Intravascular irradiation using Re-186 liquid-filled balloon catheters: correlation between experimental and theoretical studies.

PURPOSE: Optimization of intravascular radiation to reduce stenosis following coronary angioplasty requires the ability to predict the patterns of radiation dose distribution. This investigation evaluated the agreement between Monte Carlo simulations and experimental radiation dose measurements for a radioisotope liquid-filled balloon catheter in a tissue equivalent phantom. METHODS AND MATERIALS: Direct measurements of the radiation dose from Re-186 liquid-filled balloons were made using thermoluminescent dosimeters (TLDs) and radiochromic film. Monte Carlo simulations were carried out using the Monte Carlo N-Particle code system (MCNP4B). RESULTS: The Monte Carlo generated dose values agreed with the experimentally determined results within the statistical uncertainty. A slightly higher penetration was indicated by regression analysis for the TLD data relative to the MCNP4B prediction that may be due to experimental configuration anomalies. For this balloon catheter, approximately 55 mCi of Re-186 will deliver 15 Gy at a 0.5 mm depth in tissue equivalent material in 5 min. CONCLUSIONS: Correlation between experimentally measured dose values and Monte Carlo computation supports the position that MCNP4B simulations constitute a valuable tool for investigating various clinical therapy designs. The agreement between Monte Carlo calculations and experiments provide confidence in applying MCNP4B to more sophisticated geometries of interest, and other methods of intravascular radiation dose delivery.

Comparison of effectiveness of thermoluminescent crystals LiF:Mg,Ti, and LiF:Mg,Cu,P for clinical dosimetry.

This study compared the relative effectiveness of TLD crystals LiF:Mg,Ti (TLD-100) and LiF:Mg,Cu,P (TLD-700H) for clinical dosimetry, focusing on reproducibility, linearity, and energy response. Experimental results indicated that TLD-700H was superior to TLD-100 with regard to reproducibility, lack of supralinearity, and the absence of variation in TL signal with radiation quality. TLD-700H also had the additional advantages of higher sensitivity and immediate readability. The investigators conclude that this relatively new TLD crystal shows promising potential for clinical dosimetry.

Dose uniformity from a computerized three-dimensional tissue compensating system.

A verification of dose uniformity of the Huestis Compu-Former, a three dimensional megavoltage tissue compensator, is presented. Tissue compensators were built for three different anthropomorphic phantoms: a head and neck, a mantle, and a breast. Film densitometry was used to evaluate the effectiveness of the tissue compensators by comparing isodose curves generated for a compensated and an uncompensated field. Evaluation of the isodose distributions for the three regions confirmed the use of the Compu-Former as a reliable tissue compensating system.

A self-collimating convolution backprojection algorithm for optimizing dose distributions of I-125 prostate implants.

The algorithm presented here for optimizing brachytherapy dose distributions is based on the idea that the seed distribution can be modeled as an activity distribution determined analogously to gamma camera imaging. The peripheral dose to the tumor is converted to a set of uncollimated projection data that are then filtered and backprojected to produce an initial seed distribution. The actual doses resulting from the seed placement are used to correct the initial projection data for attenuation, scatter, and lack of collimation. The corrected projection data are backprojected a second time to yield the optimized but unconstrained seed distribution. Clinical constraints such as the number of different seed activities, the maximum seed activity, the minimum peripheral tumor dose, and the minimum percentage of the volume which receives less than a specified dose are then applied to the unconstrained solution. Through the entire process, the dose calculations are functions of source anisotropy, scatter, and attenuation. When applied to a set of elliptical contours, the algorithm produces elliptical peripheral dose isodose contours and reasonable dose volume histograms for a constrained solution. The results for actual patient prostate contours were not as good, primarily because of the difficulties encountered in dealing with the irregular geometry of the prostate. However, the algorithm shows promise for further research.

Effect of in vivo exposure to iodine-131 on the frequency and persistence of micronuclei in human lymphocytes.

