This PDF file contains the front matter associated with SPIE Proceedings Volume 7175, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.

This paper deals with the optical properties of human tissues that are measured using laser reflectometry method. The result is compared with the phantom and simulation values to get accurate result. The surface Backscattering was determined by laser reflectometry. The tissue equivalent phantom would be prepared with the help of white paraffin wax mixed with various colour pigments in multiple proportions. A familiar Monte Carlo Simulation is used for the analysis of the optical properties of the tissue. The normalized backscattered intensity(NBI) signals from the tissue surface, measured by the output probes after digitization are used to reconstruct the reflectance images of tissues in various layers below the skin surface. From NBI profiles measured at various locations of the tissues on the forearm the corresponding optical parameters, the scattering (ms ) and absorption(ma) coefficient and the anisotropy parameter (g) ,by matching these with profiles as simulated by Monte Carlo procedure are determined.

The changes of Raman spectra from ex-vivo porcine aorta tissues were studied before and after laser tissue welding (LTW). Raman spectra were measured and compared for normal and welded tissues in both tunica adventitial and intimal sides. The vibrational modes at the peak of 1301 cm^-1 and the weak shoulder peak of 1264 cm^-1 of amide III for the normal tissue changed to a peak at 1322cm^-1 and a relative intense peak at 1264cm^-1, respectively, for the welded tissue. The Raman spectra were analyzed using a linear regression fitting method and compared with characteristic Raman spectra from proteins and lipids compounds. The relative biochemical molecular composition changes of proteins (Collagen types I, III, V and Elastin) and lipids for the laser welded tissue were modeled by basis biochemical component analyses (BBCA) and compared with the normal tissue.

This paper presents a study for in-vivo estimation of optical properties of pigmented skin tumor by oblique incidence diffuse reflectance spectroscopy. The developed system has been tested in clinical conditions to compare the optical properties of melanomas, dysplastic nevi and common nevi. The spatio-spectral data are collected in the wavelength range of 455 to 765 nm from 96 pigmented skin lesions including 10 histopathologically diagnosed as melanoma, 67 as dysplastic nevi and 19 lesions as common nevi. The preliminary results indicate significantly larger average reduced scattering coefficient spectra for malignant and dysplastic lesions than for benign common nevi.

The terahertz (THz) region of the electromagnetic (EM) spectrum is defined as frequencies ranging from 0.1 to 10 THz. The optical properties of biological tissues have been characterized in neighboring spectral regions; however, few studies have been conducted that have examined these properties in the THz wavelength range. In this study, we used a far-infrared optically-pumped terahertz laser system, a reflection spectrometer system, and photothermal radiometric techniques to characterize the optical properties of water and biological tissues. The reflection spectrometer system performed well at lower frequencies, but proved to be unsuitable for frequencies greater than 2.52 THz. The suboptimal performance was determined to be primarily due to the higher transmission losses of the lenses, and the increased atmospheric losses that are associated with higher terahertz frequencies. The waveguide studies corroborated these findings and served to demonstrate that purging the laser beam path with nitrogen gas was an effective way to markedly reduce THz beam propagation losses. Given this finding, we have designed a temperature-controlled, nitrogen gas purged THz enclosure. The preliminary studies using photothermal radiometric techniques appeared to provide reasonable measures for the absorption coefficient (μa) of water at THz frequencies. In future studies, the tissue property measurements will made within the custom-designed enclosure using photothermal radiometric techniques.

