Treatment of solid cancers by photodynamic therapy (PDT) triggers a strong acute inflammatory reaction localized to the illuminated malignant tissue. This event is regulated by a massive release of various potent mediators which have a profound effect not only on local host cell populations, but also attract different types of immune cells to the treated tumor. Phagocytosis of PDT-damaged cancerous cells by antigen presenting cells, such as activated tumor associated macrophages, enables the recognition of even poorly immunogenic tumors by specific immune effector cells and the generation of immune memory populations. Because of its inflammatory/immune character, PDT is exceptionally responsive to adjuvant treatments with various types of immunotherapy. Combining PDT with immuneactivators, such as cytokines or other specific or non-specific immune agents, rendered marked improvements in tumor cures with various cancer models. Another clinically attractive strategy is adoptive immunotherapy, and the prospects of its use in conjunction with PDT are outlined.

Photodynamic therapy (PDT) of cancer is based on the systemic administration of photosensitive drugs followed by exposure of the tumor mass to light of particular wavelength. The combination of drug uptake in malignant tissues and selective delivery of laser-generated light provides for an effective therapy with efficient tumor cytotoxicity and minimal normal tissue damage. There are various studies on the effect of photoactivated photosensitizers on host immune response in tumor bearing mice. Since immunity is important in the control of tumor growth and spreading in our laboratory we examine the effect of PDT on immune compartment. Spleen hyperplasia as well as spleen and marrow hypercellularities were observed in tumor bearing mice treated with Aluminum Disulfonated Phthalocyanine (AlS₂Pc) and laser light. Phytohaemagglutinin (T lymphocytes mitogen) and Lypolisaccaride (B lymphocytes mitogen), stimulation of spleen lymphocytes caused an increase in blast transformation in tumor bearing mice. Furthermore splenocytes and macrophages collected from mice treated with PDT were cytotoxic in vivo (Winn Assay) parental against tumor cells. The results observed suggest that PDT is able to modulate the immune response and oncological patients treated with PDT could become immune versus a relapse or versus the minimal residual disease.

Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response which potentiates anti-tumor immunity, but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood, but are likely to involve meditation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10. IL-6 mRNA and protein are rapidly and strongly enhanced in the PDT treated EMT6 tumor. Previous studies have shown that intratumoral injection of IL- 6 or transduction of the IL-6 gene into tumor cells can enhance tumor immunogenicity and inhibit tumor growth in experimental murine tumor systems. Thus, PDT may enhance local anti-tumor immunity by up-regulating IL-6. PDT also results in an increase in IL-10 mRNA and protein in the skin. The same PDT regime which enhances IL-10 production in the skin has been shown to strongly inhibit the CHS response. The kinetics of IL-10 expression coincide with the known kinetics of PDT induced CHS suppression and we propose that the enhanced IL-10 expression plays a role in the observed suppression of cell mediated responses seen following PDT.

A new laser immunotherapy was used to treat metastatic mammary rat tumors. This new modality consists of three components: a near-infrared diode laser, a photosensitizer, and an immunoadjuvant. The sensitizer-adjuvant solution was injected directly to the tumor, followed by a non-invasive laser application. The new method resulted in total eradication of the treated primary tumors and eradication of untreated metastases at remote sites. Observed was the long-term survival of treated tumor-bearing rats: up to 120 days after tumor inoculation, a 300% increase in survival length compared with untreated control tumor-bearing rats. In addition, the successfully treated rats were refractory to tumor rechallenge with 10 times of the original tumor dose. Fluorescein and peroxidase immunochemical assays were also performed using sera from cured rats as the primary antibody. Strong antibody binding to both live and preserved tumor cells was observed. Western blot analysis, using the cured rat serum as primary antibody also showed distinctive protein binding, suggesting the induction of tumor-specific humoral immune response. These results indicated that an immune response was induced by the treatment of laser, photosensitizer and immunoadjuvant.

Laser immunotherapy, using a combination of 805 nm diode laser, photosensitizer indocyanine green and immunoadjuvant glycated chitosan, has shown an induced anti-tumor immune response in treatment of metastatic rat tumors. In additional to an apparent systemic, long-term humoral immunological reaction, there could also be laser induced local cellular immune responses. A morphological study was performed to study the immune cells and their infiltration to tumor tissue after this laser immunotherapy treatment. Tumor-bearing rats were terminated at designated times after the treatment; both the tumor and the surrounding normal tissue were collected. The tissue samples were observed under electron microscope. The number and types of infiltrating cells at the tumor site were studied after treatment to determine the contribution of these cells in the elimination of tumors. The tumor cell structural changes resulted from laser-tissue photothermal interaction was investigated. The morphology of tumor development and activities of immune cells including both lymphocytes and plasma cells could shed light on the mode of action of laser treatment of tumors.

We investigated the photovasorelaxation with intravascular transluminal irradiation using in vivo model. A 2.5 Fr. catheter was inserted in the femoral artery of a rabbit under anesthesia. A 400 micrometers diameter quartz fiber was inserted through the catheter. The catheter was withdrawn from the distal end to the proximal end of the exposed femoral artery without laser irradiation in order to observe the mechanical dilation by the procedure. The femoral artery lumen was irradiated by a Helium-Cadmium(He-Cd) laser (wavelength; 325 nm) with 8 mW through the fiber during 30 s. We carried out that the laser irradiation produced vasorelaxation (185% on the average) compared with mechanical vasodilation (150% on the average) with angiography. The results suggest that intravascular transluminal irradiation with low-power UV laser might be applicable to the relief of acute arterial vasospasm.

The cellular pigments of the retinal pigment epithelium are photoactive; that is, they promote free radical oxidative reactions when illuminated with visible or ultraviolet light. This activity is sufficient to cause photo-oxidation of several major cellular components such as antioxidants, dinucleotide cofactors, proteins and fatty acids. The present investigation determined the relative ability of melanin, lipofuscin, and melanolipofuscin granules isolated from human and bovine eyes to oxidize linoleic and docosahexaenoic acids, which are polyunsaturated fatty acids. The dark reactivity as well as the light-stimulated reactions were determined. All RPE pigment granules stimulated fatty acid oxidation when irradiated with the blue-green (488.1 and 514.5 nm) emission of the Argon-ion laser. Only lipofuscin, however, caused peroxidation of fatty acids in the dark. These findings not only suggest that accumulation of lipofuscin in the aging eye may contribute to increased photo-oxidative stress to the retina and RPE, but also that the photoactive RPE pigments might serve as endogenous photosensitizers for therapeutic applications.

We develop a theoretical model to calculate the temperature field and the size of modified structure area in cartilaginous tissue. The model incorporates both thermal and mass transfer in a tissue regarding bulk absorption of laser radiation, water evaporation from a surface and temperature dependence of diffusion coefficient. It is proposed that due to bound- to free-phase transition of water in cartilage heated to about 70 degrees Celsius, some parts of cartilage matrix (proteoglycan units) became more mobile. The movement of these units takes place only when temperature exceed 70 degrees Celsius and results in alteration of tissue structure (denaturation). It is shown that (1) the maximal temperature is reached not on the surface irradiated at some distance from the surface; (2) surface temperature reaches a plateau quicker that the maximal temperature; (3) the depth of denatured area strongly depends on laser fluence and wavelength, exposure time and thickness of cartilage. The model allows to predict and control temperature and depth of structure alterations in the course of laser reshaping and treatment of cartilage.

