A new approach to film dosimetry for high-energy photon beams using organic plastic scintillators.

This study is concerned with dose measurement of photon beams, both dynamic and static, by using x-ray film. As discussed in our last study (Burch et al 1997, Yeo et al 1997), x-ray film, as an integrating dosimeter, can be an ideal candidate if the over-response problem to low-energy photons (energies below 400 keV) is solved. In summary, the problem of the over-response can be explained as follows. Because the mass energy absorption coefficient of x-ray film increases as photon energy decreases, softening of the photon spectra with depth in a phantom makes the extent of film over-response a function of phantom depth (Burch et al 1997, Yeo et al 1997). Film dosimetry is based upon (a) calibration of the film response (i.e. optical density) at some specific depth in a phantom and (b) conversion of the film density which can cover whole depths in a phantom to dose by using the calibration curve. In megavoltage dosimetry, this normally causes over-response in doses at depths greater than the calibration depth.

A new approach to film dosimetry for high energy photon beams: lateral scatter filtering.

A method of film dosimetry for high energy photon beams is proposed which reduces the required film calibration exposures to a set of films obtained for a small radiation field size and shallow depth (6 cm x 6 cm at 5 cm depth). It involves modification of a compression type polystyrene film phantom to include thin lead foils parallel to the vertical film plane at approximately 1 cm from both sides of the film emulsion. The foils act as high atomic number filters which remove low energy Compton scatter photons that otherwise would cause the film sensitivity to change with field size and depth. The proposed method is best described as "lateral scatter filtering." To validate the proposed method, central axis depth doses and isodose curves for a 4 MV photon beam were determined from films exposed within the modified phantom and the results compared with ionization chamber measurements. When no lateral filtering was used, for field sizes of 6 cm x 6 cm and 25 cm x 25 cm, this comparison demonstrated up to a 65% difference between film and ionization chamber central axis depth dose measurements. When using the lateral scatter filtering technique, less than a 4% difference was observed for these field sizes.

Measurement of 6-MV X-ray surface dose when topical agents are applied prior to external beam irradiation.

PURPOSE: Radiation therapy patients are typically warned not to apply lotions, deodorants, or powders to the skin within the treatment area because of the possible increase in surface dose due primarily to a bolus effect. This study investigates the effect of 15 products, with and without high atomic number components, on surface dose. METHODS AND MATERIALS: A Markus-type parallel plate ionization chamber in a polystyrene phantom was used to measure surface doses for normal applications of the products for a small (5 x 5-cm2) and a large (25 x 25-cm2) field size. RESULTS: The greatest surface dose increase for any product was 5.4% (21.8-27.2%) of the d(max) dose for the small field and 1.0% (43.6-44.6%) for the large field. Products with high-atomic-number components did not increase the surface dose relative to radiation therapy specialty products. CONCLUSION: No large increase in surface dose was detected with a normal application of the products. However, the possibility exists that an increase in skin reaction may occur owing to chemical irritants in the applied product.

A filtration method for improving film dosimetry in photon radiation therapy.

Successful radiotherapy requires accurate dosimetry for treatment verification. Existing dosimeters such as ion chambers, TLD, and diodes have drawbacks such as relatively long measurement time and poor spatial resolution. These disadvantages become serious problems for dynamic-wedged beams. Thus the clinical use of dynamic wedges requires an improved dosimetry method. X-ray film may serve this purpose. However, x-ray film is not clinically accepted as a dosimeter for photon beams, because it overresponds to photons with energies below about 400 keV. This paper presents and develops a method which was initially proposed by Burch to improve the dose response of x-ray film in a phantom. The method is based on placing high-atomic number foils next to the film. The foils are used as filters to preferentially remove low-energy photons. The optimal film and filter configuration in a phantom was determined using a mathematical scheme derived in this study and a Monte Carlo technique (ITS code). The optimal configuration thus determined is as follows: the filter-to-film distance of 6 mm and the filter thickness of 0.15 mm for percent depth-dose measurement; the distance of 1 cm and the thickness of 0.25 mm for off-axis (dose) ratio measurement. The configuration was then tested with photon beams from a 4 MV linac. The test result indicates that the in-phantom dose distribution based on the optimal configuration agrees well with those measured by ion chambers.

Radiation-induced early pulmonary endothelial ectoenzyme dysfunction in vivo: effect of indomethacin.

We investigated the early effects of radiation on pulmonary endothelial function in vivo 7-8 hr after exposure of rabbits to a single dose of 30 Gy to the chest. Utilizing multiple indicator-dilution techniques, we measured rates and kinetics of hydrolysis of the synthetic substrates [3H]benzoyl-Phe-Ala-Pro (BPAP) and [14C]benzoyl-Ala-Gly-Pro (BAGP) by endothelial-bound angiotensin-converting enzyme (ACE) and of 5'[14C]-AMP by endothelial-bound 5'-nucleotidase (NCT) and binding of the synthetic ACE inhibitor [3H]RAC-X-65 during a single transpulmonary passage in anesthetized, artificially ventilated, open-chest rabbits in which both systemic and pulmonary circulations were fully supported by an extracorporeal pump. We have shown that these techniques and the use of the aforementioned probes provide reliable information on pulmonary endothelial function in vivo. Radiation to the chest produced endothelial ectoenzyme dysfunction, as reflected in altered available perfused capillary surface area and altered enzyme kinetics of all probes (decreases in substrate hydrolysis, inhibitor binding, first- and second-order kinetic constants) over a wide range of pulmonary blood flow values (reflecting approximately 60-200% of normal cardiac output). Indomethacin prevented most of these alterations in partially as well as fully recruited lungs. We conclude that impairment of endothelial ectoenzyme activity is an early event in the pathogenesis of radiation-induced lung damage, which occurs independently of hemodynamic influences and may involve synthesis of arachidonic acid metabolites.

