography (OAT) and laser ultrasound tomography (LUT) to obtain coregistered maps of tissue optical absorption and speed of sound (SoS). The OAT scan is performed by a 360 degree rotation of a mouse with respect to an arc-shaped array of ultrasonic transducers. A Q-switched laser system is used to establish optoacoustic illumination pattern appropriate for deep tissue imaging with a tunable (730-840 nm) output wavelengths operated at 10 Hz pulse repetition rate. A 532 nm wavelength output, being mostly absorbed within a narrow superficial layer of skin, is used to outline the visualized biological object. Broadband laser ultrasound emitters are arranged in another arc pattern and are positioned opposite and orthogonal to the array of transducers. This imaging geometry allows reconstruction of volumes that depict SoS distributions from the measured time of flight data. The reconstructed LUT images can subsequently be employed by an optoacoustic reconstruction algorithm to compensate for acoustic wavefield aberration and thereby improve accuracy of the reconstructed images of the absorbed optical energy. The coregistered OAT-LUT imaging is validated in a phantom and live mouse using a single-slice system prototype.

Research paper thumbnail of Biomedical optoacoustics(San Jose CA, 25-27 January 2000)

Research paper thumbnail of Biomedical optoacoustics IV(San Jose CA, 26-27 January 2003)

Research paper thumbnail of Optoacoustic systems for functional and molecular imaging in clinical and preclinical research

2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009

ABSTRACT Optoacoustic imaging systems provide a unique opportunity to visualize, with high spatia... more ABSTRACT Optoacoustic imaging systems provide a unique opportunity to visualize, with high spatial resolution, the distribution of optical energy in opaque biological tissues and even to visualize the distribution of optically absorbing molecules in tissues. Since hemoglobin of blood is the main tissue chromophore that dominates optical absorption in the near-infrared spectral range, the optoacoustic imaging is well suitable for visualization of blood distributions associated with various diseases, such as cancer and atherosclerosis. Design of optoacoustic systems for two-dimensional and three-dimensional imaging and their applications in clinical and preclinical oncology will be presented.

Research paper thumbnail of Future Biomedical Applications of Optoacoustic Tomography

Research paper thumbnail of 3D Optoacoustic Tomography: From Molecular Targets in Mouse Models to Functional Imaging of Breast Cancer

Research paper thumbnail of High contrast optoacoustical imaging using non-spherical nanoparticles

Research paper thumbnail of Laser-activated nanothermolysis of cells

Research paper thumbnail of High contrast optoacoustical imaging using nanoparticles

Research paper thumbnail of XeCl laser-induced fluorescence detection of peroxidized lipoproteins in lipid-rich atherosclerotic lesions

Laser-induced fluorescence spectroscopy of arterial surfaces provides information about the compo... more Laser-induced fluorescence spectroscopy of arterial surfaces provides information about the composition of atherosclerotic plaques. The aim of the study was to determine whether accumulation of peroxidized lipoproteins in arterial walls, a process postulated to play a role in initiating atherosclerotic changes, can be demonstrated by fluorescence spectroscopy. XeCl excimer laser ((lambda) equals 308 nm) induced fluorescence of human aortas containing early lipid-rich, non-collagenous lesions exhibited marked red shifts and broadening of the fluorescence spectra compared with spectra from non-atherosclerotic aortas. Similar profiles were observed in spectra obtained from oxidatively modified LDL, but not native LDL. In hypercholesterolemic rabbits with early foam cell lesions, spectral shifts resembled those of oxidized (beta) -VLDL, the major lipoprotein accumulating in arteries of rabbits fed cholesterol. XeCl laser-fluorescence spectroscopy of arterial surfaces may be useful for the identification of arterial plaques indicative of atherosclerosis in its early and probably reversible stages.

Research paper thumbnail of Laser optic-acoustic tomography for medical diagnostics: principles