When heated the living tissue exhibits temperature nonuniformities due to the vessel discreetness. On small scales the particular details of the vessel arraignments are practically unknown, so we regard such nonuniformities as random. When the tissue region affected directly by laser light is sufficiently small heat diffusion into the surrounding tissue is responsible for the necrosis growth. In this case strong temperature dependence of the thermal coagulation rate gives rise to the substantial perturbations the necrosis boundary due to the random temperature nonuniformities. In the previous papers we have analyzed this effect assuming the necrosis boundary quasiplane. In particular, we have found that for typical values of the tissue parameters the correlation length of such perturbations can be comparable with the necrosis size in magnitude. Therefore, the present paper studies the effect of the random temperature nonuniformities for a necrosis domain of spherical and cylindrical form. In this way we are able to analyze this effect for a more realistic situation, namely, depending on the form of an applicator delivering laser light inside the tissue. In particular, we have shown that for cylindrical applicators the effect of the vessel discreetness can be described by the developed previously model. For spherical applicators of small size (about several millimeters) this effect is depressed because in this case blood perfusion does not affect substantially the necrosis growth.

The Holmium laser has become established in orthopedic surgery and urology due to its unique combination of mechanical and thermal properties induced by explosive vapor bubbles. In a specialized setup, real-time high-speed and thermal images of dynamic vapor bubbles and thermal relaxation at a water tissue interface were obtained simultaneously. The thermal effects in the tissue model were correlated to the characteristics of the bubbles dependent on pulse energy (0.2 - 4 J), pulse repetition frequency (5 - 40 Hz), distance and angle of fiber delivery system (diameter 365 micrometer) to the tissue surface. Up to a fiber-to-tissue distance of 50% of the radius of the bubble, only a superficial tissue layer was heated. During bubble implosion, the tissue surface was attracted to the fiber, ripping of irregularities, and was effectively cooled by turbulence. In case of hard tissues, the bubble detached from the fiber imploding towards the hard surface. At closer distances (less than 50% of bubble radius), the tissue itself was vaporized resulting in mechanical damage and thermal relaxation into the tissue, especially above repetition rates of 5 Hz. There is a strong correlation between the path length of the free beam within the bubble and the degree of mechanical and thermal damage in the tissue directly irradiated by this beam. During clinical applications the surgeon should be aware of the size of the vapor bubble in relation to the distance and angle with the tissue for safe optimal use of the mechanical and thermal properties of the Holmium laser.

A 21 year old female was accidentally exposed in both eyes when she looked into the 10 cm exit aperture of a military laser designator emitting 1064 nm q-switched (30 ns) pulses at a 10 pulse per second rate. Steroid therapy (methylprednisolone sodium succinate) was initiated within 6 hours post exposure. Initial ophthalmoscopic observation revealed small contained macular hemorrhages in each eye. Fluorescein angiography (FA) showed minimal leakage. Visual acuity was 20/100 and 20/60 in OD and OS respectively. Contrast sensitivity in both eyes was depressed across all spatial frequencies by more than 1.5 log units. At four weeks post exposure, no significant macular scarring was apparent and visual acuity returned to 20/25 in both eyes. Contrast sensitivity had improved to normal levels with a peak at 3 cycles/degree. At one year post exposure, visual acuity was 20/13 in both eyes and measures of contrast sensitivity were within normal limits. During the course of recovery, the patient's fixation shifted from a slightly superior temporal site back to the central foveal region. The foveal lesion sites were still evident by ophthalmoscopy and Amsler grid measurements but were deemed functional when the patient placed small targets generated by the scanning laser ophthalmoscope in the lesion site for discrimination. This outcome indicates remarkable recovery of visual function and suggests that early administration of steroids may assist in preserving the natural neural recovery process of the photoreceptor matrix by minimizing intraretinal scar formation.

Laser induced stress waves are being used in a variety of medical applications, including drug delivery and targeted tissue disruption. Stress waves can also be an undesirable side effect in laser procedures such as ophthalmology and angioplasty. Thus, a study of the effects of stress waves on a cellular level is useful. Thermoplastic stress waves were produced using a Q-switched frequency-doubled Nd:YAG laser (lambda equals 532 nm) with a pulse duration of 4 ns. The laser radiation was delivered to an absorbing media. A thermoplastic stress wave was produced in the absorbing media and propagated into plated cells. The energy per pulse delivered to a sample and the spot size were varied. Stress waves were quantified. We assayed for cell viability and damage using two methods. The threshold laser parameters for cell damage were defined for three cell lines.

We present an interferometric technique to measure free surface velocities of a tissue phantom when subjected to a high power laser pulse. Such information is useful for the determination of the dynamic mechanical properties of tissues and tissue phantoms. We deliver a 4-nanosecond doubled Nd:YAG laser pulse to a tamped surface of a slab sample and probe the opposite free surface with a HeNe laser beam. The stress-wave induced motion of the rear-surface imparts a Doppler shift to the reflected HeNe probe. We monitor the Doppler shift with a velocity interferometer sensitive to velocities as low as 1 - 2 m/s.

A Q-switched frequency-doubled Nd-YAG laser coupled to an optical parametric oscillator generated 4.75 ns 800 nm laser pulses to create a subsurface acoustic wave in planar indocyanine green gel samples and flat segments of elastin biomaterial stained with indocyanine green. The acoustic waves traveled through the target and were detected by a piezoelectric transducer. The waveforms were converted to measurements of pressure (and temperature) as a function of depth in the material. An algorithm was developed and applied to the acoustic signals to extract information about the absorption coefficient as a function of depth in the samples.

Ultrashort pulsed laser retinal effects vary widely depending on the configuration of the laser energy as it reaches the retina and surrounding structures. Tissue response is determined by: wavelength, pulsewidth, energy per pulse, peak irradiance, linear optics of the beam path, and non linear optics of the ultrashort beam. In vivo, we have reported a range of lesions from visible and from near infrared ultrashort laser pulses. New data from additional infrared studies in vivo is combined with our previous data to present an overview of retinal effects and how these might be selected for retinal surgical use.

Single pulses in the near-infrared (1060 nanometers) were used to measure retinal spot size dependence of minimum visible lesion (MVL) thresholds in rhesus monkey eyes at a pulsewidth of 150 femtoseconds. We report the MVL thresholds determined at 1 hour and 24 hours post exposure which were obtained with 2 different lenses placed in front of the eye to vary the retinal spot size. Also we report the fluorescein angiography thresholds (FAVL) for the above measurements. These new data points will be added to the databank for Retinal Maximum Permissible Exposure (MPE) as a function of spot size for this pulsewidth and a comparison will be made with previous spot size dependency studies. Our measurements show that the retinal ED₅₀ threshold fluence decreases for increasing retinal spot sizes. The fluence at the MVL threshold decreased by a factor of 3 for an increase in retinal image diameter by a factor of 4.5 times from the smallest to largest spot size.

