The purpose of these preliminary experiments was to calculate the activation energy and the frequency factor constants of the Arrhenius equation for prediction of the denaturation zone produced by laser interstitial thermotherapy in female breast tissue models. In a first step, pairs of parameters consisting of the activation energy (ΔE) and frequency factor (A) were calculated for different half denaturation times at 50°C and 60°C. Pairs of parameters were eliminated if the calculated time of denaturation at 70°C was excessively short (<0.1s). In a second step, denaturation was calculated over time for each remaining pair of parameters using temperature measurements performed during a laser heating experiment in ex-vivo porcine mammary chain tissue. The zone of denaturation in the tissue after laser heating was 2.0 cm x 3.5 cm. One pair of Arrhenius parameters was chosen whose denaturation plot showed no denaturation outside the experimentally-observed denaturation zone, 50% denaturation at the border of the experimental denaturation zone, and 100% denaturation within the experimental denaturation zone after 1200 seconds. The activation energy and frequency factor which best fit our experimental data were ΔE=3.02x105 J mol-1 and A=1.18x1044 s-1, respectively. These values fall within the general range given in the literature.
Purpose: the purpose of these experiments was to evaluate the temperature and predicted cell kill distribution during LITT of breast tissue phantoms at 940nm and compare with the results of previous experiments ar 830 nm and 980 nm. Material and Methods: A Dornier Medilas D Skinpulse 940 nm diode lase system coupled to a Dornier D-6111-T2 fiber (Dornier Surgical Products, Phoenix, AZ) was used to irradiate the porcine tissue three times at approximately 5 W for 10 minutes. Results: The initial rate of temperature increase at 940 nm for locations 5, 10, and 15 mm from the fiber axis ranged from 0.076 to 0.142 °C/s, 0.027 to 0.041 °C/s, and 0.008 to 0.013 °C/s, respectively, wile the maximum temperature increase ranged from 37.8 to 46.9 °C, 19.3 to 26.1 °C, 8.6 to 13.0 °C, respectively, temperature curves hed lower slopes at 940 nm than at 830 nm and 980 nm. the maximum temperature increase was higher at 940 nm than at 830 nm. Predicted area of 100% cell kill was approximately 2 cm by 2 cm Conclusion: Results of experiments at 940 nm were more comparable to those at 980 nm than at 830 nm.
Intractable glaucoma results from hindrances in the eyeball aqueous humor pathways that increase the intraocular pressure above normal physiological levels (over 20 mmHg). In this study porous PTFE membranes were made hydrophilic with a photochemical method that use ethyl alcohol and water for the chemical solution.
Experiments on the feasibility of x-ray monitoring of laser interstitial thermotherapy (LITT) of breast cancer are presented. Digital images of heated tissue phantoms (including fatty porcine tissue and polyacrylamide/acrylate hydrogel), obtained from an x-ray stereotactic biopsy system, were analyzed for changes in pixel intensity. Tissue phantoms were heated either by a 980 nm diode laser or by resistive heating elements in a custom-made chamber. Analysis was conducted by evaluating the changes in average pixel intensity of regions of interest. Image constancy and stability of the x-ray system were also investigated. Slight changes (less than 5%) dependent on the temperature of the tissue phantom were observed, while changes caused by heat- induced tissue displacement and/or shrinkage were more significant (greater than 10%).
The purpose of these experiments was to compare the temperature increase in ex-vivo porcine mammary chain tissue as a breast tissue model during interstitial laser irradiation with diode lasers emitting at 980 nm and 830 nm. Both wavelengths were delivered at 4.0 W for 10 minutes through a diffusing fiber inserted into ex-vivo porcine tissue. The temperature was measured with a set of 15 thermocouples placed 5, 10, and 15 mm from the fiber axis. The initial rate of temperature increase 5 mm away from the fiber tip was higher at 980 nm (0.12 to 0.20 degree(s)C/s) than at 830 nm (0.10 to 0.16 degree(s)C/s). At 10 mm and 15 mm (areas with less radiation), the rate was smaller than at 5 mm (less than 0.06 degree(s)C/s at 10 mm and less than 0.02 degree(s)C/s at 15 mm) for both wavelengths with no significant difference between the 980 nm and 830 nm radiation. The temperature increase at 5, 10 and 15 mm away from the fiber tip after 10 minutes of irradiation was higher at 980 nm (36 to 45 degree(s)C at 5 mm, 14 to 30 degree(s)C at 10 mm and 9 to 17 degree(s)C at 15 mm) than at 830 nm (27 to 33 degree(s)C at 5 mm, 11 to 17 degree(s)C at 10 mm and 8 to 9 degree(s)C at 15 mm) after 10 minutes. These results were found to be highly dependent on tissue composition (muscle vs. fatty tissue).
The surgical techniques proposed to restore accommodation past the onset of presbyopia can be categorized in two classes, those based of scleral expansion and those based on intraocular lens implantation and lens capsule refilling. This paper describes and discusses the different techniques and summarizes the results of clinical and experimental animal trials. Restoration of accommodation has been demonstrated by at least two different teams in non-human senile primates using modifications of the lens capsule refilling technique originally described by Julius Kessler in the late fifties. The advent of recent advances in microsurgery, devices, and injectable polymers are very promising and human clinical trials may soon be envisaged.
