Steven L. Jacques

Three Monte Carlo programs of polarized light transport into scattering media: part II.

Propagation of light into scattering media is a complex problem that can be modeled using statistical methods such as Monte Carlo. Few Monte Carlo programs have so far included the information regarding the status of polarization of light before and after a scattering event. Different approaches have been followed and limited numerical values have been made available to the general public. In this paper, three different ways to build a Monte Carlo program for light propagation with polarization are given. Different groups have used the first two methods; the third method is original. Comparison in between Monte Carlo runs and Adding Doubling program yielded less than 1 % error.

Pressure effects on soft tissues monitored by changes in tissue optical properties

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.

Design and testing of an endoscopic photoacoustic probe for determination of treatment depth after photodynamic therapy

An endoscopic photoacoustic probe is designed and tested for use in PDT treatment of esophageal cancer. The probe, measuring less than 2.5 mm in diameter, was designed to fit within the lumen of an endoscope that will be inserted into an esophagus after PDT. PDT treatment results in a blanched, necrotic layer of cancerous tissue over a healthy, deeper layer of perfused tissue. The photoacoustic probe was designed to use acoustic propagation time to determine the thickness of the blanched surface of the esophagus, which corresponds to treatment depth. A side-firing 600 micrometers fiber delivered 532 nm laser light to induce acoustic waves in the perfused layer of the esophagus beneath the blanched (treated) layer. A PVDF transducer detected the induced acoustic waves and transmitted the signal to an oscilloscope. The probe was tested on clear and turbid tissue phantom layers over an optically absorbing dye solution.

Laser welding of biomaterials stained with indocyanine green to tissues

This paper considers some issues pertinent to laser welding of elastin-based biomaterials to tissues using a pulsed diode laser (lO-is pulse) and indocyanine green (ICG) as an absorbing chromophore to localize laser heating to the weld surface, the elastin/tissue interface where welding occurs. Experiments involved laser welding of elastin heterographs to the intimal surface of the carotid artery (in vitro, porcine) as a -4x5 spotweld, then determining the breaking strength when the two tissues were pulled in a direction parallel to the plane of the spot weld while submerged in water. The questions answered are: . WHAT IS THE PEAK TEMPERATURE REQUIRED FOR WELDING ELASTIN HETEROGRAPH TO THE INTIMAL SURFACE OF CAROTID ARTERY? ANSWER: 3OO °C threshold, -6OO °C for maximum strength. This estimate is based on optical measurements of dye accumulation in stain layer and measurements of thickness of stain layer via fluorescence microscope examination. . WHATIS THE DEPENDENCE OF WELD STRENGTH ON THE LASER EXPOSURE? ANSWER: Breaking force (g) = Max*(1 exp(-(E Eth)/U67)), where Max is the maximum strength achievable by laser welding, expressed as the breaking force in g when elastin heterograph and tissue are pulled. E is the laser pulse energy. Eth is the apparent threshold laser pulse energy that will break the weld. Uth is the laser energy above threshold which achieves 67% of Max. Max was about 15 g for the -2O --2weld area of our experiments. Eth was 0.8 J. U67 was 1 .44 J. . DOES WELD STRENGTH DEPEND ON HYDRATION CONDITIONS? ANSWER: Not on the amount of excess unbound water. There was no significant difference in weld strength between welding dripping wet tissues vs well blotted tissues. S WHAT DIFFERENCE IS THERE BETWEEN IRRADIATING THE WELD SURFACE THROUGH THE BIOMATERIAL VS THROUGH THE TISSUE, WHEN THE BIOMATERIAL IS PARTIALLY STAINED WITH ICG? ANSWER: There is a difference if the stain layer is heavily stained. Irradiation through the tissue allows direct irradiation on the weld surface which achieves the highest peak temperatures for the least laser pulse energy. Irradiation through the elastin heterograph causes direct irradiation of the rear surface of the stain layer, within the biomaterial and away from the weld surface, and thermal diffusion must bring the heat to the weld surface. This difference occurs only when the absorption by the stain layer is sufficiently high that little laser energy directly reaches the weld surface.