We experimentally characterized the angular distribution and proportion of minimally deviated quasi-ballistic photons versus multiply scattered photons in a turbid medium. The study examined the angular distribution of photons propagating through and exiting the highly scattering medium over a narrow range about the axis of a collimated light source in trans-illumination mode. The measurements were made using an angular domain imaging system that employed one of three silicon micro-machined arrays of micro-tunnels each with a different range of acceptance angles. The balance between quasi-ballistic photons and unwanted multiply scattered photons accepted by the micro-machined angular filters was measured in order to determine the optimum range of acceptance angles for the system. The experiments were performed in tissue mimicking phantoms using a 1-cm thick optical cell with 0.7% Intralipid^TM and an 808 nm diode laser. A maximum spatial resolution and contrast of 150 μm and 6% were observed by selecting the proper acceptance angle, respectively. Image contrast was improved further (about 10 times) by subtraction of the background signal representative of the multiply scattered photons by inserting an optical wedge into the light path. The measurements indicated that the highest spatial resolution and contrast for trans-illumination images through the sample were obtained for the angular filter with an angular acceptance range of 0.4° to 0.5°. It was concluded that this range of acceptance angles was small enough to attenuate the majority of multiply scattered photons, but still accept a significant proportion of quasi-ballistic photons, thereby optimizing both image resolution and contrast.

Angular Domain Imaging is an optical tomography technique that filters out scattered light by accepting only photons with small deviation angles from their original trajectories. Previously, angular filters of linear collimating array (0.29° acceptance) or spatiofrequency filter of a +50mm lens with a 214um aperture (0.25° acceptance) were used. In the linear collimating array system, using a wedge prism to deviate the light source by 2-3x the acceptance angle creates a second image of only the scattered components which can then be subtracted from the filtered image to enhance detectability. We now apply this technique to the spatiofrequency filter system at an angle 2x the acceptance. Utilizing several wavelengths of laser sources with different beam symmetries, test phantoms are placed in a 5cm thick sample of diluted intralipid solution, with a maximum SR of 1.64×10⁶:1 (μs' = 1.8cm^-1). By digitally subtracting the background scattered light, test phantoms previously unobservable are now distinguishable. Using background subtraction, the SR limitation of the SFF system improves 3x under full illumination and ~40x under line of light illumination. The improvement under partial illumination is similar to the result using the collimator array, but with resolution limited by the optics used in the system.

We report results of a study to evaluate effectiveness of a mechanical tissue optical clearing device (TOCD) using optical coherence tomography (OCT). The TOCD consists of a pin array and vacuum pressure source applied directly to the skin surface. OCT images (850 and 1310 nm) of in vivo human skin indicate an increased light penetration depth (enhanced approximately 2 fold over peripheral tissue) which spatially correlates with TOCD pin indentations. Increased contrast of the epidermal-dermal junction in OCT images spatially correlates with indented zones. OCT M-scans (time sequence of depth scans) indicate optical penetration depth monotonically increased throughout the entire image acquisition period with most improvement at early times of TOCD application with vacuum. Results of our study suggest that mechanical optical clearing of skin may provide a means to deliver increased light fluence to dermal and subdermal regions.

The primary and the secondary goals of this study were to investigate the change in morphology and optical properties of sclera due to a hyperosmotic agent i.e. 100% anhydrous glycerol. We performed our experiments in vivo on the sclera of 8 rabbits and 3 miniature pigs. All the animals were under anesthetic for the entire experiment according to an approved protocol. The position of the eye was stabilized with a suture placed in the limbus. Glycerol was delivered to sclera in 2 methods (i) injection (using a hypodermic needle 27G ½), (ii) direct application after 0.3 cm incision at conjunctiva. A camera attached to a slit lamp was used to capture the morphological changes of the sclera. For the secondary goal we used a diffuse optical spectroscopy (DOS) system with a linear fiber arrangement to measure reflectance from the sclera before and after application of glycerol. The probe source-detector separation was set to 370 μm for optimal penetration depth. We fit the measured diffuse reflectance to a Lookup Table (LUT)-based inverse model specific to our probe geometry to determine the scattering and absorption properties of the sclera. This method estimated the size and density of scatterers, absorbers-blood volume fraction, melanin concentration, oxygen saturation, and blood vessel size. The results illustrated that the initial clearing of sclera started 3 minutes after injecting glycerol to sclera. The sclera became completely transparent at 8 minutes and stayed clear for 10-15 minutes. During this time the choroid layer was visible through sclera. The clear sclera became less transparent over next 11 minutes and became completely opaque once we applied 0.9% saline to hydrate the sclera. These dehydration and hydration cycles were repeated 4 times for each eye and the results were consistent for all animal models. When glycerol was applied directly to sclera after the incision at the conjunctiva, the sclera became transparent instantaneously. For the secondary goal, the changes in optical properties of sclera were monitored during the dehydration and hydration cycles. The reduced scattering coefficient decreased when glycerol was injected and it further reduced with direct application. The scattering increased after re-hydration. We also measured the blood volume fraction, melanin concentration, oxygen saturation, and blood vessels diameter to calculate absorption coefficient with the DOS system. This study provided a novel way to identify morphological changes of sclera in addition to measuring changes in optical properties due to hyper osmotic agent. The changes in optical properties were consistent with the morphological changes in sclera during the dehydration and hydration cycles.

