Several non-thermal factors influence the primary and secondary effects of interstitial thermal treatments using various types of non-ionizing irradiation. Recognition and understanding of the influences of these various factors are important in choice of energy source, the configuration of the application instrument and the design of treatments.

Currently, several minimally invasive hyperthermic-based surgical technologies are available for the treatment of dysfunctional and neoplastic tissues in a variety of organ systems. These therapies involve a number of different modalities for delivering heat energy to the target tissue, including radiofrequency/microwave, conductive/convective, loop resection, and others. Despite differences in energy transfer and organ system treated, hyperthermic lesions often have a multiregional architecture with a central thermal fixation region, adjacent middle coagulative-type necrosis region, and outer transitional region of variable cell injury/death. The regional percentages of these components vary depending on the overall thermal history distribution across the lesion. The thermal-fixed region generally lacks a wound healing response, resists breakdown/tissue repair, and may elicit a localized foreign body-type reaction. The other two regions generally undergo wound healing/repair with scar formation. The features of thermal fixation are highlighted and explored through several histopathologic case vignettes.

A system for performing MRI-guided transurethral prostate thermal therapy has been developed. Ultrasound energy is delivered from a multi-element heating applicator incorporating single or dual-frequency planar transducers. The heating applicators produce a directional heating pattern, and have the capability to generate an arbitrary three-dimensional thermal damage pattern in tissue. The delivery system includes five independent channels, each capable of producing up to 50W of RF power. An MRI-compatible motor has also been developed to control the rotation of the heating applicator inside the bore of a clinical 1.5T MR scanner. The capability to perform quantitative thermometry during heating with these heating applicators has been evaluated in a thermal gel material (TGM) developed in our lab with tissue-mimicking ultrasound and thermal properties.

Hyperthermia and high temperature thermal therapy are currently used in the clinical treatment for a variety of cancers. Despite the increasing use of thermal therapies, heat treatments have not gained large-scale clinical acceptance, due in part to inconsistencies in controlling heat deposition in vivo and the lack of precise temperature measurement. Interstitial ultrasound applicators provide superior spatial control of power deposition and heating patterns compared to other interstitial techniques. Real-time MR temperature imaging (MRTI) provides thermal therapies with an accurate, non-invasive method for measuring temperature within the body during treatment. In this study, three MR-compatible water-cooled interstitial ultrasound applicators designs were developed and evaluated for dynamic angular control of the thermal dose to a target area. Two of the applicator designs utilize an ultrasound transducer separated into three individually powered sectors allowing the user to control heating deposition for the creation of odd size and shape thermal lesions. The third design utilizes a 90o sectored transducer that can be rotated to target the thermal treatment to a specified area. Comparisons and predictions of the in vivo performance of all applicators was examined with experiments in ex vivo tissue and simulations created by a biothermal model that incorporates changes in acoustic attenuation and perfusion as a function of thermal dose. Ex vivo experiments with real-time MRTI correlated well with results from the biothermal model. The results of this study bracket the feasibility and potential in vivo performance of the applicator designs for minimally invasive cancer treatment with MRTI.

The application of heat to intervertebral discs is being clinically investigated for the treatment of discogenic back pain. The purpose of this study was to develop and test the feasibility of small ultrasound applicators that can be endoscopically placed adjacent to the disc, and deliver heating energy into the disc without puncturing the annular wall. Prototype devices were fabricated using curvilinear transducers (2.5-3.5 mm wide x 10 mm long, 5.4 - 6.5 MHz) that produce a narrow penetrating beam extending along the length of the ultrasound element. The transducer was affixed to either a flexible or rigid delivery catheter, and enclosed within an asymmetric coupling balloon with water-cooling flow. Bench measurements demonstrated 35-60% acoustic efficiencies, high-power output capabilities, and lightly focused beam patterns. The heating characteristics of these devices were evaluated with ex vivo and in vivo experiments within lumbar and cervical spine segments from sheep models and human cadaveric spine. The applicators were positioned adjacent to the annular wall of the surgically exposed discs. Ultrasound energy was focused directly into the disc to avoid heating the vertebral bodies. Multi-point thermocouple probes were placed throughout the disc to characterize the resultant temperature distributions. These studies demonstrated that ultrasound energy from these applicators penetrated the annular wall of the disc, and produced thermal coagulative temperatures of >60-65°C as far as 10 mm into the tissue. This study also showed that lower power levels and temperatures delivered for 10 minutes can generate a cytotoxic thermal dose of t_43°C >240 min penetrating 5-10 mm from the annular wall.