Iterative reconstruction method for three-dimensional optoacoustic imaging

Three-dimensional optoacoustic imaging uses detection of laser-generated thermoelastic waves with an ultrasound sensor array. Integrated acoustic signals (velocity potentials) are back projected into the source volume to give a map of absorbed laser energy. Since the number of array elements and the receiving solid angle are limited, radial back projection produces artifacts such as back projection arcs. To solve this problem, we developed in this study an iterative method for image reconstruction. A first image estimate was generated by simple radial back projection. A model for signal generation from a volume containing arbitrary optoacoustic sources was then used to calculate acoustic wave propagation from this estimate. Calculated signals at the array elements were compared with the measured signals and the difference was used to improve the image. In simulations and experiments we used the algorithm to obtain three-dimensional images of multiple optoacoustic sources. With signals from an array of 3 x 3 detector elements a significant improvement was observed after about 10 iterations compared to the simple radial back projection. Although computationally more intensive, iterative reconstruction can minimize the time and instrumentation for signal acquisition because a small number of array elements already gives a good quality optoacoustic image.

Polarized light imaging of tissues

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Sized-fiber array spectroscopy

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.

Evaluating outcomes of palliative photodynamic therapy: instrument development and preliminary results

Background: Subjective measures are considered the gold standard in palliative care evaluation, but no studies have evaluated palliative photodynamic therapy (PDT) subjectively. If PDT is to be accepted as a palliative therapy for later-stage obstructing esophageal and lung cancer, evidence of its effectiveness and acceptability to patients must be made known. Study Design/Materials and Methods: This ongoing studys major aim is to evaluate subjective outcomes of PDT in patients with obstructing esophageal and lung cancer. Existing measures of health status, dysphagia and performance status were supplemented with an instrument developed to evaluate PDT symptom relief and side effect burden, the PDT Side Effects Survey (PSES). Results: PDT patients treated with porfimer sodium (Photofrin) and 630-nm light experienced reduced dysphagia grade and stable performance status for at least one month after PDT (N= 10-17), but these effects did not necessarily persist at three months. Fatigue, appetite and quality of life may be the most burdensome issues for these patients. Conclusions: Preliminary data suggest that the PSES is an acceptable and valid tool for measuring subjective outcomes of palliative PDT. This study is the first attempt to systematically evaluate subjective outcomes of palliative PDT. Multi-center outcomes research is needed to draw generalizable conclusions that will establish PDTs effectiveness in actual clinical practice and enhance the wider adoption of PDT as a cancer symptom relief modality.

Evaluating clinical outcomes of PDT

Efficacy studies are required for regulatory approval of new medical treatments in the United States and elsewhere. Although efficacy studies may demonstrate safety and efficacy, they are not always sufficient for characterizing the effects of a treatment in actual clinical practice. Ongoing outcomes research is necessary to identify outcomes of treatment and treatment patterns in actual clinical practice. Criteria for evaluating palliative treatments in outcomes research must reflect the treatments capacity to relieve symptoms while entailing minimal risks and adverse effects. However, the measurement of symptom relief as a result of treatment is prone to error because symptoms are inherently subjective and may be influenced by a variety ofnon-treatment factors, such as individual perception, physical exertion, and concurrent symptom management strategies. PDT patients treated with Photofrin® and 630-nm light at our center have had reduced dysphagia grade and stable performance status for approximately one month after PDT (N= 7-26), but these effects did not necessarily persist at the three-month followup interval. Preliminary data on five patients collected in a pilot study of a new symptom burden measurement tool suggest that the perceived burden ofphotosensitivity may increase with time. Fatigue, poor appetite and decreased overall quality of life appear to be the most troubling symptoms for our late-stage esophageal cancer PDT patients. The least burdensome symptoms were anxiety, pain and depression.

Modeling pressure waves generated by pulsed laser irradiation of irregularly shaped absorbing objects within media

Optoacoustic imaging is an imaging technique based on the time-resolved arrival of sound waves at an array of pressure transducers on the tissue surface, where the sound waves were generated by thermoelastic expansion of optically absorbing objects within the tissue when heated by a pulsed laser. This paper discusses the time-resolved pressures and velocity potentials create by pulsed laser irradiation of absorbing objects of varying shape, as well as the process of back-projection of such data to create an optoacoustic image of the distribution of absorbing objects.