Laser threshold energies for artificial retinal damage from ultrashort (i.e. less than or equal to 1 ns) laser pulses are investigated as a function of both pulse width and spot size. A piece of film acts as the absorbing layer and is positioned at the focus of the Cain artificial eye (17 mm in water). We performed experiments at the focal point, and at two and ten Rayleigh ranges in front of the focus with the damage endpoint being the presence of a bubble coming off the film. Thresholds were determined for wavelengths of 1064 nm, 580 nm, and 532 nm with pulse durations ranging from the nanosecond (ns) to the femtosecond (fs) regimes. For the at-focus data in the visible regime, the threshold dropped from 0.25 (mu) J for a 5 ns pulse at 532 nm to 0.11 (mu) J for a 100 fs, 580 nm pulse. Similarly, for the near infrared (NIR) the threshold changed from 5.5 (mu) J for a 5 ns pulse to 0.9 (mu) J for a 130 fs pulse. These results are discussed in the context of applicable nonlinear optical phenomena.

Microscopic mechanisms of short pulse laser damage to melanin granules, the strongest absorbing chromophores of visible and near -- IR light in the retina and skin, are studied using the molecular dynamics simulations. The pulse width dependence of the fracture/cavitation and vaporization processes within the small particles, their coupling to the surrounding medium and the resulting tissue injury are discussed based on the simulation results. The effect of laser irradiation on an isolated submicron particle at different laser fluences and pulse durations is first analyzed. The mechanical disruption of the particle due to the laser induced pressure is found to define the character of damage for short pulse widths (tens of picoseconds) at laser fluences that ar significantly lower than those required for boiling. Thermal relaxation and explosive disintegration of the overheated particle at higher laser fluencies are the processes that dominate at longer laser pulses (hundreds of picoseconds). Damage of an absorbing particle embedded into a transparent medium with different mechanical characteristics is then simulated. Coupling of the acoustic and thermal pulses generated within absorbing particles to the surrounding medium is studied and the possible cumulative effects from an ensemble of absorbing particles are discussed. The simulation results provide the basis for future work in which the microscopic and continuum descriptions are combined for multiscale modeling of laser tissue interaction.

As part of a research program to understand and model eye damage produced by exposure to cw and pulsed lasers, the U.S. Air Force has created a granular model of laser retinal damage. The Thompson granular model simulates absorption of light by melanosomes distributed in the retinal pigmented epithelium, melanosome heating, and subsequent photothermal damage from bulk tissue heating. Various biological input parameters required for the model, such as the density, size, spatial distribution, and absorption coefficient of melanosomes, are not well known, creating uncertainty in the results. This problem is being addressed both experimentally, through measurements of biological parameters for various species, and theoretically, through analysis of parameter sensitivity in the model. In the current study, the parameter sensitivity was analyzed using a technique known as 'design of experiments,' which allows statistical estimation of the relative importance of independent experimental variables. A matrix of 20 cases has been analyzed, using 7 input parameters as independent variables. Cases have been confined to the long pulse regime (greater than or equal to 10 microseconds), where photothermal damage is dominant. Results were assessed using both temperature rise and Arrhenius damage integral values. Corneal fluence was found to be the most important physical parameter and melanosome absorption the most important biological parameter.

We have computationally modeled the generation of high pressures in melanosomes resulting from the absorption of sub- nanosecond laser pulses. The melanosome is treated as a solid sphere characterized by a bulk modulus, specific heat, coefficient of thermal expansion, and a uniform absorption coefficient. Using a series of partial differential equations to represent how the absorbed laser energy is converted to thermal and mechanical energy, we can calculate expected pressures resulting from laser pulses of any duration or fluence. We find that for the same fluence, the maximum pressure generated increases as the pulse duration decreases. For sub-nanosecond pulses, kilobar pressures can be generated inside the melanosome. We examine how the pressures that are generated depend on pulse characteristics and melanosome properties.

During optical breakdown, the energy delivered to the sample is either transmitted, reflected, scattered, or absorbed. The absorbed energy can be further divided into the energy required to evaporate the focal volume, the energy radiated by the luminescent plasma, and the energy contributing to the mechanical effects such as shock wave emission and cavitation. The partition of the pulse energy between these channels was investigated for 4 selected laser parameters (6 ns pulses of 1 and 10 mJ, 30 ps pulses of 50 (mu) J and 1 mJ, all at 1064 nm). The results indicated that the scattering and reflection by the plasma is small compared to plasma transmission. The plasma absorption can therefore be approximated by A approximately equals (1-T). The ratio of the shock wave energy and cavitation bubble energy was found to be approximately constant (between 1.5:1 and 2:1). For a more comprehensive study of the influence of pulse duration and focusing angle on the energy partition, we therefore restricted our measurements to the plasma transmission and the cavitation bubble energy. The bubble energy was used as an indicator for the total amount of mechanical energy produced. We found that the plasma absorption first decreases strongly with decreasing pulse duration, but increases again for pulses shorter than 3 ps. The conversion of the absorbed energy into mechanical energy is approximately equal to 90% with ns-pulses at large focusing angles. It decreases both with decreasing focusing angle and pulse duration (to less than or equal to 15% for fs-pulses). The disruptive character of plasma-mediated laser surgery is therefore reduced with ultrashort laser pulses.

We investigated the spatial distribution of energy dissipation during propagation of the shock front arising from optical breakdown in water, because it is related to the stress- induced cellular changes in plasma-mediated laser surgery. The dissipation can be calculated from the shock wave velocity (mu) _s by a relation derived from the Rankine-Hugoniot equation. (mu) _s was measured as a function of time and space for various laser parameters. With a 1 mJ/6-ns pulse, 64% of the absorbed light energy are converted into acoustic energy, but the largest part of this energy are converted into heat already within the first 200 micrometer of shock front propagation. Afterwards, the dissipation occurs at a much slower rate. Only approximately 10% of the acoustic energy reaches a distance of 10 mm. Far-field measurements can thus be very misleading for an energy balance. The energy dissipation at the shock front leads to a temperature rise of the medium. At 10 mJ pulse energy, the temperature close to the plasma exceeds the critical point of water. This means that the shock wave passage goes along with an enlargement of the cavitation bubble. High-pressure-induced bubble formation can also occur at locations further away from the laser plasma where shock waves from adjacent plasmas interfere. We have thus demonstrated a mechanism of stress wave induced cavitation which does not rely on tensiel stress, but on very high overpressures. Since most of the dissipation takes place within the first 200 micrometer, the shock wave effects are mostly covered by the effects of the cavitation bubble which reaches a radius of 800 micrometer in water at the same laser parameters. Acoustic tissue effects are, nevertheless important, because the bubble is smaller in tissue than in water, the weakening of the tissue structure by the shock wave passage probably contributes to the cavitation-induced damage, and the range for acoustic damage is larger in nonspherical geometries.