Video goniometry was used to study the angular dependence of scattering from tissues and test materials. Tissues and standard roughness samples (sandpaper) were placed vertically in front of a 543 nm He-Ne laser with the tissue surface normal at 45° from the incident beam. The scattered light patterns projected onto a screen that was photographed by a digital camera. The scatter pattern showed a specular peak centered at -45° which was described by a Henyey-Greenstein function. The pattern also presented a diffuse Lambertian pattern at 0° (normal to the tissue). The line between the peak specular and the peak Lambertian identified the scattering plane, despite any slight misalignment of the tissue. The analysis utilized a coordinate transform based on mathematics for mapping between a flat Mercator map and a spherical planetary surface. The system was used to study the surface roughness of muscle tissue samples (bovine striated muscle and chicken cardiac muscle).

Even though laser exposures of 1 s or less are non-isothermal events, researchers have had to rely upon the isothermal treatise of Arrhenius to describe the laser damage rate processes. To fully understand and model thermal damage from short exposure to laser irradiation we need to experimentally obtain the temperature history of exposed cells and correlate it with the cellular damage outcomes. We have recorded the thermal response of cultured retinal pigment epithelial cells in real-time with laser exposure using infrared imaging (thermography). These images were then overlaid with fluorescence images indicating cell death taken 1 hr post laser exposure. The image overlays allowed us to define the thermal history of cells at the boundary (threshold) of laser-induced death. We have found a correlation between the onset of cell death and the average temperature over the course of the laser exposure.

Near threshold retinal lesions were created in the eyes of non-human primate (NHP) subjects in the near infrared (NIR) wavelength range of 1100 to 1319 nm, with 80 to 100 ms laser exposures. Two new in vivo imagining techniques, Adaptive Optic enhanced-Spectral Domain Optical Coherence Tomography (AO-SDOCT) and Adaptive Optic enhanced confocal Scanning Laser Ophthalmoscope imagery (AOcSLO) were utilized to pinpoint areas of chronic damage within the retinal layers resulting from laser exposure. Advantages and limitations of each technology with regard to the study of laser retinal tissue interaction are highlighted.

A confocal imaging system mounted to a micrometer stage was used to image the thermal lens induced into a water filled Cain-cell artificial eye. A dual-beam pump-probe geometry was used to quantify the 633-nm visible wavelength probe beam's transient response when exposed to the near-infrared pump-beam source. The infrared laser radiation wavelengths tested were 1110, 1130, 1150 and 1318 nm for 1-s exposures to 450-mW of power. Analysis of video data revealed the amount of refractive shift, induced by the thermal lens, as a function of time. Data demonstrate how the formation and dissipation of the thermal lens follow a logarithmic excitation and exponential decay in time respectively. Confocal imaging showed that thermal lensing was strongest for the 1150-nm wavelength followed by 1130, 1318 and 1110-nm.