Several studies have suggested that thermal therapy has a beneficial effect on degenerated intervertebral discs. Possible therapeutic mechanisms include collagen denaturation, cell ablation, and nerve tissue coagulation, however the precise mechanism or combination of mechanisms is unknown. To investigate the in vivo effects of thermal therapy on intervertebral discs using a murine model, a monopolar RF heating probe was developed and characterized. In addition, the effect size of several different thermal exposures was investigated by quantifying regions of cell death and collagen denaturation in rat discs. The heating probes were fabricated to have a 0.3mm outer diameter, 0.9mm exposed heating tip, and contain a thermocouple to monitor probe temperature. Using less than 2 Watts of RF energy produced high temperatures close to the probe and a steep radial temperature falloff. Five discs were treated at each of seven thermal exposures: 80°C for 10min, 80°C for 1min, 75°C for 5min, 62°C for 10min, 55°C for 15min, 48°C for 15min, and 48°C for 5min. A cell death region was observed in all treated discs and was significantly greater at the 80°C for 10min exposure than any of the lower exposures. Denaturation area was significantly greater at the 80°C for 10min exposure than at the four lowest temperature exposures. Denaturation was not observed in the 48°C exposures and was inconsistent in the 55°C and 62°C exposures. These results demonstrate that it is possible to limit and target the effects of thermal therapy to a portion of the murine disc using this RF probe.

Microsulis, in conjunction with the University of Bath have developed a set of novel microwave applicators for the ablation of soft tissues. These interstitial applicators have been designed for use in open surgical, laparoscopic and percutaneous settings and range in diameter from 2.4 to 7 mm. A 20 mm diameter flat faced interface applicator was developed as an adjunct to the open surgical interstitial applicator and has been applied to the treatment of surface breaking lesions in hepatobiliary surgery. Taken as a complete tool set the applicators are capable of treating a wide range of conditions in a safe and efficacious manner. The modality employs a radiated electromagnetic field at the allocated medical frequency of 2.45 GHz and powers between 30 and 150 Watts. Computer simulations, bench testing, safety and efficacy testing, ex-vivo and in-vivo work plus clinical trials have demonstrated that these systems are capable of generating large volumes of ablation in short times with favourable ablation geometries. Clinical studies have shown very low complication rates with minimal local recurrence. It is considered that this modality offers major advantages over currently marketed products. The technique is considered to be particularly safe as it is quick and there is no passage of current obviating the requirement for grounding pads. Since the microwave field operates primarily on water and all soft tissues with the exception of fat are made up of approximately 70% water the heating pattern is highly predictable making repeatability a key factor for this modality.

The large variance of survival in the treatment of large superficial tumors indicates that the efficacy of current therapies can be dramatically improved. Hyperthermia has shown significant enhancement of response when used in combination with chemotherapy and/or radiation. Control of temperature is a critical factor for treatment quality (and thus effectiveness), since the response of tumor and normal cells is significantly different over a range of just a few degrees (41-45°). For diffuse spreading tumors, microwave conformal arrays have been shown to be a sound solution to deposit the power necessary to reach the goal temperature throughout the targeted tissue. Continuous temperature monitoring is required for feedback control of power to compensate for physiologic (e.g. blood perfusion and dielectric properties) changes. Microwave radiometric thermometry has been proposed to complement individual fluoroptic probes to non-invasively map superficial and sub-surface temperatures. The challenge is to integrate the broadband antenna used for radiometric sensing with the high power antenna used for power deposition. A modified version of the dual concentric conductor antenna presented previously is optimized for such use. Several design challenges are presented including preventing unwanted radiating modes and thermal and electromagnetic coupling between the two antennas, and accommodating dielectric changes of the target tissue. Advanced 3D and planar 2D simulation software are used to achieve an initial optimized design, focused on maintaining appropriate radiation efficiency and pattern for both heating and radiometry antennas. A cutting edge automated measurement system has been realized to characterize the antennas in a tissue equivalent material and to confirm the simulation results. Finally, the guidelines for further development and improvement of this initial design are presented together with a preliminary implementation of the feedback program to be used to control the temperature distribution in variable, inhomogeneous tissue.