The development of thermal damage during pulsed Holmium:YAG ((lambda) equals 2.12 micrometer, (tau) _p equals 250 microseconds) irradiation of albumen was analyzed experimentally and numerically with the intent of validating the Arrhenius integral and investigating the influence of beam profile and dynamic changes in absorption. Fast flash videography was performed to document the transient development of coagulation during and after the laser pulse. A two-dimensional dynamic optical-thermal model was developed. The optical component involved a discretized Beer's law method in which absorption is a function of temperature. The thermal component was comprised of (1) a cylindrical coordinate (r,z) finite difference formulation of the heat conduction equation in which the output from the optical model was used as the source term and (2) a routine for calculating thermal damage using the Arrhenius relation. At the end of each time step, the temperature distribution was used to recalculate the absorption coefficient array, which in turn is used in the optical component. The model showed good agreement with experimental data and the literature. The Arrhenius integral was shown to be valid for the sub-vaporization pulsed laser regime. Experimental and numerical results indicated that spatial beam profile has a significant impact on thermal damage. Simulations predicted that at higher radiant exposures dynamic changes in absorption become more significant, accounting for a 10% increase in coagulation depth.

Temperature and shock wave propagation in water (as a model of tissue) irradiated by sub-picosecond and nanosecond pulses were modeled. The high temperature and pressure generated during sub-picosecond irradiation did not penetrate deeply into the water due to quickly ejected plasma while significant pressure and temperature increases were observed in deep regions with nanosecond pulses. Knowing that the sub- picosecond pulses are effective for tissue ablation, additional studies were done to examine the effect of short pulse widths (less than 20 ps). Ablation threshold, temperature rise and ablation crater quality on human dentine were investigated for different pulse widths in the range of 150 fs - 20 ps. The ablation threshold fluence was approximately 4 times higher with 20 ps pulses than with 150 fs pulses but the quality of the alation craters were not significantly different in this pulse width range.

Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. We describe here the development of new surrogate materials based on formulations incorporating chicken egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and human (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.

We investigated the acoustic signal of Er:YAG laser ablation in a gaseous environment. The high absorption coefficient of water at the laser wavelength of 2.94 micrometer leads to a small penetration depth of the Er:YAG laser pulses into tissue. The deposition of laser energy in a thin layer at the tissue surface causes a rapid evaporization of tissue water. The resulting tissue removal is used, for example, in laser skin resurfacing. The explosive evaporation of the tissue leads to an acoustic signal. We investigated the generation process of the signal caused by free-running laser pulses and its characteristic parameters in the time and frequency domain in correlation to the tissue and laser parameters with the aim to identify different tissues or tissue layers by analyzing the acoustic signal. Porcine skin and gelatin probes were ablated. Acoustic signals up to 1 MHz were measured using a condenser microphone and a piezoelectric airborne transducer. Schlieren photography was performed simultaneously to the acoustic investigations to visualize gaseous and condensed ablation products. We found that the high frequency content of the acoustic spectrum is due to shock waves created by each of the first laser spikes. Later in the laser pulse the acoustic signal is dominated by lower frequency components, because the generation of the high frequency components is inhibited by the interaction of the radiation with the ablation plume. The acoustic signature of free-running Er:YAG laser ablation seems to be particularly tissue specific during the first part of the laser pulse when the radiation interacts directly with the tissue.

A simulation code for analyzing laser matter interactions is described in the context of short pulse laser ablation of hard tissue. Some experimental results on short pulse laser absorption are presented and used to motivate employing such systems for ablating biological tissues. Results of simulations of hard tissue drilling are given, including hydrodynamic response and ablation efficiency.

This study was undertaken to investigate the feasibility of transmural capillary ingrowth into the inner surface of biosynthetic vascular prostheses (Omniflow^TM) through perforations created by an excimer-laser, thus inducing an endothelial cell coverage. The biosynthetic vascular prostheses (10 cm length, 6 mm (phi) ) were perforated with an excimer laser ((phi) of the holes 50 - 100 micrometer, distance 4 mm) and implanted into the carotid arteries of 8 sheep. The laser tissue interaction process of 193 nm radiation ensures minimal thermal damage to the prostheses. They were compared to untreated Omniflow^TM prostheses implanted at the contralateral side. Three months after implantation the prostheses were explanted and evaluated by gross morphology, histological examination and scanning electron microscopy. Scanning electron microscopy showed endothelial cells in the midgraft portion of all perforated prostheses, whereas collagen fibers, fibrin meshwork and activated platelets formed the inner layer in 6 out of 8 untreated Omniflow^TM prostheses. It can be concluded, that spontaneous endothelialization of biosynthetic vascular prostheses can be achieved by transmural capillary ingrowth through perforations in the wall of the prostheses in an experimental sheep model.

Laser radiation in the mid infrared region is a promising tool for soft tissue processing due to its strong absorption in water. In this study, a cw Tm:YAG laser emitting at 2.06 micrometer was used for basic investigations. The laser has a maximum output power of more than 30 W. Fresh pig skin, liver and heart tissue were irradiated at different intensities (up to 65 kW/cm²) and irradiation times (400 ms to 20 s). As a delivery system a 400 micrometer quartz fiber was used in contact as well as in non-contact mode. The irradiated samples were examined by light and electron microscopy. The ablation efficiency on soft tissue was determined to about 0.3 mg/J. The thermal induced damage covered a region of 100 to 500 micrometers lateral and 500 to 1000 micrometers axial to the crater. With regard to its compact dimensions and high efficiency the cw Tm:YAG laser appears to be a promising alternative to the CO₂ laser especially when fiber transmission of the radiation is required.

The generation of vapor-driven bubbles is common in many emerging laser-medical therapies involving soft tissues. To successfully apply such bubbles to processes such as tissue break-up and removal, it is critical to understand their physical characteristics. To complement previous experimental and computational studies, an analytic mathematical model for bubble creation and evolution is presented. In this model, the bubble is assumed to be spherically symmetric, and the laser pulse length is taken to be either very short or very long compared to the bubble expansion timescale. The model is based on the Rayleigh cavitation bubble model. In this description, the exterior medium is assumed to be an infinite incompressible fluid, while the bubble interior consists of a mixed liquid-gas medium which is initially heated by the laser. The heated interior provides the driving pressure which expands the bubble. The interior region is assumed to be adiabatic and is described by the standard water equation-of- state, available in either tabular, or analytic forms. Specifically, we use adiabats from the equation-of-state to describe the evolution of the interior pressure with bubble volume. Analytic scaling laws are presented for the maximum size and duration of bubbles as functions of the laser energy and initially heated volume.

We compare numerical simulations of bubble dynamics in water with experiments performed at the Medizineisches Laserzentrum Lubeck. Spatial and temporal features of the laser beam were modeled. Plasma growth was predicted using a moving breakdown model. We compare the measured and calculated positions of the shock front and the bubble wall as a function of time after optical breakdown in water. Nd:YAG laser pulses of 30-ps 1-mJ and 6-ns 10-mJ were simulated. We have extended previous work in which picosecond deposition was modeled at temporally instantaneous and spatially uniform.

