The use of cylindrical coordinates for treatment planning parameters of an elongated 192Ir source.

PURPOSE: The doses given to the intima, media, and adventitia are very crucial quantities in intravascular brachytherapy. To facilitate accurate computerized treatment planning calculations, we have determined dose distributions in away-and-along table format around an 192Ir wire source and developed pertinent dosimetric parameters in cylindrical coordinates. METHODS AND MATERIALS: The Monte Carlo method (MCNP4C code) was used to calculate the dose distributions for the AngioRad 192Ir wire source (model SL-77HS, Interventional Therapies). The calculations were carried out for photon, beta, and electron (conversion and Auger) contributions for radial distances from 0.03 to 2.0 cm with 0.01-cm increments, and up to 2.24 cm from the source center in the longitudinal direction with 0.04-cm resolution. Dose rate values are determined in away-and-along format (cylindrical coordinates) and then converted to spherical coordinate format. Dosimetric parameters, such as the geometry factor, G(r, theta), and anisotropy function, F(r, theta), are generated in both cylindrical (R, Z, phi) and spherical (r, theta, phi) coordinates. The use of a cylindrical coordinate system for treatment planning parameters is proposed as a more suitable approach for accurate calculations. RESULTS: The photon contribution to dose varies nearly inversely with radial distance (from the source center) along the perpendicular bisector with 0.199 x 10(-3) cGy U(-1) s(-1) (0.802 cGy Ci(-1) s(-1)) at 1 cm. The beta and electron contributions start at very high values of about 35.5 x 10(-3) cGy U(-1) s(-1) and 11.0 x 10(-3) cGy U(-1) s(-1), respectively, at 0.03 cm and fall off exponentially to negligible amount near 0.2 cm. The total dose rate at 0.2 cm is 1.428 x 10(-3) cGy U(-1) s(-1) (5.754 cGy Ci(-1) s(-1)). The radial dose function, g(R), is nearly unity between 0.2 cm and 2 cm. Due to the beta and electron dose contributions, g(R) increases steeply to 5.5 as radial distance decreases from 0.2 cm down to 0.03 cm. The F(R, Z) values are close to unity for the majority of the region of interest. In contrast, F(r, theta) experiences a steep rise as shallow angles are approached (closer to the source), related to the beta dose contributions. Accurate treatment planning calculations would be possible with linear interpolation of F(R, Z), but difficult with F(r, theta) in the spherical coordinate system and the original normalization point as recommended in the American Association of Physicists in Medicine Task Group 60 (AAPM TG-60) formalism. CONCLUSION: The AngioRad 192Ir wire source, model SL-77HS, was completely characterized dosimetrically using Monte Carlo methods. The use of cylindrical coordinates and a modified anisotropy function normalization point for dosimetric parameters of an elongated 192Ir source is more suitable for accurate computerized treatment planning calculations in intravascular brachytherapy.

Treatment planning dosimetric parameters for a (90)Y coil source used in intravascular brachytherapy.

BACKGROUND: (90)Y coil sources have been used in animal and clinical trials for treatment of restenosis in intravascular brachytherapy (IVBT). This study aims to determine the American Association of Physicists in Medicine (AAPM) Task Group-60 (TG-60) dosimetric quantities in regions surrounding the balloon wall for use in treatment planning computer systems. METHODS: The Monte Carlo method was used to determine the dose distribution, using MCNP4B2 code. The coil source was modeled by a hollow cylinder of 2.9 cm length centered in a balloon (2.5 mm diameter) filled with carbon dioxide (CO(2)) at 5 atm. Scoring voxels consisted of contiguous annular disk shells with 0.1 mm spacing in the radial direction and 0.2 mm spacing in the longitudinal direction. The scoring region ranges from the center of the source to 1.0 cm in the longitudinal direction, and from 0.13 to 1 cm in the radial direction. In the plane containing the source axis, the Monte Carlo-generated doses in rectilinear coordinates are converted to polar coordinates. RESULTS: The dose rate of the source is provided in both Cartesian and polar coordinates. The dose rate constant [D(r(0),theta(0))], anisotropy function [F(r,theta)], and radial dose function [g(r)] were generated from these values and listed in tabular format. At shallow angles and longer distances from the source center, large values of the anisotropy function resulted, deviating two orders of magnitude from unity. CONCLUSIONS The doses given to the intima, media, and adventitia are very crucial quantities in IVBT. The calculated TG-60 dosimetric quantities, used commonly in conventional brachytherapy applications, provide a means for the user to determine the three-dimensional dose surrounding the balloon catheter. These parameters can be used in future treatment planning system for IVBT. We also discuss the need to develop a new formalism specific to longer sources used in IVBT.

A new treatment planning formalism for catheter-based beta sources used in intravascular brachytherapy.