Near-infrared (NIR) laser exposures to the retina are affected by intraocular absorption, chromatic aberration and retinal absorption. We present the latest results of retinal exposure to wavelengths between 1.0 to 1.319 micrometers and show how the trends for long-pulse exposure are dramatically affected by intraocular absorption in the anterior portion of the eye.

An 810-nm diode laser system was developed to accelerate and improve the healing process in surgical scars. Using thermal post-conditioning, the laser system provides a localised moderate heating whose maximum temperature is controlled to prevent tissue damage and stimulate the heat shock proteins (HSP) synthesis. The 810-nm wavelength allows a deep penetration of the light into the dermis, without damaging the epidermis. The time along which surgical incision is treated (continuous wave) must therefore be selected carefully with respect to the temperature precision achieved within the heated volume. A top-hat profile is preferred to a Gaussian profile in order to ensure the skin surface temperature is homogenised, as is the temperature of the heated volume. The spot shape will depend on the medical indication. The treatment should be made safe and controlled by means of a safety strip containing an RFID chip which will transmit the various operating settings to the laser device. A clinical trial aims at evaluating the 810 nm-diode laser in surgical incisions, with only one laser treatment immediately after skin closure, of patients with Fitzpatrick skin types I to IV. Surgical incisions were divided into two fields, with only portions randomly selected receiving laser treatment. At the final scar analysis (12 months) of the pilot study, the treated portion scored significantly better for both surgeon (P = 0.046) and patients (P = 0.025). Further studies may be warranted to better understand the cellular mechanisms leading to Laser-Assisted Skin Healing (LASH).

Melanoma is a malignant tumor of melanocytes which are found predominantly in skin. Melanoma is one of the rarer types of skin cancer but causes the majority of skin cancer related deaths. The staging of malignant melanoma using Breslow thickness is important because of the relationship to survival rate after five years. Pulsed photothermal radiometry (PPTR) is based on the time-resolved acquisition of infrared (IR) emission from a sample after pulsed laser exposure. PPTR can be used to investigate the relationship between melanoma thickness and detected radiometric temperature using two-layer tissue phantoms. We used a Monte Carlo simulation to mimic light transport in melanoma and employed a three-dimensional heat transfer model to obtain simulated radiometric temperature increase and, in comparison, we also conducted PPTR experiments to confirm our simulation results. Simulation and experimental results show similar trends: thicker absorbing layers corresponding to deeper lesions produce slower radiometric temperature decays. A quantitative relationship exists between PPTR radiometric temperature decay time and thickness of the absorbing layer in tissue phantoms.

Non-contact temperature measurement and imaging instruments are widely used in studies of laser interaction with tissue. For reliable results, independent verification of the instruments abilities and limitations is necessary. Two common types of heat measuring instruments are the LiTaO₃ type II pyrometer and the microbolometer array thermal imager. This study found that when considering the Signal to Noise Ratio, the temporal resolution, and the spatial dependency of the temperature measured by the instrument the microbolometer was superior for measurements of incident beams of 5 mm diameter and all pulse frequencies investigated.

The determination of sensation thresholds has applications ranging from uses in the medical community such as neural pathway mapping and for the diagnosis of diabetic neuropathy, to potential uses in determining safety standards. This study sought to determine the sensation threshold, and the distribution of sensation probabilities, for pulse trains ranging from two 10 ms pulses to nine 10 ms pulses from 2.01 μm laser light incident on a human forearm and chest. Threshold was defined as the energy density that would elicit sensation 50% of the time (ED50). A method of levels approach was used in conjunction with a monovariate binary response model to determine the ED50. We determined the ED50 and also a distribution of threshold probabilities. Threshold was found to be largely dependant on total energy deposited for smaller pulse trains, and thus independent of the number of pulses. Total energy becomes less important as the number of pulses increases however, and a decrease in threshold was measured for a nine pulse train as compared to one through four pulse trains. Thus we have demonstrated that this method is a useful and easy way for determining sensation thresholds from a 2.01 μm laser for possible clinical use. We have also demonstrated that lower power lasers when pulsed can elicit sensation at comparable levels to higher power single pulse lasers.