A fluorescence-based temperature probe (optrode) was designed to measure temperature within laser-induced vapor bubbles. The optrode consisted of a 400-micrometer optical fiber with a rhodamine B-doped polyurethane film attached to the fiber tip. The film exhibited a fluorescence decay time of 4 ns, and the measured fluorescence yield was temperature dependent in the range from 20 to 110 degrees Celsius. A Ho:YAG laser ((lambda) equals 2.12 micrometer, (tau) _p equals 250 microseconds) with a pulse energy of 256 plus or minus 7 mJ delivered through a fiber was used to produce the vapor bubbles. The bubbles reached maximum expansion 200 microseconds after the onset of the laser pulse and had an average lifetime of 350 microseconds. The temperature was measured by positioning the optrode within the vapor bubble and exciting its fluorescent film-coated tip with a nitrogen dye laser ((lambda) equals 540 nm, (tau) _p equals 500 ps). At maximum expansion, the temperatures in the vapor bubbles were approximately 61 degrees Celsius, indicating sub-atmospheric saturated vapor pressures. The vapor pressure at maximum expansion was confirmed by Rayleigh's equation.

A frequency-doubled Nd:YAG laser at 532 nm with pulse durations of 2, 5, and 10 ms was used to ablate blood clot phantoms. The clot phantoms were prepared with 3.5% (175 Bloom) gel and Direct Red 81 dye to have an absorption coefficient of 150 cm^-1. Ablation thresholds were determined by a fluorescent technique using flash photography to detect the gel surface. The threshold was 15 plus or minus 2 mJ/mm² and corresponded to calculated temperatures of 80 plus or minus 10 degrees Celsius. Ablation efficiency experiments were conducted at 20 mJ. Ablation efficiencies were approximately 1.7 plus or minus 0.1 (mu) g/mJ for the millisecond pulses and were comparable to previously published efficiencies for ablation of clot with a 1 microsecond pulsed dye laser.

Laser optoacoustic imaging can be applied for characterization of layered and heterogeneous tissue structures in vivo. Accurate tissue characterization may provide: (1) means for medical diagnoses, and (2) pretreatment tissue properties important for therapeutic laser procedures. Axial resolution of the optoacoustic imaging is higher than that of optical imaging. However, the resolution may degrade due to either attenuation of high-frequency ultrasonic waves in tissue, or/and diffraction of low-frequency acoustic waves. The goal of this study was to determine the axial resolution as a function of acoustic attenuation and diffraction upon propagation of laser-induced pressure waves in water with absorbing layer, in breast phantoms, and in biological tissues. Acoustic pressure measurements were performed in absolute values using piezoelectric transducers. A layer or a small sphere of absorbing medium was placed within a medium with lower optical absorption. The distance between the acoustic transducer and the absorbing object was varied, so that the effects of acoustic attenuation and diffraction could be observed. The location of layers or spheres was measured from recorded optoacoustic pressure profiles and compared with real values measured with a micrometer. The experimental results were analyzed using theoretical models for spherical and planar acoustic waves. Our studies demonstrated that despite strong acoustic attenuation of high-frequency ultrasonic waves, the axial resolution of laser optoacoustic imaging may be as high as 20 micrometers for tissue layers located at a 5-mm depth. An axial resolution of 10 micrometers to 20 micrometers was demonstrated for an absorbing layer at a distance of 5 cm in water, when the resolution is affected only by diffraction. Acoustic transducers employed in optoacoustic imaging can have either high sensitivity or fast temporal response. Therefore, a high resolution may not be achieved with sensitive transducers utilized in breast imaging. For the laser optoacoustic imaging in breast phantoms, the axial resolution was better than 0.5 mm.

The feasibility of a noncontact all-optical probe for surface detection of laser-induced acoustic waves generated in buried absorbing objects was investigated. The goal is to detect subsurface optically absorbing objects, such as hemorrhages or vascularized tumors, which generate acoustic waves when slightly heated by a Q-switched laser pulse transported to an internal object by light diffusion within a turbid tissue. A dual-beam common-path interferometer was constructed to provide sensitive time-resolved detection of surface movements. Arrival of a pressure wave at one surface beam irradiation site before arrival at the other beam site caused a differential surface movement and a pathlength difference detected by the interferometer. The dynamic range of linear measurement was about 20 mbar - 200 bar at 20 mV/bar. The sensitivity (20 m V/bar) and noise level (10 - 30 mbar) of the interferometer matched or exceeded the performance of a lithium-niobate piezoelectric transducer. The point spread function of response was studied in liquid phantoms which demonstrated a null plane of no response in the plane symmetrically between the two beams. The ability to image an absorbing object at a depth of 11 mm within an aqueous phantom medium was demonstrated illustrating sub-mm resolution.

We compared infrared radiation measurement with stress wave measurement for real-time ablation monitoring during photorefractive keratectomy (PRK). We estimated temperature elevation which may be one of the most effective parameter for PRK monitoring, because the ablation mechanism is mainly attributed to thermal kinetics. The temperature elevation of ablated cornea was evaluated by the infrared radiation and the stress wave. The thermal radiation from irradiated cornea was detected by a MCT detector. The measured signal increased sharply just after the laser irradiation and decreased quasi- exponentially. We could calculate the temperature elevation by observed signal using Stefan-Boltzmann radiation law. In the case of the gelatin gel (15% wt) ablation in vitro, the temperature elevation was 97 deg. at 208 mJ/cm² in the laser fluence. We also measured transient stress wave by the acoustic transducer which was made by polyvinylidene fluoride (PVDF) film. The temperature elevation could be calculated from the peak stress amplitude based on the short pulsed laser ablation theory. The good agreement on the temperature elevation was obtained between the infrared and the stress based estimations. Due to non-contact and non-invasive method, our infrared measurements for temperature elevation monitoring may be available to accomplish the feedback control on the PRK.

Photoacoustic phenomenon has been investigated. An experimental protocol using photoacoustic principle has been proposed to image the regional distribution of electromagnetic energy absorption density in an object. This paper presents a rigorous method for photoacoustic image reconstruction. It is proved that photoacoustic image reconstruction is intrinsically a three-dimensional (3D) procedure. The spatial smear function (SSF) is introduced. An example using synthetic data proves the validity of photoacoustic image reconstruction theory proposed by the paper. The example shows that even the first order approximation of photoacoustic image reconstruction gives good agreement with the reality. It is also seen from the example that the accuracy and noise immunity of the reconstruction procedure depend on the experimental arrangement.

Oblique-incidence reflectometry was used to measure the optical properties of rat tumors with injected absorption- enhancement dye. The measured optical properties were used to model light delivery into the tissues for optimal therapeutic effects. The goal was to efficiently deliver the maximum amount of optical power into buried tumors being treated while avoiding potential damage to normal tissue caused by strong optical power deposition underneath the tissue surface illuminated by the laser beam. The distribution of power deposition was simulated for single beam delivery and multiple beam delivery as well. The simulated results showed that with an appropriate dye enhancement and an optimal laser delivery configuration, a high selectivity for laser treatment of tumors could be achieved.