A tissue phantom for experimental studies in Laser Interstitial ThermoTherapy (LITT) for the treatment of small breast tumors was developed and evaluated. The tissue phantom consists of a polyacrylamide/acrylate hydrogel matrix containing various concentrations of an absorber (Nigrosin) and a scatterer (Intralipid 10% solution), allowing the optical properties to be varied in accordance to experimental need. Temperature measurements in the phantom were performed with a thermocouple array placed symmetrically around the fiber axis during laser irradiation for different output powers, treatment duration, and different concentrations of absorber. A 980 nm diode laser system was used in conjunction with an REM LightStic 360 diffusing tip fiber. The polyacrylamide/acrylate matrix tissue phantom remained stable during laser irradiation and produced reproducible results. The behavior of the temperature curves produced by the phantom during laser irradiation was similar to the behavior of the temperature curves in ex-vivo tissue. Therefore, this tissue phantom can be used as a model for the thermal response of tissue during laser interstitial thermotherapy. The phantom will be used as an experimental model to determine a set of optimum laser treatment parameters for laser interstitial thermotherapy of breast cancer.
Purpose: Laser interstitial thermotherapy is a promising minimally- invasive technique for the treatment of small cancers of the breast that are currently removed surgically lumpectomy. The purpose of this work was to analyze in situ temperature fields recorded with stainless-steel thermocoupled probes during experimental laser interstitial thermo-therapy (LITT).
Methods: Both a CW Nd:YAG laser system emitting 20W for 25 to 30s and a 980 nm diode laser emitting 10 to 20 W for up to 1200s delivered through a fiber-optic probe were used to create localized heating in fatty cadaver pig tissue and milk as phantoms. To quantify an artifact due to direct heating of the thermocouple probes by laser radiation, experiments were also performed in air, water and intralipid solution. The temperature field around the fiber-optic probe during laser irradiation was measured every 0.3 s or 1 s with an array of up to fifteen needle thermocoupled probes. The effect of light absorption by the thermocouples probes was quantified and the time-dependence of the temperature distribution was analyzed.
Results: After removal of the thermocouple artifact, the temperature was found to vary exponentially with time with a time constant of 600 to 700 s.
Conclusions:The time-dependence of the interstitial temperature can be modeled by exponential functions both during ex vivo and in vivo experiments.
To bring the current laboratory and feasibility studies to successful, focused clinical trials, several important considerations must be met. These include tumor selection, patient selection, treatment method, assessment of the treatment field, and short and long term clinical strategies.
KEYWORDS: Tissues, Breast, Temperature metrology, Breast cancer, Tissue optics, Heat therapy, In vivo imaging, Fiber optics, Fiber lasers, Laser therapeutics
Temperature increases and the resultant thermal field produced by the irradiation of ex vivo (porcine and human) and in vivo (porcine) tissue models appropriate to the treatment of human breast tissue using Nd:YAG (cw:60W) radiation delivered with an interstitial fiber optic probe were recorded with an array of fifteen 23 gauge needle thermocouple probes connected to a laboratory computer based data acquisition system. Using a stepwise decreasing power cycle to avoid tissue charring, acceptably symmetric thermal fields of repeatable volumetric dimensions were obtained. Reproducible thermal gradients and predictable tissue necrosis without carbonization could be induce din a three centimeter diameter region around the fiber probe during a single treatment lasting only 3 minutes. The time-dependence of the temperature rise of the thermocouples surrounding the LITT probe were quantitatively modeled with simple linear functions during the applied laser heating cycles.
Currently over 50 kinds of intraocular lenses (IOLs) are approved for patient use in the treatment of cataracts and ametropia. These lenses are manufactured from at least 2 kinds of silicones as well as several kinds of acrylic polymers including polyHEMA, Poly HOXEMA, a range of polymethacrylate and polyacrylate formulations. We sought to measure spectral transmission curves of a range of IOLS in the UV-visible and near IR spectral regions in order to better characterize their optical properties and to provide a baseline from which to assess their alteration following implantation over time. Consideration of how this may best be achieved are discussed. The variable ability of both explained IOLs and some samples from a range of manufacturers to block UV wavelengths is commented upon.
The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.
David Robinson, Jean-Marie Parel, Xochitl Gonzalez-Cirre, David Denham, Fabrice Manns, Peter Milne, Robert Schachner, Alan Herron, Jason Comander, Gerhard Hauptmann
The treatment of primary breast cancer in the last half century has progressively decreased in its disfiguring consequences while maintaining the same level of cure. Extending this philosophy beyond lumpectomy, we propose to treat small primary breast cancers by laser interstitial therapy with minimal possible cosmetic distortion. Our program to achieve that goal has made considerable progress in the preclinical instrument modification and development of physical, tissue, and live animal models. In anticipation of a clinical trial this report updates information presented in 1996.
Clinical investigations have suggested the utility of being able to form, in situ, thin lenticules over the exposed corneal surface from the photopolymerization of a semi-liquid collagen gel. In order to be better able to understand and ultimately control the use of this viscous material for investigations of both the biological stability of these collagen films and their potential in synthetic epikeratoplasty we have studied the photochemical properties of the material. In particular, we have investigated the possibility of using light in the visible wavelength range to initiate gelation of bulk collagen gels, the crosslinking process being effected by added photoinitiators.
Photorefractive keratomileusis procedures are currently being evaluated for both direct ablation of the human cornea and for the shaping of synthetic lenticules, with the ArF excimer laser offering the promise of reduced photochemical damage of underlying tissues due to the non-penetrative nature of 193 nm radiation. In order to better consider the possible effects of any secondary luminescence produced by the interaction of 193 nm radiation with these materials, an optical system based on a gated diode array spectrometer was constructed and used to record their fluorescence spectra at known laser fluences. A broadband fluorescence peak centered around 290-330 nm was observed upon irradiation of corneal buttons and collagen-based biopolymers. The optical efficiency of the fluorescence cell was calibrated by the use of a scattering material of known reflectivity allowing estimates of the fluorescence quantum yield of this process to be made.
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