The validity of the micronucleus test as a biomarker of chromosome damage in dividing mammalian cells is well established. This assay was used to study the response of peripheral lymphocytes of a 34-yr-old male patient following treatment with 131I ablative radiation therapy following a total thyroidectomy. Coincidentally, 8 mo before diagnosis, the patient had provided a blood sample for an in vitro study of micronucleus induction following exposure to graded doses of x-rays. The background frequency in the unexposed culture showed a mean count of 6.0 micronuclei per 1000 binucleated (first division) lymphocytes, while mean values of 18.5, 29.0, 41.0, 61.0 and 75.5 micronuclei/1000 cells were observed following x-ray doses of 5, 10, 15, 20, and 25 cGy, respectively. These data fit a nonthreshold, linear dose-response function (y = 2.78x + 3.71; r = .99). Eight months after the in vitro x-ray study, the subject was diagnosed with thyroid cancer. Surgery was performed, and 5 wk later the patient received 1.78 GBq (48 mCi) of 131I as adjuvant radiation therapy. Blood was drawn 11 d after the radiation treatment and at monthly intervals thereafter to analyze the frequency and persistence of micronuclei. The first posttreatment sample showed 35.5 micronuclei per 1000 binucleate cells. Based on the linear dose-response equation from the earlier study, the sixfold increase in micronucleus frequency suggests a dose to the peripheral blood of approximately 11 cGy. The cytogenetic dose estimate compares to approximately 30 cGy using a new model based on external whole-body counting data. Nine consecutive monthly samples have been analyzed to date. Although the micronucleus count has fluctuated (four- to sixfold above background), the frequency after 8 mo is equivalent to the first posttreatment sample. Data show that radiation-induced cellular lesions persist for months following relatively brief radiation exposure to a medical isotope. Results of this study support the conclusion that the lymphocyte micronucleus test is a rapid, sensitive, and perhaps quantitative biomarker of low-dose (< 25 cGy) radiation exposure.

Therapeutic responses of spontaneous canine malignancies to combinations of radiotherapy and hyperthermia.

The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy (60CO) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44 degrees C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4-5 hours in the other. Adjuvant hyperthermia resulted in a significant (p less than .05) increase in complete response rate, reduction in the frequency of non-responders, and increased persistent local control relative to radiotherapy alone. Hyperthermia increased the complete response rate regardless of histology, site, or volume and with the current sample size control was significantly (p less than .05) greater for sarcomas, tumors of the trunk and extremities, and those with volumes less than 10 cc. Quantitative clinical assessment of the acute response of skin and oral mucosa indicated that hyperthermia significantly enhanced these acute reactions, which required roughly twice the healing time observed with radiotherapy alone. Quantitative histologic scoring of changes seen between pre- and post-therapy skin biopsies indicated that a treatment induced decline in the frequency of dermal blood vessels, sebaceous glands, and hair follicles was enhanced by adjuvant hyperthermia, particularly in the late response evaluation interval. The probability of tumor control and adverse normal tissue responses correlated with several measures of thermal dose. Thermal doses in excess of 120 equivalent minutes at 43 degrees C correlated positively with increased skin reactions and negatively with the complete response rate, and these trends were usually evident during the animals' first treatment.

The modification of specific absorption rates in interstitial microwave hyperthermia via tissue-equivalent material bolus.

Patterns of specific absorption rates generated by interstitial, microwave antenna arrays must be experimentally ascertained and quantified to facilitate their clinical incorporation. Phantom studies involved the use of four single-gap, coaxial antennas oriented in a 2 cm square array. These dipoles were driven in phase by a microwave generator at a frequency of 915 MHz. The inherent limitations in modifying the specific absorption rate patterns were addressed with the addition of bolus to the phantom. These additions of Guy's muscle tissue-equivalent material were made either proximal or distal to the phantom proper. Experiments conducted in the presence and absence of tissue-equivalent material bolus showed the ability to achieve broader bands of 50% power deposition in certain bolus conditions. These heating patterns were sufficiently reproducible and predictable to warrant clinical application of the bolus addition. A through-and-through method of catheter implantation allowed for bolus addition when deemed necessary. Treatments with veterinary and human patients using the bolus method to modify heating patterns yielded augmented patterns of power deposition. The effective length of the antennas that would radiate efficiently was essentially broadened via introduction of a microwave-interacting medium. As a result of the tissue equivalent material's ability to absorb microwave power, it was necessary to interpose minimally-interactive styrofoam spacers to limit heat transfer effects at the tissue-bolus interfaces.

A technique for delivery of total body irradiation for bone marrow transplantation in adults and adolescents.