A novel algorithm is demonstrated to determine the reduced scattering and absorption coefficients from time-resolved reflectance measurements at two positions on the surface of biotissue. The algorithm is very straightforward and fast, in which only some simple mathematical operations are involved, avoiding complicated iterative non-linear fitting to the time- resolved curve. The derived reduced scattering coefficient is not affected by whatever boundary condition is applied. The algorithm was verified using the time-resolved data from the Monte-Carlo model. Both the semi-infinite medium and the turbid slab medium were tested. In contrast to the non-linear fitting method, it is found using this algorithm that both the scattering and absorption coefficients can be determined to a high accuracy.

Sized-fiber array spectroscopy describes a device and method for measuring absorption and reduced scattering properties of tissue. The device consists of two or more optical fibers with different diameters (comparable to the optical path length in the tissue) that are used to measure the amount of light backscattered into each fiber. Each fiber is used for both irradiation and detection. Only one fiber emits and collects light at a given time. This paper presents Monte Carlo simulations of the sized-fiber device to indicate the behavior of a device with 50 and 1000 micrometer fiber sizes. Experimental results are presented for a device constructed with 400 and a 600 micrometer fibers that demonstrate the accuracy of the device in measuring the scattering coefficient of 10%-Intralipid samples over a reduced scattering coefficient range of 1 - 50 cm^-1.

For many skin treatments with light, it is important to have deep photon penetration into the skin. Because of absorption and scattering of photons by skin tissue, both the color and the diameter of the incident beam affect the penetration depth of photons. In this study, the dependence of light transmission through human skin tissues (ear lobs and between the fingers) has been measured in-vivo at six wavelengths (532 nm, 632 nm, 675 nm, 810 nm, 911 nm, and 1064 nm). The same measurement was also made on pig skin in-vitro for comparison. It was observed that (1) the photons at 1064 nm penetrate deeper than the other colors studied for a given incident beam diameter; and (2) the transmittance at a particular wavelength increases asymptotically with incident beam diameter. For some skin tissues, the transmittance flattens at about 8 mm for 532 nm photons and approaches saturation at about 12 mm for all other colors. The results on pig skin is similar.

The donated cornea transparency is one of the features to be analyzed previously to its indication for the transplant. Hence we have developed a system to evaluate the transmission spectrum of 'In Vitro' corneas in its preservative medium, in the range of 400 - 700 nm, to be implemented in an Eye Bank. The cornea in its preservative medium is illuminated by collimated white light beams which strike a diffraction grid, passes through an optical system and a selecting filter (400 - 800 nm) and then is detected by a linear CCD detector (2048 photodiodes). The data is displayed in a PC monitor via a commercial interface device. A dedicated software has been developed to plot the transmission spectrum profile and provide an objective and standard information about the transparency of the donated cornea.

The optical properties of seven native, seven laser-coagulated (Nd:YAG (lambda) equals 1064 nm, 11 W, 15 min, T less than or equal to 90 degrees Celsius), and seven thermally coagulated (60 min, T less than or equal to 80 degrees Celsius) samples of bovine myocardium were determined. The absorption coefficient (mu) _a, the scattering coefficient (mu) _s, and the anisotropy factor g were obtained in the spectral range from 1000 nm to 1500 nm from double integrating sphere measurements using an inverse Monte Carlo technique. The results indicate that both, laser coagulation and thermal coagulation increase the (mu) _a and (mu) _s values by a factor of 2 and 4, respectively, while g is not significantly changed. Conclusion: Thermal denaturation leads to significant changes in the optical properties of bovine myocardium. The changes are comparable to those induced by laser coagulation.

For pulsed laser tissue welding, an appropriate pressure needs to be applied to the tissues to achieve successful welds. In this study, we investigated the influences of pressure on in vitro optical properties of elastin biomaterial. The optical properties were measured as a function of pressure with a double integrating-sphere system. A He-Ne laser (633 nm) was used for all measurements. Each sample was sandwiched between microscope slides and then compressed with a spring-loaded apparatus. Transmittance and diffuse reflectance of each sample were measured under a pressure (0 - 1.5 kg/cm² and then released to 0). Absorption and reduced scattering coefficients were calculated using the inverse doubling method from the measured transmittance and reflectance values. Results from this study demonstrated: (1) The overall transmittance increased while the reflectance decreased as the tissue thicknesses were reduced up to 72% and the tissue weights were decreased about 40%, (2) The absorption and scattering coefficients increased with increasing the pressure, and (3) The pressure effects on the tissue optical properties were irreversible. Possible mechanisms responsible for the changes in the tissue optical properties were also investigated by changing tissue thicknesses or weights (through dehydration). This study implies that changes in tissue thickness and water content are important factors that affect tissue optical properties in different ways.

Pulse-to-pulse kinetics of laser ablation of porcine cornea in vitro by a YAG:Er laser ((lambda) equals 2.94 micrometer) and by fifth harmonic of a YAP:Nd laser ((lambda) equals 216 nm) as well as preablation transformations of cataracted human lens in vitro irradiated by Glass:Er laser ((lambda) equals 1.54 micrometer) are followed by Optical Coherence Tomography (OCT). In the latter case kinetics of tissue swelling is studied. Observation of tissue surface with temporal resolution better than pulse train duration by means of cw probe laser reveals evidences of outburst of 'dynamic' hump.

Optical parameters (scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g) of hyaline cartilage were studied for the first time. Optical properties of human and pig nasal septum cartilage, and of bovine ear cartilage were examined using a spectrophotometer with an integrating sphere, and an Optical Multi-Channel Analyser. We measured total transmission T_t, total reflection R_t, and on-axis transmission T_a for light propagating through cartilage sample, over the visible spectral range (14000 - 28000 cm^-1). It is shown that transmission and reflection spectra of human, pig and bovine cartilage are rather similar. It allows us to conclude that the pig cartilage can be used for in-vivo studies instead of human cartilage. The data obtained were treated by means of the one-dimensional diffusion approximation solution of the optical transport equation. We have found scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g by the iterative comparison of measured and calculated T_t, R_t and T_a values for human and pig cartilage. We found, in particular, that for 500 nm irradiation s equals 37,6 plus or minus 3.5 cm^-1, g equals 0,56 plus or minus 0.05, k approximately equals 0,5 plus or minus 0.3 cm^-1. The above data were used in Monte Carlo simulation for spatial intensity profile of light scattered by a cartilage sample. The computed profile was very similar to the profile measured using an Optical Multi-Channel Analyzer (OMA).