Laboratory experiments have shown that thermal enhancement of radiation response increases substantially for higher thermal dose (approaching 100 CEM43) and when hyperthermia and radiation are delivered simultaneously. Unfortunately, equipment capable of delivering uniform doses of heat and radiation simultaneously has not been available to test the clinical potential of this approach. We present recent progress on the clinical implementation of a system that combines the uniform heating capabilities of flexible printed circuit board microwave array applicators with an array of brachytherapy catheters held a fixed distance from the skin for uniform radiation of tissue <1.5 cm deep with a scanning high dose rate (HDR) brachytherapy source. The system is based on the Combination Applicator which consists of an array of up to 32 Dual Concentric Conductor (DCC) apertures driven at 915 MHz for heating tissue, coupled with an array of 1 cm spaced catheters for HDR therapy. Efforts to optimize the clinical interface and move from rectangular to more complex shape applicators that accommodate the entire disease in a larger number of patients are described. Improvements to the system for powering and controlling the applicator are also described. Radiation dosimetry and experimental performance results of a prototype 15 x 15 cm dual-purpose applicator demonstrate dose distributions with good homogeneity under large contoured surfaces typical of diffuse chestwall recurrence of breast carcinoma. Investigations of potential interaction between heat and brachytherapy components of a Combination Applicator demonstrate no perceptible perturbation of the heating field from an HDR source or leadwire, no perceptible effect of a scanning HDR source on fiberoptic thermometry, and <0.5% variation of radiation dose delivered through the CMA applicator. By applying heat and radiation simultaneously for maximum synergism of modalities, this dual therapy system should expand the number of patients that can benefit from effective thermoradiotherapy treatments.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Surgical treatments, including hepatic resection and liver transplantation are considered as the most effective treatment of HCC. However, less than 20% of HCC patients can be treated surgically because of: multi-focal diseases, proximity of tumor to key vascular or biliary structures and inadequate functional hepatic reserve related coexistent cirrhosis. In this unfortunate groups of patients various palliative treatments modalities are being performed to extend the time of survival and quality of life. These techniques include trans-catheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and Interstitial Thermal Therapy: laser-induced interstitial thermotherapy (LITT) and radio-frequency ablation (RFA).

The Thermage ThermaCool TC system is a non-ablative RF device designed to promote tissue tightening and contouring. The system delivers RF energy to a target area under the skin, with volumetric tissue heating in that area. While the amount of energy delivered to a patient can be controlled by ThermaCool system settings, the distribution of energy to the treatment area and underlying layers is variable from individual to individual due to differences in body composition. The present study investigated how local tissue impedance affects the amount of discomfort experienced by patients during RF energy delivery. Discomfort results from heat generation in the treatment area. By using features of the ThermaCool TC System, local impedance (impedance of the treatment area), bulk impedance (impedance of the underlying tissue layers), and total impedance (the sum of local and bulk impedance) were measured for 35 patients. For each patient, impedance measurements were compared to discomfort levels expressed during treatment. Analysis of whole body, local, and bulk impedance values indicate that the percent of total body impedance in the local treatment area contributes to discomfort levels expressed by patients during treatment.