Intravascular brachytherapy (IVBT) is an emerging modality for the treatment of atherosclerotic lesions in the artery. As part of the refinement in this rapidly evolving modality of treatment, the current simplistic dosimetry approach based on a fixed-point prescription must be challenged by future rigorous dosimetry method employing image-based three-dimensional (3D) treatment planning. The goals of 3D IVBT treatment planning calculations include (1) achieving high accuracy in a slim cylindrical region of interest, (2) accounting for the edge effect around the source ends, and (3) supporting multiple dwell positions. The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for gamma sources, as well as short beta sources with lengths less than twice the beta particle range. However, for the elongated beta sources and/or seed trains with lengths greater than twice the beta range, a new formalism is required to handle their distinctly different dose characteristics. Specifically, these characteristics consist of (a) flat isodose curves in the central region, (b) steep dose gradient at the source ends, and (c) exponential dose fall-off in the radial direction. In this paper, we present a novel formalism that evolved from TG-60 in maintaining the dose rate as a product of four key quantities. We propose to employ cylindrical coordinates (R, Z, phi), which are more natural and suitable to the slim cylindrical shape of the volume of interest, as opposed to the spherical coordinate system (r, theta, phi) used in the TG-60 formalism. The four quantities used in this formalism include (1) the distribution factor, H(R, Z), (2) the modulation function, M(R, Z), (3) the transverse dose function, h(R), and (4) the reference dose rate at 2 mm along the perpendicular bisector, D(R0=2 mm, Z0=0). The first three are counterparts of the geometry factor, the anisotropy function and the radial dose function in the TG-60 formalism, respectively. The reference dose rate is identical to that recommended by TG-60. The distribution factor is intended to resemble the dose profile due to the spatial distribution of activity in the elongated beta source, and it is a modified Fermi-Dirac function in mathematical form. The utility of this formalism also includes the slow-varying nature of the modulation function, allowing for more accurate treatment planning calculations based on interpolation. The transverse dose function describes the exponential fall-off of the dose in the radial direction, and an exponential or a polynomial can fit it. Simultaneously, the decoupling nature of these dose-related quantities facilitates image-based 3D treatment planning calculations for long beta sources used in IVBT. The new formalism also supports the dosimetry involving multiple dwell positions required for lesions longer than the source length. An example of the utilization of this formalism is illustrated for a 90Y coil source in a carbon dioxide-filled balloon. The pertinent dosimetric parameters were generated and tabulated for future use.

Ytterbium-169: a promising new radionuclide for intravascular brachytherapy.

PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.02

Effect of stent on radiation dosimetry in an in-stent restenosis model.

PURPOSE: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials. METHODS: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent. RESULTS: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources. CONCLUSIONS: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

125I eye plaque dose distribution including penumbra characteristics.

The two main purposes of this work are (1) to determine the penumbra characteristics for 125I eye plaque and the relative influence of the plaque and eye-air interface on the dose distribution, and (2) to initiate development of a treatment planning algorithm for clinical dose calculations. Dose was measured in a newly designed solid water eye phantom for an 125I (6711) seed at the center of a 20 mm COMS eye plaque using thermoluminescent dosimeter (TLD) "cubes" and "minichips" inside and outside the eye, in the longitudinal and transverse central planes. TLD cubes were used in most locations, except for short distances from the seed and in the penumbra region. In the presence of both the plaque and the eye-air interface, the dose along the central axis was found to be reduced by 10% at 1 cm and up to 20% at 2.5 cm, relative to the bulk homogeneous phantom case. In addition, the overall dose reduction was greater for larger off-axis coordinates at a given depth. The penumbra characteristics due to the lip collimation were quantified, particularly the dependence of penumbra center and width on depth. Only small differences were observed between the profiles in the transverse and longitudinal planes. In the bulk geometry (without the eye-air interface), the dose reduction due to the presence of the plaque alone was found to be 7% at a depth of 2.5 cm. The additional reduction of 13% observed, with the presence of eye-air interface (20% combined), can be attributed to the lack of backscattering from the air in front of the eye. The dose-reduction effect due to the anterior air interface alone became unnoticeable at a depth of 1.1 cm (1.5 cm from the eye-air interface). An analytic fit to measured data was developed for clinical dose calculations for a centrally loaded seed. The central axis values of the dose rates multiplied by distance squared, Dr2, were fitted with a double exponential function of depth. The off-axis profile of Dr2, at a given depth, was parametrized by a modified Fermi-Dirac function to model both the penumbra characteristics due the plaque lip collimation and the effect of oblique filtration by silastic.

Monte Carlo dosimetry for 125I and 60Co in eye plaque therapy.