The efficiency of light absorption by oxyhemoglobin and deoxyhemoglobin in cutaneous blood vessels in dependence of the radiation wavelength and optical properties of the tissue is investigated. The main goal is to develop the practical application of long pulse flashlamp-pumped dye lasers in the treatment of different cutaneous lesions, based on the selective photothermolysis. The spectra of laser action both on oxyhemoglobin and deoxyhemoglobin of blood vessels at different depths of the tissue layer were calculated using the Kubelka-Munk optical model of the tissue. The obtained results allow to choose the proper wavelength of laser radiation for the selective and efficient influence on the blood chromophores. It is shown that for blood vessels located in tissue up to the depth of 2500 (mu) the action spectra of laser radiation follow the shape of the Q - absorption bands of oxyhemoglobin and deoxyhemoglobin. At deeper layers the action spectra become very narrow ((delta) (lambda) on the order of magnitude 25 - 30 nm) and shift to the long wavelength with maximum at 585 nm and 570 nm for oxyhemoglobin and deoxyhemoglobin, accordingly. The action spectra in the near infrared region remain very broad and cover the range from 600 nm to 1200 nm. It is shown that these bands play the dominant role in the absorption of laser radiation in deeper layers of tissue.

The purpose of a simulated operation system in craniofacial surgery is to evaluate and visualize the results of operations on the overall facial shape of the patient and on the functionality of his jaw. This paper presents the analyzation of muscle movements in the mastication system by applying real jaw movements to the simulation. With this method an accurate modeling of the mastication muscles can be performed which is a prerequisite for a realistic simulation and precise intra- operative registration. According to this results a large- scale musculoskeletal model of the mastication system is generated including kinematic and dynamic parameters. By integrating distance sensors in the simulation of a segmented CT (computer tomograph) image of the maxilla and mandible the motions of the masticatory muscles during different kinds of jaw movements have been analyzed. The data for this motions have been recorded by a commercial system (CONDYLOCOMP LR3) on a test person and transformed to the graphical simulation system. This method for the first time allows to observe the dynamics of the mastication muscles and their different parameters like muscle length ratio and velocity. The integration of a kinematic model for the jaw movement makes it possible to analyze non traced movements.

We introduce a mathematical primitive called the B-spline solid that can be used to create deformable models of muscle shape. B-spline solids can be used to model skeletal muscle for the purpose of building a data library of reusable, deformable muscles that are reconstructed from actual muscle data. Algorithms are provided for minimizing shape distortions that may be caused when fitting discrete sampled data to a continuous B-spline solid model. Visible Human image data provides a good indication of the perimeter of a muscle, but is not suitable for providing internal muscle fiber bundle arrangements which are important for physical simulation of muscle function. To obtain these fiber bundle orientations, we obtain 3-D muscle fiber bundle coordinates by triangulating optical images taken from three different camera views of serially dissected human soleus specimens. B-spline solids are represented as mathematical three-dimensional vector functions which can parameterize an enclosed volume as well as its boundary surface. They are based on B-spline basis functions, allowing local deformations via adjustable control points and smooth continuity of shape. After the B-spline solid muscle model is fitted with its external surface and internal volume arrangements, we can subsequently deform its shape to allow simulation of animated muscle tissue.

Rigid Body Modeling, a 6 degree of freedom (DOF) method, provides state of the art human movement analysis, but with one critical limitation; it assumes segment rigidity. A non- rigid 12 DOF method, Pliant Surface Modeling (PSM) was developed to model the simultaneous pliant characteristics (scaling and shearing) of the human body's soft tissues. For validation, bone pins were surgically inserted into the tibia and femur of three volunteers. Infrared markers (44) were placed upon the thigh, leg, and bone pin surfaces. Two synchronized OPTOTRAK/3020^TM cameras (Northern Digital Inc., Waterloo, ON) were used to record 120 seconds of treadmill gait per subject. In comparison to the 'gold standard' bone pin rotational results, PSM located the tibia, femur and tibiofemoral joint with root mean square (RMS) errors of 2.4 degrees, 4.0 degrees and 4.6 degrees, respectively. These performances met or exceeded (P less than .01) the current state of the art for surface data, Rigid Surface Modeling. The thigh's measured surface experienced uniform repeatable changes in scale: 40% mediolateral, 5% anterioposterior, 5% superioinferior, and planar shears of: 25 degrees transverse, 15 degrees sagittal, 5 degrees frontal. With the brief exception of push-off, the lower leg demonstrated much greater rigidity: less than 5% scaling and less than 5 degrees shearing. Thus, PSM offers superior 'rigid' estimates of knee motion with the ability to quantify 'pliant' surface changes.

The product of the ob-gene named leptin is correlated with body fat mass in humans. Little evidence exists if the same holds true for body fat distribution. In this study we therefore investigated plasma leptin levels and the subcutaneous adipose tissue topography (SAT-Top) by means of the newly developed optical device Lipometer before and after a 3 week weight reduction camp. Thirty four obese boys (mean age 12a) took part in this study. Body fat distribution were assessed by means of Lipometer to measure the thickness of a subcutaneous fat layer at 15 standardized body sites (SAT- Top). Plasma leptin levels (LL) were measured by radioimmunoassay. All measurements were taken at the beginning and at the end of the camp. By dividing all boys according chronological age (group A: age less than 12a, n equals 17/group B: greater than 12a, n equals 17) we found correlations with the combination of measured body sites (MBS) before (A: MBS vs. LL, R² equals 0.79; p less than 0.01/B: MBS vs. LL, R² equals 0.35; n.s.) and after (A: MBS vs. LL, R² equals 0.83; p less than 0.01/B: MBS vs. LL, R² equals 0.70; p less than 0.01) the intervention. Our study confirms that the subcutaneous adipose tissue topography (SAT- Top) by means of the optical device Lipometer serves as a marker of plasma leptin levels in obese boys and highlights the use of this optical device in a predictive manner.

Recent advances in obesity research have shown that the product of the ob-gene named leptin is related to total body fast mass in humans. There is, however, a debate if leptin levels are pulsatile and linked to body fat distribution. In this study we therefore investigated the subcutaneous adipose tissue topography (SAT-Top) measured by means of the newly developed device Lipometer and leptin levels during a 24 hours beginning at 0715am ending the same time in the next day. Blood samples for measurement of leptin were taken every 3 hours in a male subject. Measurements of SAT-Top were performed at 15 body sites from neck to calf at the left and right body site at the same time interval. We observed an almost symmetrically reaction of the left and right body site with a maximum of the mean value of all body sites in the evening at 0715pm. There was a negative correlation between serum leptin levels and SAT-Top using the set of certain body sites (R² equals 0.80, p equals 0.01). If these combination of body sites is inversed and set against serum leptin levels, both curves show almost identical shape and time dependence. We conclude that SAT-Top by means of Lipometer is changed in a short time and related to leptin levels in the investigated male subject.

Comparative studies of oxygen consumption, surface activity, photodestruction of erythrocytes and hemoglobin were carried out during photodynamic reaction in human blood with Phthalocyanines, Chlorines, Porphyrins and Methylene blue photosensitizers in vitro.