At Duke University Medical Center, selective LABC patients were treated on a protocol using neoadjuvant Myocet/Paclitaxel (ChT) and HT. With the purpose of generating perfusion/permeability parametric maps and to use gadolinium (Gd) enhancement curves to score and predict response to neoadjuvant treatment, a study was designed to acquire 3 sets of DE-MRI images along the 4 cycles of combined ChT and HT. A T1-weighted three-dimensional fast gradient echo technique was used over 30 minutes following bolus injection of Gd-based contrast agent. Perfusion/permeability maps were generated by fitting the signal intensity to a double exponential curve that generates washin (WiP) and washout (WoP), parameters that are associated with the tumors vascularity/permeability and cellularity. Based on the values of the WiP, the tumors were divided in lowWI (WiP < 100), mediumWI (100 200). During the HT treatments temperatures in the breast were measured invasively via a catheter inserted under CT guidance. Although minimum sampled temperatures give a crude indication of the temperature distribution, several thermal dose metrics were calculated for each of the HT fractions (e.g. T90, T50, T10). As expected, tumors that were more vascularized (i.e. higher WiP) heated less than tumors with low WiP, a degree on average. The adjuvant treatment also changed the shape and inhomogeneity of the perfusion/permeability maps, with dramatic changes after the first fraction in responders. The correlation between the thermal metrics and pathological response will be discussed, as well as possible correlation with other tumor physiology parameters. In conclusion, the Gd-enhancement analysis of DE-MRI images is able to generate information related to the tumor vascularity, permeability and cellularity that can correlate with the tumor's response to the neoadjuvant treatment in general, and to HT in particular. Work supported by a grant from the NCI CA42745.

During δ-aminolevulinic acid (ALA) based Interstitial Photodynamic Therapy (IPDT) a high light fluence rate is present close to the source fibers. This might induce an unintentional tissue temperature increase of importance for the treatment outcome. In a previous study, we have observed, that the absorption in the tissue increases during the treatment. A system to measure the local tissue temperature at the source fibers during IPDT on tissue phantoms is presented. The temperature was measured by acquiring the fluorescence from small Cr³⁺-doped crystals attached to the tip of the illumination fiber used in an IPDT-system. The fluorescence of the Alexandrite crystal used is temperature dependent. A ratio of the intensity of the fluorescence was formed between two different wavelength bands in the red region. The system was calibrated by immersing the fibers in an Intralipid solution placed in a temperature controlled oven. Measurements were then performed by placing the fibers interstitially in a pork chop as a tissue phantom. Measurements were also performed superficially on skin on a volunteer. A treatment was conducted for 10 minutes, and the fluorescence was measured each minute during the illumination. The fluorescence yielded the temperature at the fiber tip through the calibration curve. The measurements indicate a temperature increase of a few degrees during the simulated treatment.

Lower back pain affects a large group of people worldwide and when in its early stages, has no viable interventional treatment. In order to avoid the eventuality of an invasive surgical procedure, which is further down the Care Pathway, an interventional treatment that is minimally invasive and arrests the patient's pain would be of tremendous clinical benefit. There is a hypothesis that if the basivertebral nerve in the vertebral body is defunctionalized, lower back pain may be lessened. To further investigate creating a means to provide localized thermal therapy, bench and animal studies were planned, but to help select the applicator configuration and placement, numerical modeling studies were undertaken. A 3D finite element model was utilized to predict the electric field pattern and power deposition pattern of radiofrequency (RF) based electrodes. Three types of tissues were modeled: 1) porcine (ex-vivo), ovine (in-vivo preclinical), and 3) human (ex-vivo, in-vivo). Two types of RF devices were simulated: 1) a pair of converging, hollow electrodes, and 2) an in-line pair of spaced-apart electrodes. Temperature distributions over time were plotted using the electric field results and the bioheat equation. Since the thermal and electrical properties of the vertebral bodies of porcine, ovine, and human tissue were not available, measurements were undertaken to capture these data to input into the model. The measurements of electrical and thermal properties of cancellous and cortical vertebral body were made over a range of temperatures. The simulation temperature results agreed with live animal and human cadaver studies. In addition, the lesion shapes predicted in the simulations matched CT and MRI studies done during the chronic ovine study, as well as histology results. In conclusion, the simulations aided in shaping and sizing the RF electrodes, as well as positioning them in the vertebral body structures to assure that the basivertebral nerve was ablated, but other neighboring structures such as the spinal cord and nerve roots were spared.