It is widely recognized for the realization of the pre-estimated treatment effects that the knowledge about the optical properties of the target tissues used to understanding the prediction of propagation and distribution of light within tissues would suffer from the technical problem such as the kinetic changes of the optical properties in laser irradiation. In this study, the optical properties of normal and laser coagulated chicken breast tissues and porcine intervertebral disks, normal and laser ablation have been determined in vitro in the spectral range between 350 and 1000 nm. In addition, the optical properties of the normal and photodynamic therapy (PDT) treated tumor, Lewis lung carcinoma, tissues have been determined. Diffuse reflectance and total transmittance of the samples are measured using an integrating-sphere technique. From these experimental data, the absorption coefficients and the reduced scattering coefficients of the samples are determined employing an inverse adding-doubling method. Laser coagulations and ablations have clearly increased the reduced scattering coefficient and slightly reduced the absorption coefficient. PDT treatment has increased absorption and reduced scattering coefficient. It is our expectation that these data will provide fundamental understandings on laser irradiation interactions behavior with tissues. The changes of the optical properties should be accounted for while planning the therapeutic procedure for the realization of safe laser treatments.

We have studied to develop the new thermal angioplasty methodology, photo-thermo dynamic balloon angioplasty (PTDBA), which provides artery dilatation with short-term (<15s) and uniform heating through the balloon by the combination of the efficient laser driven heat generation and fluid perfusion. Thermal denaturation degree of the collagen in artery media may be the important factor to attain sufficient artery dilatation for the PTDBA. In order to predict the optimum heating condition i.e. the balloon temperature and heating duration, we investigated the thermal denaturation dynamics of artery collagen in ex vivo. The extracted fresh porcine carotid artery was used. The temperature-dependent light scattering property and mechanical property of the artery specimen were simultaneously measured during artery temperature rising by specially made setup to assess the denaturation of arterial collagen. The change rate of the backscattered light intensity from the artery specimen; I(T)/I₀ with 633nm was measured to evaluate the artery scattering property change with the thermal denaturation. The artery specimen was heated from 25°C to 80°C with constant temperature rising rate of 3°C/min. The measured I(T)/I₀ was suddenly increased over 48°C. This boundary temperature might be the initiation temperature of the arterial collagen denaturation. We defined the variation of the I(T)/I₀ as the collagen denaturation ratio, and calculated the reactive enthalpy by the chemical equilibrium theory. Since the calculated enthalpy was similar to the enthalpy in literature report, the variety of I(T)/I₀ during the temperature rising might be attributed to the collagen conformational change due to the denaturation. In terms of the artery internal force measurement, the artery force was decreased with increasing of the artery temperature up to 65°C (i.e. softening), and increased over 65°C (i.e. shrinkage). We confirmed that the changes of the backscattered light (at 633nm in wavelength) from the artery might represent the artery collagen thermal denaturation degree.

Recently, an extensive layer of intra-cellular signals was discovered that was previously undetected by genetic radar. It is now known that this layer consists primarily of a class of short noncoding RNA species that are referred to as microRNAs (miRNAs). MiRNAs regulate protein synthesis at the post-transcriptional level, and studies have shown that they are involved in many fundamental cellular processes. In this study, we hypothesized that miRNAs may be involved in cellular stress response mechanisms, and that cells exposed to thermal stress may exhibit a signature miRNA expression profile indicative of their functional involvement in such mechanisms. To test our hypothesis, human dermal fibroblasts were exposed to an established hyperthermic protocol, and the ensuing miRNA expression levels were evaluated 4 hr post-exposure using microRNA microarray gene chips. The microarray data shows that 123 miRNAs were differentially expressed in cells exposed to thermal stress. We collectively refer to these miRNAs as thermalregulated microRNAs (TRMs). Since miRNA research is in its infancy, it is interesting to note that only 27 of the 123 TRMs are currently annotated in the Sanger miRNA registry. Prior to publication, we plan to submit the remaining novel 96 miRNA gene sequences for proper naming. Computational and thermodynamic modeling algorithms were employed to identify putative mRNA targets for the TRMs, and these studies predict that TRMs regulate the mRNA expression of various proteins that are involved in the cellular stress response. Future empirical studies will be conducted to validate these theoretical predictions, and to further examine the specific role that TRMs play in the cellular stress response.

