Alexander Oraevsky

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.

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.

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.

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.

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.

In `5'-translational blockage,' significantly reduced yields of proteins are synthesized in Escherichia coli when consecutive low-usage codons are inserted near translation starts of messages (with reduced or no effect when these same codons are inserted downstream). We tested the hypothesis that ribosomes encountering these low-usage codons prematurely release the mRNA. RNA from polysome gradients was fractionated into pools of polysomes, monosomes and ribosomes-free. New hybridization probes, called `molecular beacons,' and standard slot-blots, were used to detect test messages containing either consecutive low-usage AGG (arginine) or synonymous high-usage CGU insertions near the 5' end. The results show an approximately twofold increase in the ratio of free to bound mRNA when the low-usage codons were present compared to high-usage codons. In contrast, there was no difference in the ratio of free to bound mRNA when consecutive low-usage CUA or high-usage CUG (leuc...

Trabeculectomy with early postoperative slit lamp laser suture lysis is a controlled means of maximizing bleb filtration and reducing intraocular pressure. However, this procedure is not possible in children and even some adults. Thus, an effective alternative method for postoperative laser suture lysis was investigated. Dissection of 15 scleral flaps was performed on two human cadaver eyes. Each flap was closed with two 10-0 nylon sutures and the conjunctiva repositioned to cover the sutures. Laser suture lysis was performed using an optical fiber probe for the Argon/Dye laser and a Hoskins laser lens. Five different wavelengths were studied: red (630 nm), orange (595 nm), yellow (577 nm), blue-green (488 - 514 nm), and green (514 nm). Each individual wavelength was studied using six scleral flap sutures, and a single laser application was applied to each suture. Suture lysis was attainable with each wavelength, however the argon green lysed 100 percent of the sutures. Histologic a...

ABSTRACT Optoacoustic tomography (OAT) is an emerging ultrasound-mediated biophotonic imaging modality that has exciting potential for many biomedical imaging applications. There is great interest in conducting B-mode ultrasound and OAT imaging studies for breast cancer detection using a common transducer. In this situation, the range of tomographic view angles is limited, which can result in distortions in the reconstructed OAT image if conventional reconstruction algorithms are applied to limited-view measurement data. In this work, we investigate an image reconstruction method that utilizes information regarding target boundaries to improve the quality of the reconstructed OAT images. This is accomplished by developing boundary-constrained image reconstruction algorithm for OAT based on Bayesian image reconstruction theory. The computer-simulation studies demonstrate that the Bayesian approach can effectively reduce the artifact and noise levels and preserve the edges in reconstructed limited-view OAT images as compared to those produced by a conventional OAT reconstruction algorithm.

The effects of an inappropriately chosen speed-of-sound in photoacoustic imaging reconstructions are to cause blurring of images and impairment of contrast. Here we outline a new methodology to measure the speed-of-sound in a photoacoustic imager with little or no additional cost and without the need to perform extra measurements. The method uses a strong absorber of light which is placed

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, mueff by exponential fitting of the time-resolved optoacoustic profiles. Glucose

Nanoparticles and molecular chromophores with strong optical absorption in the near-infrared spectral range can be used as contrast agents for optoacoustic (photoacoustic) imaging, thereby significantly enhancing sensitivity and enabling new applications of this novel and rapidly growing biomedical imaging technology.

A new method for reconstruction of optoacoustic images is proposed. The method of image reconstruction incorporates multiresolution wavelet filtering into spherical back-projection algorithm. According to our method, each optoacoustic signal detected with an array of ultrawide-band transducers is decomposed into a set of self-similar wavelets with different resolution (characteristic frequency) and then back-projected along the spherical traces for each resolution

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.