Pathologic involvement of the basivertebral nerve, an intraosseous vertebral nerve found in humans and most mammalian species, may play a role in some forms of back pain. This study was designed to assess the feasibility and effects of the percutaneous delivery of radiofrequency (RF) energy to thermally ablate the basivertebral nerve in the lumbar vertebrae of mature sheep. Using fluoroscopic guidance, a RF bipolar device was placed and a thermal dose delivered to lumbar vertebral bodies in sheep. Post-treatment assessment included multiple magnetic resonance imaging (MRI) techniques and computed tomography (CT). These data were analyzed and correlated to histopathology and morphometry findings to describe the cellular and boney structural changes resulting from the treatment. Imaging modalities MRI and CT can be implemented to non-invasively describe treatment region and volume, marrow cellular effects, and bone density alterations immediately following RF treatment and during convalescence. Such imaging can be utilized to assess treatment effects and refine the thermal dose to vertebral body volume ratio used in treatment planning. This information will be used to improve the therapeutic ratio and develop a treatment protocol for human applications.

Pathological involvement of the basivertebral nerve (BVN), an intraosseous vertebral nerve, may play a significant role in some forms of back pain. This study was designed to assess the feasibility and effects of thermal ablation of the lumbar basivertebral nerve in mature sheep. Sixteen adult female sheep weighing 65-80 kg were anesthetized and positioned for ventral recumbent surgery. Under fluoroscopic guidance, two bilarterally oposed 5mm active length rediofrequency (RF) electrodes (1.65mm diameter were perfutaneously placed in select lumbar vertebrae at a relative angle of 70 degrees with a 5 mm tip separation. The elctrodes were advanced to the region of the vertebral bodies which contained the BVN. A thermal dose of 95° C/720 seconds was administered. Animals were survived for 2, 14, 90, or 180 days post-treatment. Clinical, radiologic and pathologic investigations were performed to determine the effect of the heat on the BVN and associated tissues. Thermal damage to the basivertebral neurovascular bundle was characterized by early hemorrhage and necrosis, followed by inflammation and fibrosis. Although there wasa significant revascularization of the treated bone marow regions, there was no evidence of basivertebral nerve survival or regeneration regeneration. In addition to ablation of teh basivertebral nerovascular bundle, the areas receiving the greatest treatment demonstrated initial mild local osteolysis and demineralization of the vertebral body bone and regional depopulation of the vertebral bone marrow cellular elements. Significant bone remodeling in the affected areas had begun by 14 days post-treatment. Bone remodeling was characterized by conventional osteoblast proliferation, osteoid deposition, and mineralization. This study demonstrated the ability to accurately, reproducibly, and safely ablate the basivertebral nerve and neurovascular bundle in mature sheep using a fluoroscopically guided percutaneously delivered radiofrequency technique.

ETherm3 is a finite-element software suite for simulations of electrosurgery and RF thermal ablation processes. Program components cover the complete calculation process from mesh generation to solution analysis. The solutions employ three-dimensional conformal meshes to handle cluster probes and other asymmetric assemblies. The conformal-mesh approach is essential for high-accuracy surface integrals of net electrode currents. ETherm3 performs coupled calculations of RF electric fields in conductive dielectrics and thermal transport via dynamic solutions of the bioheat equation. The boundary-value RF field solution is updated periodically to reflect changes in material properties. ETherm3 features advanced material models with the option for arbitrary temperature variations of thermal and electrical conductivity, perfusion rate, and other quantities. The code handles irreversible changes by switching the material reference of individual elements at specified transition temperatures. ETherm3 is controlled through a versatile interpreter language to enable complex run sequences. The code can automatically maintain constant current or power, switch to different states in response to temperature or impedance information, and adjust parameters on the basis of user-supplied control functions. In this paper, we discuss the physical basis and novel features of the code suite and review application examples.