Modifications to our previously introduced system for laser microbeam cell surgery were carried out in the present work to match animal cells. These modifications included: 1- Using other laser system that used before, Excimer laser with 193 and 308 nm wavelengths. The used laser here, is He-Cd with low power and 441.5 nm wavelength in the visible region. 2- Instead of using pulsed laser, we used here CW He-Cd chopped by electrical chopper, which is synchronized with the mechanical motion of the mobile stage with step 40 microns, according to cell dimensions to avoid puncturing the same cell twice. The advantages of the modified here laser setup for gene transfer is: it is less damaging to the sensitive animal cell which has thin cell membrane. The present work aimed to: 1- Design a modified laser microbeam cell surgery, applicable to animal cells, such as fibroblast cells 2- To examine the efficiency of such system. 3- To assure gene transfer and its expression in the used cells. 4- To evaluate the ultra damages produced from using the laser beam as a modality for gene transfer. On the other wards, to introduce: safe, efficient and less damaging modality for gene transfer in animal cells. To achieve these goals, we applied the introduced here home-made laser setup with its synchronized parameters to introduce pBK-CMV phagemid, containing LacZ and neomycin resistance (neor )genes into BHK-21 fibroblast cell line. The results of the present work showed that: 1- Our modified laser microbeam cell surgery setup proved to be useful and efficient tool for gene transfer into fibroblast cells. 2- The presence and expression of LacZ gene was achieved using histochemical LacZ assay. 3- Selection of G418 antibiotic sensitivity assay confirmed the presence and expression towards stability of neor gene with time. 4- Presence of LacZ and neor genes in the genomic DNA of transfected fibroblast cells was indicated using PCR analysis. 5- Transmission electron microscopy indicated that, no ultradamages or changes for cell; membrane, organilles or any component of transfected fibroblast cell as a result of using laser microbeam compared with control cell.

In this study, depth resolved measurements of absorption profiles in the wavelength range of 800 nm with a bandwidth of 140 nm are demonstrated using high speed spectroscopic frequency domain OCT (SOCT). With proper calibration, SOCT is able to extract absolute, depth resolved absorption profiles over the whole wavelength range at once without the need of tuning and performing measurements at single wavelengths sequentially. In addition, high acquisition speed in excess of 20 kHz allows to measure absorption dynamics with 50 μs time resolution, which might be useful for the investigation of pharmacokinetics or pharmacodynamics. SOCT of ~600 μm thick single- and multilayered, weakly scattering phantoms with varying absorption in the range of 10-60 cm^-1, equivalent to blood absorption in capillaries, is presented. SOCT measurements are compared with those using a spectrometer in transmission mode. For Indocyanine Green (ICG), a dynamic absorption measurement is demonstrated.

Recently, femtosecond laser technology has been shown to be effective in the inactivation of non-pathogenic viruses. In this paper, we demonstrate for the first time that infectious numbers of pathogenic viruses such as Human Immunodeficiency Virus (HIV) can be reduced by irradiation with subpicosecond near infrared laser pulses at a moderate laser power density. By comparing the threshold laser power density for the inactivation of HIV with those of human red blood cells and mouse dendritic cells, we conclude that it is plausible to use the ultrashort pulsed laser to selectively inactivate blood-borne pathogens such as HIV while leaving the sensitive materials like human red blood cells unharmed. This finding has important implications in the development of a new laser technology for disinfection of viral pathogens in blood products and in the clinic.