With the increasing use of bone marrow transplantation for cancer, total body irradiation is becoming a more commonplace procedure in many of the larger centers across the country. The technical difficulties in delivering homogenous doses of radiation to the whole body are significant and involve many factors such as creation of a homogeneous, "flat" beam of radiation, and dealing with variations in patient thickness and tissue homogeneity, particularly in the lung. In addition, techniques must be used to safely and efficiently deal with patients who are usually very ill and require long treatment times. Although there is often an advantage in terms of dosimetry to using an AP/PA treatment technique, many institutions use parallel opposed lateral beams because of equipment and facility limitations. A technique has been devised that enables total body irradation to be given by an AP/PA technique using equipment available in many radiotherapy departments. Patients are supported in an upright position during treatment by means of a modified harness attached to the ceiling of the treatment room. Lung compensators are fixed to individually fitted "vests," allowing the patient moderate amounts of movement during treatment while maintaining the position of the compensator relative to the lungs. Thermoluminiscent dosimeter (TLD) dose measurements in a phantom indicate that this system can deliver accurate and homogeneous doses to lung tissue, while allowing a good degree of patient comfort and safety during the long treatment times that are required.

Breast conservation radiation therapy technique for women with large breasts.

A technique is presented for the conservative irradiation of women with huge (size "EE") breasts. Patients are treated in a modified lateral decubitus position with an immobilization device. The technique is easily reproducible and allows favorable cosmetic outcome. The isodose plots for treatment with this technique are compared to treatment in standard fashion. We feel that this reproducible technique offers breast conserving therapy to women with large breasts, without poor cosmesis.

Incorporation of patient immobilization, tissue compensation and matchline junction technique for three-field breast treatment.

A protocol for the treatment of the intact breast was developed to maximize dose homogeneity and reproducibility. This protocol uses patient and breast immobilization, three-dimensional tissue compensators, and a technique for geometric matching of fields when the supraclavicular area is treated. A series of phantom measurements and analysis of patient port films was performed to evaluate dose homogeneity and reproducibility using this technique, and the potential adverse effect of loss of skin sparing from the immobilization device was investigated. Dose homogeneity throughout the phantom breast was within +/- 6% of the prescribed central axis dose, and homogeneity at the supraclavicular match line was +/- 10%. This represented a significant improvement over techniques not using tissue compensation or geometrically matched fields. Reproducibility of patient treatments was not significantly improved from previous non-immobilized treatment techniques, but there was no loss of skin sparing from the device, and other advantages of immobilization were observed. Details of the protocol are discussed together with changes that are currently being made to improve the results obtained thus far.

The distribution of power and heat produced by interstitial microwave antenna arrays: II. The role of antenna spacing and insertion depth.

The distribution of power and temperature generated by 915 MHz interstitial microwave antenna arrays was studied in static muscle-equivalent phantoms and both perfused and non-perfused canine thigh muscle. These arrays, which would form the geometric basis of larger volume implants, consisted of four parallel antennas oriented such that transverse to their long axes they formed the corners of a square. Arrays with 2 and 3 cm sides were compared at various depths of insertion where the nodes for all four antennas were coincident at the same depth. The position relative to the antenna nodes of the maximum power and highest temperature within the array volume varied with the depth of insertion of the antennas. Though power dropped rapidly distal to the nodes at all depths, a shift in the location of the maximum power proximal to the nodes resulted in an increase in the effective heating volume at certain insertion depths. For 2 cm array spacing the highest power and temperature were measured along the central axis of the array at all insertion depths. However, arrays using 3 cm spacing generated their maximum power adjacent to the antennas with only 50% of this level occurring along the central axis. When the temperature produced by 3 cm arrays was measured in phantoms midway through simulated 30-minute hyperthermia treatments, the effect of thermal conduction on the temperature distribution was evident. Though power was only 50% centrally, the highest temperatures occurred there. This same pattern of central heating occurred in perfused canine muscle demonstrating the importance of conductive and convective heat redistribution in reducing thermal gradients within the array volume.

The distribution of power and heat produced by interstitial microwave antenna arrays: I. Comparative phantom and canine studies.