Monte Carlo calculations of radiation dosimetry using MORSE code are performed for 125I and 60Co point sources in a cylindrical head phantom that simulates the geometry of eye plaque therapy for choroidal melanoma. We obtain the dose variation in the eye at submillimeter intervals over distances as close as 1 mm and up to 2.5 cm from the source. The calculations for 125I are performed for the phantom media of water, protein, and a homogenized protein-water mixture simulating the composition of the eye. Relative dose functions for 125I for these phantom media are fitted to second-degree polynomials. Agreement is found with published results. The relative dose function for 60Co at eye position in the water head phantom is fitted to a third-degree polynomial and compared with that for 60Co at the center of a large water sphere. A boundary effect due to the head phantom-air interface on the dose distribution for 60Co is demonstrated. The dose falloff with distance is faster for the eye geometry compared with the bulk geometry. We also show that the relative dose distributions within the tumor are comparable for 125I and 60Co by comparing their relative dose functions. This result is consistent with the success of clinical trials of large melanoma treatments with 125I plaques.

Coexistence of pituitary adrenocorticotropin-dependent Cushing's syndrome with a solitary adrenal adenoma.

A 45-yr-old woman presented with a 2-hr history of Cushing's syndrome. Baseline cortisol and ACTH levels were elevated and lacked a normal circadian rhythm. Dynamic testing of her pituitary-adrenal function revealed positive responses to metyrapone and synthetic ACTH and suppression with high doses of dexamethasone. The finding of asymmetrical adrenal uptake of 6-[131I]methyl-19-nor-cholesterol and a tumor image in the right adrenal on venography led to the preoperative diagnosis of pituitary ACTH-dependent adrenal hyperfunction coexisting with a right adrenal adenoma. Surgical resection of the right adrenal demonstrated a solitary 39-g nodule, 4 cm in diameter. There were no additional nodules present in the surrounding cortex. When incubated in vitro, both the adenoma and the surrounding tissue were functional and responsive to ACTH. This was in contrast to the lack of response to ACTH in vitro of similar tissues removed from two other patients with ACTH-independent adrenal adenomas. We suggest that this case represents a transition between pituitary ACTH-dependent bilateral adrenocortical hyperfunction and solitary adrenal adenoma.

Sustained remission of Cushing's disease with mitotane and pituitary irradiation.

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest.

Suppression of insulin secretion by protein deprivation in obesity.

1) Protein restricted diets decrease basal plasma insulin levels in obesity. 2) This effect occurs even in the presence of sufficient calories to maintain body weight and while the diet is high in carbohydrate. 3) The decrease in insulin is accompanied by a fall in plasma glucose and in the I/G ratio, suggesting an increase in insulin sensitivity. 4) Excessive protein intake, in addition to carbohydrate, may play a role in the pathogenesis of the hyperinsulinemia and insulin resistance found in obesity.

Radioimmunoassay of human parathyroid hormone in serum.

A new radioimmunoassay for human parathyroid hormone (PTH) in serum, which can measure the hormone present in 94% of the normal sera tested, is described. It is based on the ability of human PTH to compete with (131)I-labeled bovine PTH for binding to an antiserum directed against porcine PTH. This antiserum distinguishes between human PTH extracted from parathyroid adenomata and that present in hyperparathyroid sera. Evidence is given to suggest that this is due to immunochemical changes in the hormone extracted from adenomata and not to immunochemical heterogeneity of the hormone present in serum. Physiologic data supporting the validity and specificity of the assay are presented. Induced episodes of hypercalcemia and hypocalcemia resulted in appropriate responses in serum immunoreactive PTH (IPTH) in normal subjects and in patients with Paget's disease of bone. In normals, there was a progressive increase in serum IPTH in the late afternoon and evening, suggesting a diurnal secretory rhythm. A negative correlation was found between the serum calcium and serum IPTH over the normal range of serum calcium values; a positive correlation was found between these variables in patients with primary hyperparathyroidism. There was apparent overlap between serum IPTH values in normal subjects and patients with primary hyperparathyroidism, but formal discriminate analysis of values for serum calcium and IPTH demonstrated separation of these two groups, without overlap.

Native human parathyroid hormone: an immunochemical investigation.

We have produced an antiserum to porcine parathyroid hormone (PTH) which distinguishes between the PTH in human hyperparathyroid serum and that in extracts of parathyroid adenomata. The PTH secreted into the medium by parathyroid adenoma slices in culture reacts with this antiserum in the same way as the PTH in human hyperparathyroid serum, but extraction of the same serum by a conventional procedure used for the extraction of glandular tissue converts the serum hormone to a species which reacts more like hormone extracted from adenomata. The results suggest that we have immunologically identified a native molecular species of PTH, that the antiserum used recognizes primarily this species in human hyperparathyroid serum, and that the PTH extracted from parathyroid adenomata is immuno-chemically altered.