This paper is to describe principles of laser optoacoustic tomography for medical diagnostics. Tw... more This paper is to describe principles of laser optoacoustic tomography for medical diagnostics. Two types of imaging modes are presented. The first is the tomography in transmission mode, which utilizes detection of stress transients transmitted from the laser-excited volume toward the depth through thick layers of tissue. The second is the tomography in reflection mode which utilizes detection of stress transients generated in superficial tissue layer and reflected back toward tissue surface. To distinguish the two modes, we have abbreviated them as (1) laser optoacoustic tomography in transmission mode, LOATT, and (2) time-resolved stress detection tomography of light absorption, TRSDTLA, in reflection mode where emphasis is made on high spatial resolution of images. The basis for laser optoacoustic tomography is the time-resolved detection of laser-induced transient stress waves, selectively generated in absorbing tissues of diagnostic interest. Such a technique allows one to visualize absorbed light distribution in turbid biological tissues irradiated by short laser pulses. Laser optoacoustic tomography can be used for detection of tissue pathological changes that result in either increased concentration of various tissue chromophores such as hemoglobin or in development of enhanced microcirculation in diseased tissue. Potential areas of applications are diagnosis of cancer, brain hemorrhages, arterial atherosclerotic plaques, and other diseased tissues. In addition, it can provide feedback information during medical treatments. Both LOATT and TRSDTLA utilize laser excitation of biological tissues and sensitive detection of laser-induced stress waves. Optical selectivity is based upon differences in optical properties of pathologically different tissues. Sensitivity comes from stress generation under irradiation conditions of temporal stress confinement. The use of sensitive wide-band lithium niobate acoustic transducers expands limits of laser optoacoustic tomography. The technology allows us to determine directly temperature distributions in tissues and locate tissues volumes with different absorption. To demonstrate principles of TRSDTLA, experiments were conducted in vivo with mice-model for breast cancer using specially designed front-surface transducers- reflectometers. To present advantages and limitation of LOATT, experiments were performed in phantoms made of gel with polystyrene spheres colored with copper sulfate. Our experimental results and theoretical calculations show that TRSDTLA can be applied for non- invasive histology of layered tissues with in-depth resolution of up to 2 microns. TRSDTLA in acoustic reflection mode is promising for diagnostics of skin and ocular diseases. LOATT in acoustic transmission mode can be applied for detection of small tissue volumes with enhanced absorption located inside organs at the depth of up to 10 cm.

Research paper thumbnail of Two-quantum UV photolysis of nucleic acid components in aqueous solution in comparison with γ-radiolysis

Research paper thumbnail of LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: On a plasmon resonance in ellipsoidal nanoparticles

The dependence of the plasmon resonance frequency of metal ellipsoids of revolution on their ecce... more The dependence of the plasmon resonance frequency of metal ellipsoids of revolution on their eccentricity is calculated. The plasmon resonance shifts to the red with increasing eccentricity and its intensity increases. The resonance intensity increases with decreasing the imaginary part of the dielectric constant of a metal. The plasmon resonance frequency in a suspension of randomly oriented prolate nanoparticles (with a large eccentricity) almost exactly coincides with that in a suspension of oriented particles. These features permit the efficient improvement of the sensitivity and resolving power of optoacoustic tomography by introducing prolate metal nanoparticles into the region of an object under study. The possibility of plasmon resonance narrowing by introducing metal nanoparticles into an amplifying medium is pointed out.

Research paper thumbnail of Three-dimensional acousto-optic mapping using planar scanning with ultrasound bursts

Proceedings of SPIE - The International Society for Optical Engineering

We have investigated the application of AO sensing for quantitative three-dimensional mapping of ... more We have investigated the application of AO sensing for quantitative three-dimensional mapping of tissue-mimicking phantoms. An Intralipid phantom, which contains a turbid absorber, confined in a silicone tube, was used. Multiply scattered pulsed laser light was modulated by ultrasonic bursts focused in a predefined volume in the medium. By varying the delay time between ultrasound burst initiation and light pulse firing we could perform a scan in the ultrasound-propagation plane. By moving the ultrasound transducer, we could build up a volumetric map of modulation depth values. We have experimentally determined the acousto-optical modulation depth as a function of the absorption coefficient in phantom voxels of a few millimeters in size.

Research paper thumbnail of Optoacoustic monitoring of drug and contrast agent diffusion through skid

Biomedical Optical Spectroscopy and Diagnostics, 2000

ABSTRACT

Research paper thumbnail of Measurement of Optical Fluence Distribution and Optical Properties of Tissues Using Time-Resolved Profiles of Optoacoustic Pressure

Spatial profiles of the optical fluence distribution in live tissues can be used for noninvasive ... more Spatial profiles of the optical fluence distribution in live tissues can be used for noninvasive measurements of tissue optical properties. Axial profiles of the optical fluence distribution can be, in turn, measured from the spatial profiles of the laser induced optoacoustic pressure. Short (nansecond) laser pulses and ultrawideband ultrasonic transducers enable these measurements.