To adequately plan and administer localized hyperthermia with interstitial microwave antennas, the thermal distribution patterns generated by such antennas must be characterized. This study evaluated the performance of single node 915 MHz antennas operating either alone or as a 2 cm square array of four parallel antennas using both muscle-equivalent phantoms and canine thigh muscle. Two types of measurements were compared. Specific absorption rate (SAR), where temperature increases resulting from short duration microwave pulses were used to define power distribution, and temperature gradients during simulated hyperthermia treatments. SAR measurements in phantoms were comparable to those obtained in non-perfused canine muscle demonstrating the usefulness of the phantom for these measurements. For a single antenna there was a rapid decrease in power radially which resulted in a steep thermal gradient at distances within 0.5 cm. However, the power generated by a four-antenna array was highest along its central axis and declined to approximately 50% near the antennas at the array periphery. Along the central axis of the array power decreased most rapidly distal to the antenna nodes. The distribution of temperature measured during simulated hyperthermia treatments in phantoms paralleled the SAR distribution and was comparable to the temperature gradient observed in perfused canine muscle, suggesting that phantoms could be used to predict temperature distributions in resting muscle tissue.

Specific absorption rates in simulated tissue media for a 10 x 10 cm 915-MHz waveguide applicator.

The use of hyperthermia in combination with radiotherapy is currently being investigated at many cancer treatment facilities. Several different types of heating modalities are presently being used and for each of these systems it is important to determine the power distributions of their hyperthermia applicators in tissue-equivalent phantoms. This information will be used for treatment planning, routine quality assurance, and acceptance testing as well as for comparison between these various modalities and systems. This report describes the power distribution characteristics of the Clini-Therm 10 x 10 cm 915-MHz waveguide applicator measured within muscle tissue phantom materials arranged in several clinically relevant treatment configurations. The net increase in temperature that resulted from 20-s pulses of microwave power was measured at various points within each phantom by the system's implantable fiberoptic temperature sensors. From these temperature measurements the distribution of power was calculated as specific absorption rates (SAR). The results are displayed as two-dimensional ISO-SAR maps which relate power levels throughout the irradiated volume to those obtained on the central axis of the applicator. When the applicator was in direct contact with the muscle phantom the highest SAR measured was 2 cm lateral to its central axis along the muscle surface. On the central axis approximately 50% of the power was attenuated by each centimeter of muscle material. The introduction of either fat, bone, or a water-filled pad between the applicator and the muscle altered the pattern of power distribution within the irradiated volume without substantially altering the relative distribution of power along the central axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Measured neutron and gamma spectra from californium-252 in a tissue-equivalent medium.

A method of experimentally obtaining both neutron and gamma-ray spectra in a scattering medium is described. The method utilizes a liquid-organic scintillator (NE-213) coupled with a pulse-shape discrimination circuit. This allows the separation of the neutron-induced pulse-height data from the gamma-ray pulse-height data. Using mathematical unfolding techniques, the two sets of pulse-height data were transformed to obtain the neutron and gamma-ray energy spectra. A small spherical detector was designed and constructed to reduce the errors incurred by attempting spectral measurements in a scattering medium. Demonstration of the utility of the system to obtain the neutron and gamma-ray spectra in a scattering medium was performed by characterizing the neutron and gamma-ray spectra at various sites about a 3.7-microgram (1.5 cm active length) californium-252 source in a tissue-equivalent medium.

An isocentric technique for treatment of carcinoma of the prostate in large patients.

An isocentric technique for treatment of carcinoma of the prostate of a large patient was investigated for a 4-MV linear accelerator. A split course, two four-field technique was found to deliver an appropriate high-dose zone while not exceeding tissue tolerances.

Generation of iso-TDF maps: considerations for radiation therapy planning.

The NSD (nominal standard dose) concept has been useful in therapy for comparing various radiation treatment schedules. More recently, TDF (time, dose, and fractionation) factors were introduced. By incorporating treatment schedules (time and fractionation) with isodose summations, TDFs can be determined throughout the patient contour, including tissue in and outside the tumor volume. For this purpose an isodose summation program was modified to generate iso-TDF maps based on the treatment schedule. For schedules in which all fields are not treated every day, recovery is not inhibited throughout the total treatment volume. It was necessary to reevaluate the concept of "recovery time" for tissues outside the tumor volume and to introduce a "threshold to inhibit recovery" model. Clinical examples assuming this recovery model are presented.