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In this report, we demonstrate the feasibility of using optoacoustic tomography (OAT) to evaluate biodistributions of nanoparticles in animal models. The redistribution of single-walled carbon nanotubes (SWCNTs) was visualized in living mice. Nanoparticle concentrations in harvested organs were measured spectroscopically using the intrinsic optical absorption and fluorescence of SWCNTs. Observed increases in optoacoustic signal brightness in tissues were compared with increases in optical absorption coefficients caused by SWCNT accumulation. The methodology presented in this report can further be extended to calibrate the sensitivity of an optoacoustic imaging system for a range of changes in optical absorption coefficient values at specific locations or organs in a mouse body to enable noninvasive measurements of nanoparticle concentrations in vivo. Additionally, qualitative information provided by OAT and quantitative information obtained ex vivo may provide valuable feedback for advancing methods of quantitative analysis with OAT.

Background and Objective Previously reported studies on laser nano-thermolysis of cancerous cells demonstrated insufficient efficacy and specificity of malignant cell damage. Safety, that is, absence of damage to normal cells in the course of the laser thermolysis was also low due to less than optimal protocol of cancer cell targeting with nanoparticles (NP). The objective of this study was two-fold: to optimize NP targeting to real tumor (human) cells and to better understand physical mechanisms of cell damage for improved control of the laser ablation. Study Design/Materials and Methods We have suggested (1) two-stage targeting method to form clusters of light-absorbing gold NPs selectively in target cells, and (2) the cell damage mechanism through laser-induced generation of vapor bubbles around NP clusters. Experimental investigation of laser nano-thermolysis of leukemia cells was performed using 30 nm spherical gold nanoparticles as a light absorbing agent, and photothermal and fluorescent microscopies as well as flow cytometry as methods to monitor microbubble formation and resulting damage of leukemia cells in human bone marrow specimens. Results NP clusters were formed and visualized using fluorescence microscopy at cell membranes and in cytoplasm of B-lymphoblasts. Laser irradiation of cells (532 nm, 10 nanoseconds, 0.6 J/cm2) induced microbubbles selectively in leukemia cells with large clusters, but not in cells with single NPs or small clusters. Quantitative analysis demonstrated that only 0.1%–1.5% of tumor cells and 77%–84% of normal bone marrow cells survived laser pulse. Conclusions Two-stage cell targeting method permits formation of NP clusters selectively in diagnosis-specific tumor cells. The clusters serve as effective sources of photothermally-induced microbubbles, which kill individual target cells after a single laser pulse. The laser fluence threshold for generation of microbubbles is inversely proportional to the volume of NP clusters. Lasers Surg. Med. 38:631–642, 2006. © 2006 Wiley-Liss, Inc.

Background and Objectiue: It is desirable for laser microsurgical procedures to remove tissue accurately and with minimal thermal and mechanical damage to adjacent non-irradiated tissues. Pulsed laser ablation can potentially remove biological tissue with microprecision if appropriate irradiation conditions are applied. The major goal of this study was to determine whether laser ablation is possible at temperatures below 100°C. Another aim was to test thermoelastic and recoil stress magnitudes and to estimate their effects on phantom and biological tissue. Study DesignlMateriaZs and Methods: Pulsed laser ablation of water (aqueous solution of potassium chromate) and water containing soft tissues (collagen gel and pig liver) irradiated under confined stress conditions was studied. The ablation mechanism and stages of the ablation process were determined based on time-resolved measurements of laser-induced acoustic waves with simultaneous imaging of the ablation process by laser-flash photography. Results: This study reveals the important role of tensile thermoelastic stress, which produces efficient cavitation that drives material ejection at temperatures substantially below 100°C. Ablation thresholds for the aqueous solution, collagen gel, and liver were 20,38, and 55 J/cm”, respectively, which correspond to temperature jumps of 5,10, and 15°C. Two distinct stages of material ejection were observed: (1) initial removal of small volumes of material due to the rupture of single subsurface bubbles, (2) bulk material ablation in the form of jets produced by intense hydrodynamic motions formed upon collapse of large bubbles after coalescence of smaller bubbles. The duration of material ejection upon short-pulse ablation may vary from microseconds to submilliseconds, and depended on the mechanical properties of materials and the incident laser fluence. ConcZusion: Nanosecond laser ablation of water, gels, and soft tissue under confined-stress conditions of irradiation may occur at temperatures below 100°C. This ablation regime minimizes thermal injury to adjacent tissues and involves thermoelastic stress and recoil pressure magnitudes, which may be tolerated by tissues adjacent to an ablated crater. Q 1996 Wiley-Liss, Inc.