Ultrahigh resolution OCT using broadband light sources achieves improved axial image resolutions of ~2-3 um compared to standard 10 um resolution OCT used in current commercial instruments. High-speed OCT using Fourier/spectral domain detection enables dramatic increases in imaging speeds. 3D OCT retinal imaging is performed in human subjects using high-speed, ultrahigh resolution OCT, and the concept of an OCT fundus image is introduced. Three-dimensional data and high quality cross-sectional images of retinal pathologies are presented. These results show that 3D OCT may be used to improve coverage of the retina, precision of cross-sectional image registration, quality of cross-sectional images, and visualization of subtle changes in retinal topography. 3D OCT imaging and mapping promise to help elucidate the structural changes associated with retinal disease as well as to improve early diagnosis and monitoring of disease progression and response to treatment.

Microwave Endometrial Ablation (MEA) is a technique that can be used for the treatment of abnormal uterine bleeding. The procedure involves sweeping a specially designed microwave applicator throughout the uterine cavity to achieve an ideally uniform depth of tissue necrosis of between 5 and 6mm. We have performed a computer analysis of the MEA procedure in which finite element analysis was used to determine the SAR pattern around the applicator. This was followed by a Green Function based solution of the Bioheat equation to determine the resulting induced temperatures. The method developed is applicable to situations involving a moving microwave source, as used in MEA. The validity of the simulation was verified by measurements in a tissue phantom material using a purpose built applicator and a calibrated pulling device. From the calculated temperatures the depth of necrosis was assessed through integration of the resulting rates of cell death estimated using the Arrhenius equation. The Arrhenius parameters used were derived from published data on BHK cells. Good agreement was seen between the calculated depths of cell necrosis and those found in human in-vivo testing.

Thermal ablation is a minimally-invasive treatment option for benign prostatic hyperplasia (BPH) and localized prostate cancer. Accurate spatial control of thermal dose delivery is paramount to improving thermal therapy efficacy and avoiding post-treatment complications. We have recently developed three types of transurethral ultrasound applicators, each with different degrees of heating selectivity. These applicators have been evaluated in vivo in coordination with magnetic resonance temperature imaging, and demonstrated to accurately ablate specific regions of the canine prostate. A finite difference biothermal model of the three types of transurethral ultrasound applicators (sectored tubular, planar, and curvilinear transducer sections) was developed and used to further study the performance and heating capabilities of each these devices. The biothermal model is based on the Pennes bioheat equation. The acoustic power deposition pattern corresponding to each applicator type was calculated using the rectangular radiator approximation to the Raleigh Sommerfield diffraction integral. In this study, temperature and thermal dose profiles were calculated for different treatment schemes and target volumes, including single shot and angular scanning procedures. This study also demonstrated the ability of the applicators to conform the cytotoxic thermal dose distribution to a predefined target area. Simulated thermal profiles corresponded well with MR temperature images from previous in vivo experiments. Biothermal simulations presented in this study reinforce the potential of improved efficacy of transurethral ultrasound thermal therapy of prostatic disease.

Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain. Symptoms are manifested as impairment of motor, sensory, or psychic function with or without loss of consciousness or convulsive seizures. This paper presents an initial post-operative heat transfer analysis of surgery performed on a 41 year-old man with medically intractable Epilepsy. The surgery involved tumor removal and the resection of adjacent epileptogenic tissue. Electrocorticography was performed before resection. Cold saline was applied to the resulting interictal spike foci resulting in transient, complete cessation of spiking. A transient one dimensional semi-infinite finite element model of the surface of the brain was developed to simulate the surgery. An approximate temperature distribution of the perfused brain was developed by applying the bioheat equation. The model quantifies the surface heat flux reached in achieving seizure cessation to within an order of magnitude. Rat models have previously shown that the brain surface temperature range to rapidly terminate epileptogenic activity is 20-24°C. The developed model predicts that a constant heat flux of approximately -13,000W/m², applied at the surface of the human brain, would achieve a surface temperature in this range in approximately 3 seconds. A parametric study was subsequently performed to characterize the effects of brain metabolism and brain blood perfusion as a function of the determined heat flux. The results of these findings can be used as a first approximation in defining the specifications of a cooling device to suppress seizures in human models.

Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

The ablation rate of articular cartilage and fibrocartilage (meniscus), were quantified to examine wavelength and tissue-composition dependence of ablation efficiency for selected mid-infrared wavelengths. The wavelengths tested were 2.9 um (water dominant absorption), 6.1 (protein and water absorption) and 6.45 um (protein dominant absorption) generated by the Free Electron Laser (FEL) at Vanderbilt University. The measurement of tissue mass removal using a microbalance during laser ablation was conducted to determine the ablation rates of cartilage. The technique can be accurate over methods such as profilometer and histology sectioning where tissue surface and the crater morphology may be affected by tissue processing. The ablation efficiency was found to be dependent upon the wavelength. Both articular cartilage and meniscus (fibrocartilage) ablations at 6.1 um were more efficient than those at the other wavelengths evaluated. We observed the lowest ablation efficiency of both types of cartilage with the 6.45 um wavelength, possibly due to the reduction in water absorption at this wavelength in comparison to the other wavelengths that were evaluated.

One of the main problems during laser stimulation in human pain research is the risk of tissue damage caused by excessive heating of the skin. This risk has been reduced by using a laser beam with a flattop (or superGaussian) intensity profile, instead of the conventional Gaussian beam. A finite difference approximation to the heat conduction equation has been applied to model the temperature distribution in skin as a result of irradiation by flattop and Gaussian profile CO2 laser beams. The model predicts that a 15 mm diameter, 15 W, 100 ms CO2 laser pulse with an order 6 superGaussian profile produces a maximum temperature 6 oC less than a Gaussian beam with the same energy density. A superGaussian profile was created by passing a Gaussian beam through a pair of zinc selenide aspheric lenses which refract the more intense central region of the beam towards the less intense periphery. The profiles of the lenses were determined by geometrical optics. In human pain trials the superGaussian beam required more power than the Gaussian beam to reach sensory and pain thresholds.

As a major component of the connective tissues, collagen fibers are responsible for various physiological functions inside the body. They provide support for the skin, partial focusing through the cornea, and coordinate movements via tendons, ligaments, and cartilages. In many medical procedures, thermal reorganization of the collagen structure is inevitable or desired. Therefore, the optimization of the therapeutic values of these procedures requires the characterization of thermal changes to collagen fibers. In this presentation, we use multiphoton microscopy to achieve this task. We will show that second harmonic generation (SHG) microscopy can characterize the thermally altered states of collagen and that they have potentials to be used in imaging applications in vivo.

Large spherical ultrasound phased arrays are ideal for simulation studies of thermal therapy devices designed for noninvasive breast cancer treatments. In a spherical array, circular sources packed in a dense hexagonal arrangement facilitate the most efficient use of the available aperture. Circular sources are also preferred for simulations of large phased arrays because pressure fields are computed more rapidly for circular pistons than for any other transducer geometry. The computation time is further reduced for circular transducers with grid sectoring. With this approach, the grid of computed pressures is divided into several regions, and then grid sectoring applies more abscissas in regions where the pressure integral converges slowly and fewer abscissas where the integral converges rapidly. As a result, the peak value of the numerical error is roughly the same in each sector, so the maximum numerical error in the computed field is maintained while the computation time is significantly reduced. The grid sectoring approach is extended to three dimensions (3D) for pressure field calculations with spherical arrays. In 3D calculations, the sectors are represented by cones, and the intersections between the computational grid and these cones define the boundaries required for grid sectoring. When these cone structures are applied to spherical phased arrays, 3D grid sectoring calculations rapidly compute the pressure fields so that the time required for array design and evaluation is substantially reduced.