An ultrasound-based technique capable of detection and spatio-temporal characterization of microbubbles induced in water by femtosecond laser is reported. A highly focused single-element ultrasound transducer was used both to detect passive acoustic emission of the microbubbles and to probe the microbubbles at different stage of their evolution. The location of origin and wall of the microbubble was assessed from temporal characteristics of the passive acoustic emissions and of the pulse-echo signals. The radius of the microbubble was estimated as the distance between the origin of the bubble and its wall. The ultrasound characterization of microbubbles induced by femtosecond pulses agreed well with theoretical predictions based on the well-known Rayleigh-based model of bubble behavior in liquid. The results of this study demonstrate that femtosecond laser-induced microbubbles with typical sizes of several tens of micrometers can be characterized by the developed ultrasound technique.

In laser ablation of biological tissues, tomography of the tissue surface is necessary for measurement of the crater depth and observation of the thermal damage of the tissue. Optical coherence tomography (OCT) is a very promising candidate for an in-situ observation of the tissue. We demonstrate here dynamic analysis of tissue laser ablation using a real-time OCT.

Cell mono-layers were irradiated with nanosecond laser pulses under two distinct scenarios: (a) with culturing medium positioning the beam waist at different stand-off distances γ and (b) without cell culturing medium, positioning the beam waist directly on top of the cell mono-layer. Damaged cells were marked with Trypan Blue, a vital cell marker. Three different zones of damage were identified: (1) a zone of complete cell clearance, surrounded by (2) a ring of dead cells marked with Trypan Blue and (3) the rest of the cell culture where the cells remain alive and viable. Different hydrodynamic mechanisms damage cells as it was shown by high speed video for γ=0 and comparison with time resolved imaging. The cell damage mechanism has its origin on the optical breakdown plasma formation. For the case with culturing medium, a combination of plasma formation and shear stresses are responsible for cell damage; wheras for the case without cell culturing medium, the plasma formation is the only mechanism of interaction between laser pulses and cells. The rapidly expanding plasma generates shock waves whose pressure is most likely responsible for the cell detachment observed.

In this paper, we present a model-based predictive control system that is capable of capturing physical and biological variations of laser-tissue interaction as well as heterogeneity in real-time during laser induced thermal therapy (LITT). Using a three-dimensional predictive bioheat transfer model, which is built based on regular magnetic resonance imaging (MRI) anatomic scan and driven by imaging data produced by real-time magnetic resonance temperature imaging (MRTI), the computational system provides a regirous real-time predictive control during surgical operation process. The unique feature of the this system is its ability for predictive control based on validated model with high precision in real-time, which is made possible by implementation of efficient parallel algorithms. The major components of the current computational systems involves real-time finite element solution of the bioheat transfer induced by laser-tissue interaction, solution module of real-time calibration problem, optimal laser source control, goal-oriented error estimation applied to the bioheat transfer equation, and state-of-the-art imaging process module to characterize the heterogeneous biological domain. The system was tested in vivo in a canine animal model in which an interstitial laser probe was placed in the prostate region and the desired treatment outcome in terms of ablation temperature and damage zone were achieved. Using the guidance of the predictive model driven by real-time MRTI data while applying the optimized laser heat source has the potential to provide unprecedented control over the treatment outcome for laser ablation.

We solve a transient one-dimensional inhomogeneous Bio-Heat equation on a semi-infinite isotropic domain. The external source was modeled after Beer's law of deposition; the penetration depth was left arbitrary. The theoretical model is tested against experimental whole-body irradiation data. Pennes' thermal model correctly modeled the initial surface temperature rise, but experiment diverged from theoretical predictions after 30 minutes of exposure. Mortality statistics from a limited irreversibility study provided another means of comparison. All three major quartiles describing irreversibility are to be found well within the divergent space, where theory and experimental data diverge. Also, the mortality statistics seem to converge onto the divergence point.