XeCl laser ablation of atherosclerotic aorta tissue was investigated. Luminescence spectra of ablation products were measured for soft and hard arterial tissues. A pronounced difference observed between plume luminescence for various plaques and normal vessel wall correlates with the chemical composition of the tissue. The mechanism of plume luminescence appeared to be thermochemical excitation of ablation products (particles, atoms, molecules, etc.) in the air. The process of soft tissue ablation was delayed with respect to the exciting laser pulse at relatively low laser fluences close to the ablation threshold. The kinetics of the ablation process as a function of laser-pulse energy fluence is reported. The data indicate that tissue ejection mechanism, which involves vapor bubbles formation, expansion and explosion, is suitable for the description of the XeCl excimer laser ablation of soft tissues. © 1993 Wiley-Liss, Inc.

Quantitative studies are conducted into the absolute pressure values of the acoustical and shock waves generated and propagating in a biotissue under pulsed (tau p = 50 ns) UV (lambda = 308 nm) laser irradiation (below and above the ablation threshold). Powerful (several hundreds of bars in pressure) high-frequency (f approximately 10(7) Hz) acoustic compression and rarefaction pulses are found to be generated in the biotissue. The amplitudes and profiles of the acoustic pulses developing in atherosclerotic human aorta tissues and an aqueous CuCl2 solution under laser irradiation are investigated as a function of the laser pulse energy fluence. The results obtained point to the absence of the cold spallation of the objects of study by rarefaction waves. Based on experimental data, the rise rates, pressure gradients, and propagation velocities of shock waves in the biotissue are calculated. The experimental data are found to agree well with the theoretical estimates.

The energetics of 308-nm excimer laser irradiation of human aorta were studied. The heat generation that occurred during laser irradiation of atherosclerotic aorta equaled the absorbed laser energy minus the fraction of energy for escaping fluorescence (0.8-1.6%) and photochemical decomposition (2%). The absorbed laser energy is equal to the total delivered light energy minus the energy lost as specular reflectance (2.4%, air/tissue) and diffuse reflectance (11.5-15.5%). Overall, about 79-83.5% of the delivered light energy was converted to heat. We conclude that the mechanism of XeCl laser ablation of soft tissue involves thermal overheating of the irradiated volume with subsequent explosive vaporization. The optical properties of normal wall of human aorta and fibrous plaque, both native and denatured were determined. The light scattering was significant and sufficient to cause a subsurface fluence (J/cm2) in native aorta that equaled 1.8 times the broad-beam radiant exposure, phi o (2.7 phi o for denatured aorta). An optical fiber must have a diameter of at least 800 microns to achieve a maximum light penetration (approximately 200 microns for phi o/e) in the aorta along the central axis of the beam.

Purpose: Optoacoustic tomography (OAT) is inherently a three-dimensional (3D) inverse problem. However, most studies of OAT image reconstruction still employ two-dimensional (2D) imaging models. One important reason is because 3D image reconstruction is computationally burdensome. The aim of this work is to accelerate existing image reconstruction algorithms for 3D OAT by use of parallel programming techniques. Methods: Parallelization strategies are proposed to accelerate a filtered backprojection (FBP) algorithm and two different pairs of projection/backprojection operations that correspond to two different numerical imaging models. The algorithms are designed to fully exploit the parallel computing power of graphic processing units (GPUs). In order to evaluate the parallelization strategies for the projection/backprojection pairs, an iterative image reconstruction algorithm is implemented. Computer-simulation and experimental studies are conducted to investigate the computational efficiency and numerical accuracy of the developed algorithms. Results: The GPU implementations improve the computational efficiency by factors of 1, 000, 125, and 250 for the FBP algorithm and the two pairs of projection/backprojection operators, respectively. Accurate images are reconstructed by use of the FBP and iterative image reconstruction algorithms from both computer-simulated and experimental data. Conclusions: Parallelization strategies for 3D OAT image reconstruction are proposed for the first time. These GPU-based implementations significantly reduce the computational time for 3D image reconstruction, complementing our earlier work on 3D OAT iterative image reconstruction.

The efficiency of RNA-protein crosslink and RNA chain break formation under nanosecond or picosecond UV-laser pulse irradiation of tobacco mosaic virus was determined. It was found that on high-intensity UV-laser irradiation the quantum yields of both reactions increase considerably as compared to the usual (low-intensity) UV-irradiation. The RNA-protein crosslink quantum yield was found to be 1.8 x 10(-5) and 1.2 x 10(-4) and that of RNA chain breaks 1.7 x 10(-4) and 8.9 x 10(-4) for nanosecond and picosecond irradiation, respectively.