Image segmentation and anatomical registration play an important role in subject-specific computational modeling and image analysis. Often a three-dimensional (3D) segmentation is available for a canonical template image dataset of a single subject. The goal of the present work is to apply this a priori knowledge to facilitate segmentation of anatomical structures in other subjects. A 'Warping' method was developed to deform the template anatomy and register it with specific target anatomies. This was achieved by direct incorporation of image data into a nonlinear finite element (FE) analysis program. The algorithm searches all admissible material configurations for the one which minimizes the difference between the target and the deformed template. FE models of specific anatomical structures were generated from the anatomy of one specific template subject. The FE model deforms under the laws of nonlinear continuum mechanics such that one-to-one correspondence of differential lines, areas, and volumes is guaranteed. The method has been successfully applied to 2D and 3D segmentation, registration, and geometrical model construction. Example results are provided for segmentation of the distal femur using X-ray computed tomography (CT) data, and registration of neuroanatomical structures using optical cryosection image data.

A new method has been developed to extract tissue strain from a sequence of two or more medical images. This was achieved by deforming a finite element (FE) model of the tissue under loads derived from the spatial differences between two sets of image data. One image data set deforms with the tissue, while the other remains stationary. The final configuration aligns the two sets of image data. The method accounts for convection of material points, modification of the Lagrangian material properties, and probabilistic features of the sensor. A FE model of the tissue must be constructed and assigned material properties. Image data are assigned to the model tissue such that the reference configuration of the FE model corresponds to one image. The image data is subject to change during the deformation. A nonlinear solution method determines the material configuration that minimizes the difference between the deformed image (deformed template) and the experimentally observed image (target image). In many cases the image data provide powerful constraints which allow estimation of material deformation even in the absence of known loads and/or boundary conditions. The method has been applied to estimate the motion and distribution of strain using MR and CT data.

The purpose of this study is to determine the soft tissue thickness around the face using A-scan ultrasound, for incorporation into a 3D head model as a design tool for safety equipment and facial prostheses for patients following maxillofacial reconstruction. Using very high frequency A-scan ultrasound allows the superficial tissue to be measured on volunteers without risk. The investigation covers 112 points on half of the face, linked to 11 defined morphological zones. The zonal boundaries are based on previous research and are initially identified by palpation of the face. The thickness of the facial soft tissue varies greatly between individuals but the calculations of average and standard deviation coefficients reveal that the distribution of the features in the same zone of an individual fits within a normal range of variation. The measurements presented for the thickness of soft tissues at different parts of the face can also be recommended for specialists in craniofacial identification. The results of this study will be presented and indications of its application to FEA modeling outlined.

The purpose of this study is to incorporate thickness data into a soft tissue model in a laser scanned head data base, for use in FEA modeling of the behavior of the soft tissue layer under mechanical loads. Using a magnetic-based, spatial acquisition system (Polhemus) into which is incorporated an ultrasound sensor the position and orientation of tissue thickness vectors are obtained. By combining this with 3D high resolution head shape data from our laser scanner, a model of the head complete with soft tissue thickness is to be developed. We have implemented an initial version of software for the integration of laser scanning and facial soft tissue thickness measurement. The package displays facial images and performs basic imaging processing. The co-ordinate systems of the two methods are matched with the help of markers fixed on known head landmarks and a 3D digitiser (Polhemus). The computed source locations can be instantly superimposed on the facial images during the analysis.

For more than a decade, surgical procedures have benefited significantly from the advent of OR (operating room) coregistered preoperative CT (computed tomographic) and MR (magnetic resonance) imaging. Despite advances in imaging and image registration, one of the most challenging problems is accounting for intraoperative tissue motion resulting from surgical loading conditions. Due to the considerable expense and cumbersome nature of intraoperative MR/CT scanners and the lack of high spatial definition of intracranial anatomy with ultrasound, we have elected to pursue a physics-based computational approach to account for tissue deformation in the context of frameless steroetactic neurosurgery. We have developed a computational model of the brain based on porous media physics and have begun to quantify subsurface deformation due to comparable surgical loads using an in vivo porcine model. Templates of CT-observable markers are implanted in a grid-like fashion in the pig brian to quantify tissue motion. Preliminary results based on the simplest of model assumptions are encouraging and have predicted displacement within 15% of measured values. In this paper, a series of computations is compared to experimental data to further understand the impact of material properties and pressure gradients within a homogeneous model of brain deformation. The results show that the best fits are obtained with Young's moduli and Poisson's ratio which are smaller than those values typically reported in the literature. As the Poisson ratio decreases towards 0.4 the corresponding Young's modulus increases towards the low end of the values contained in the literature. The optimal pressure gradient is found to be within physiological limits but generally higher than literature values would suggest for a given level of imparted loading, although differences between our experiments and those in the literature with respect to tissue loading conditions are noted.

A photomechanical damage mechanism in abosrbing regions or particles surrounded by a non-abosrbing medium after irradiation with a short laser pulse is investigated experimentally and theoretically. In tissue, such absorbers are for example melanosomes, blood vessels or tatoo pigments. It follows from theoretical considerations that the photoacoustic wave caused by irradiation of a spatially limited volume contains both compressive and tensile stress. Experiments were performed to test whether these tensile stresses cause cavitation in absorbers of spherical or cylindrical shape. High-speed video images of liquid spheres or gelatin cylinders (diameters 200 to 300 micrometer) suspended in oil showed that cavitation occurs at the center of the spheres or on the cylinder axis, respectively, shortly after irradiation with a light pulse (6 ns duration) from an optical parametric oscillator. The cavitation effect was observed at maximum temperatures below and above the boiling point and at ratios of the absorber size on the absorption length larger and smaller than one. The experimental findings are supported by theoretical calculations, from which strong tensile stresses are predicted in the interior of the absorbers, even if the values of acoustic impedance inside and outside the absorbing volume are equal. The reported effect is believed to cause damage to absorbers if the pulse duration is short enough to provide stress confinement, that is if the time an acoustic wave needs to cross the abosrbing region is longer than the pulse duration. For small absorbers such as melanosomes with a size of about 1 micrometer this requires a laser pulse duration in the picosecond regime.

A method is presented to simulate the light propagation in turbid media. Based on a numerical algorithm to solve the time-dependent diffusion equation, the method takes into account spatial variations of the reduced scattering and absorption factors of the medium due to the presence of objects as well as random fluctuations of these factors. The simulation results for tissuelike phantoms are compared to experimental data and excellent agreement is found. The technique is employed to explore the possibility of locating millimeter-sized objects, immersed in turbid media, from time- resolved measurements of the transmitted or reflected (near- infrared) light. A method is proposed to enhance the imaging power of the time-resolved technique. Using the data- processing technique we find that it is possible to detect 1 mm-diameter objects, independent of their location within the sample and under unfavorable conditions. Experimental data of a time-resolved reflection experiment on a 1 mm diameter tube filled with blood and embedded in an intralipid solution are presented. The results show that, using the data processing technique, it is possible to detect the tube to a depth of 15 mm from the illuminated surface in a 70 mm thick sample. Simulation data are in excellent agreement with these experimental results.