The optical property of biological skin is reconstructed from published experimental absorption data. A smooth chart of all relevant data is formed by splicing, interpolation and extrapolation methods. The regularized set of absorption data is transformed through Kramers-Krönig relations to yield a set of theoretical index of refraction for biological skin. The well known absorption characteristics of pure liquid water provide supplemental information for missing data. The Kramers-Krönig transformation is numerically realized through Discrete Fourier Transforms and enables the use of the Fast Fourier Transform (FFT) algorithm. A unique implementation of Richardson's extrapolation method reduced multivalued point sets containing experimental absorption data. Extrapolation techniques also aided in covering unavoidable gaps in experimental data.

Monte Carlo (MC) simulations are considered the "gold standard" for mathematical description of photon transport in tissue, but they can require large computation times. Therefore, it is important to develop simple and efficient methods for accelerating MC simulations, especially when a large "library" of related simulations is needed. A semi-analytical method involving MC simulations and a path-integral (PI) based scaling technique generated time-resolved reflectance curves from layered tissue models. First, a zero-absorption MC simulation was run for a tissue model with fixed scattering properties in each layer. Then, a closed-form expression for the average classical path of a photon in tissue was used to determine the percentage of time that the photon spent in each layer, to create a weighted Beer-Lambert factor to scale the time-resolved reflectance of the simulated zero-absorption tissue model. This method is a unique alternative to other scaling techniques in that it does not require the path length or number of collisions of each photon to be stored during the initial simulation. Effects of various layer thicknesses and absorption and scattering coefficients on the accuracy of the method will be discussed.

We present a numerical procedure using the PN-method to model light distributions in layered structures such as the epithelium. In contrast to previous studies of layered media using Monte Carlo methods and discrete ordinates, the PN-method provides the flexibility to not only vary tissue optical properties across layers but also allows one to vary the tissue light interaction without changes to the numerical method. This includes the collection of generalized Fokker-Planck equations used in forward scattering approximations. Example calculations are performed for a model of the head consisting of a skull layer, cerebrospinal fluid layer, and cortex layer and a model of a port wine stain consisting of epidermis, dermis, and vascular malformation layers. Results obtained with the PN-method are shown to agree with Monte Carlo simulation but are obtained in a fraction of the time needed for accurate Monte Carlo results.

Backscattered snake light, which has experienced exactly two large angle scattering, is taken into account together with the diffuse light to model light backscattering. This simple modification is shown to significantly improve the agreement in the radial profile of the intensity of the backscattering light between the model and Monte Carlo simulations. The applications of the analytical model in incoherent and coherent backscattering of light for subsurface reflectance spectroscopy are presented. A simple model for depolarization of backscattering light is also discussed.

The scattered light of tissues provides abundant information about the tissues properties. In this paper, light propagation in anisotropic scattering medium was investigated experimentally and theoretically. To study the influence of fibrous structure on the propagation of polarized light in anisotropic medium, the transmitted light from a section of dentin was measured. The measured polarization property of the scattered light was related to the polarization direction of the incident light. Cylindrical scatterer was utilized to model the scattering of microstructure in dentin. The experimental results are compared with the simulation results. The results demonstrated that the microstructure in anisotropic medium has effect on both propagation direction and polarization of scattered light. Understanding the effects of microscopic structure on the polarized light scattering will aid to develop polarization dependent optical detection methods in anisotropic medium.

Short duration (< 20 ms) pulses are desirable in patterned scanning laser photocoagulation to confine thermal damage to the photoreceptor layer, decrease overall treatment time and reduce pain. However, short exposures have a smaller therapeutic window (defined as the ratio of rupture threshold power to that of light coagulation). We have constructed a finite-element computational model of retinal photocoagulation to predict spatial damage and improve the therapeutic window. Model parameters were inferred from experimentally measured absorption characteristics of ocular tissues, as well as the thresholds of vaporization, coagulation, and retinal pigment epithelial (RPE) damage. Calculated lesion diameters showed good agreement with histological measurements over a wide range of pulse durations and powers.