Assay of pulmonary microvascular endothelial angiotensin-converting enzyme in vivo: comparison of three probes.

We monitored the activity of pulmonary microvascular endothelial-bound angiotensin-converting enzyme (ACE) in vivo by means of multiple indicator-dilution-type techniques, utilizing three different probes: the hydrolysis of two substrates, [3H]-benzoyl-Phe-Ala-Pro (BPAP) and [14C]benzoyl-Ala-Gly-Pro (BAGP), and the binding of the inhibitor [3H]RAC-X-65 (RAC), all measured during a single transpulmonary passage in anesthetized rabbits, placed on total heart bypass, so that both systemic and pulmonary circulations were fully supported by means of a two-channel extracorporeal pump. Experiments were performed at pulmonary blood flows (Qb) of 250, 400, 560, and 800 ml/min in control or indomethacin-pretreated rabbits. ACE activity was also compared to that of pulmonary microvascular endothelial-bound 5'-nucleotidase, by measuring the dephosphorylation of its natural substrate 5'-[14C]AMP. We calculated substrate utilization, mean lung transit time (t), and volume of distribution (i.e., central blood volume) of all substrates, as well as inhibitor binding. We also calculated Amax/Km and Bmax products of enzyme mass and kinetic constants for substrates and inhibitor, respectively. As Qb increased, Amax/Km values for all three substrates and Bmax increased linearly, indicating microvascular recruitment. In experiments in which either BPAP and 5'-AMP metabolism or BAGP metabolism and RAC binding were studied concomitantly, a linear relationship was observed between Qb-induced changes in Amax/Km values of BPAP vs 5'-AMP as well as in Amax/Km of BAGP vs Bmax of RAC. Similarly, increasing Qb increased central blood volume and decreased t. Indomethacin had no effect on most of the hemodynamic or enzyme parameters measured. We conclude that in vivo assays of ACE proceed as predicted by Michaelis-Menten kinetics and offer insights into pulmonary endothelial pathophysiology.

Radiation-induced alterations in angiotensin converting enzyme activity in cultured bovine pulmonary arterial endothelial cell monolayers.

Bovine pulmonary arterial endothelial cells (BPAE) were exposed to a single dose 0, 5, 10, 20, or 30 Gy, in culture. Angiotensin converting enzyme (ACE) activity was determined in confluent monolayers, under first-order reaction conditions, at 6, 24, 48, and 96 hr after treatment, using [3H]benzoyl-Phe-Ala-Pro as substrate. Irradiation decreased the number of viable endothelial cells in a dose- and time-dependent manner, beginning at 24 hr after 5 Gy and reaching a maximum effect (21% survival) at 96 hr after 30 Gy. Total amount of protein per monolayer decreased during the same time intervals, whereas protein content per cell rose, signifying a radiation-induced hypertrophy of viable cells. When expressed per million surviving cells, ACE activity increased in a time- and dose-dependent manner, beginning at 24 hr after 5 Gy and reaching a maximum fourfold increase at 96 hr after 30 Gy. However, when expressed per culture well, ACE activity decreased in a time- and radiation-dependent manner. These results suggest that although at the lowest radiation dose (5 Gy), the increase in ACE activity per cell compensated for the enzymatic activity lost due to extensive cell death, at higher doses (10, 20, and 30 Gy), the increase in ACE activity per cell could not keep up with the decrease in the number of viable endothelial cells, leading to an overall decrease in ACE activity per culture well.

Generation of dose calculation data tables using cubic spline interpolation.

In order to calculate treatment machine settings for a teletherapy machine (e.g., time or monitor units), tables are usually used for variables such as output factor, TMR, percent depth dose. The tables are often generated from data collected at a few points. A linear interpolation is usually used to generate values between the measured points. This can introduce errors as great as 2% between the calculated and actual data points. Using a mathematical software package a computer can generate smooth, accurate curves that agree with measured values to within a few tenths of a percent. This method is not an averaging type of procedure by which a certain function is chosen and parameters are adjusted to force the function to fit the data as closely as possible, but rather is a procedure that fits curves exactly through the measured data points.

Early effects of ionizing radiation on pulmonary endothelial angiotensin-converting enzyme and 5'-nucleotidase, in vivo.

We investigated the early phase of pulmonary endothelial injury in rabbits exposed to a single dose (30 Gy) of ionizing radiation to the chest, by measuring endothelium-bound ectoenzyme activities. Utilizing multiple indicator-dilution techniques, the metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) and [14C]5'-AMP by angiotensin-converting enzyme (ACE) and 5'-nucleotidase (NCT), respectively, was studied during a single transpulmonary passage in conscious, chronically catheterized rabbits. From these data, the apparent kinetic constants Km and Amax were calculated. A significant (p less than 0.05) decrease in the metabolism of trace amounts of BPAP and 5'-AMP was observed at 2, 24, and 48 hr after irradiation. A similar decrease in the apparent first order rate constant (Amax/Km) of ACE was observed at 2 hr, but returned to control levels by 24 and 48 hr after irradiation. Apparent Km values of ACE for BPAP and NCT for 5'-AMP were elevated at 2, 24, and 48 hr post-treatment, whereas Amax (product of enzyme mass and the constant of product formation, kcat) of ACE was elevated at 2 and 24 hr but not at 48 hr, and Amax for NCT was elevated at 2 hr post-treatment only. Significant decreases in mean arterial blood pressure and pulmonary blood flow (Qb) at 2 hr post-treatment, and increases in Qb at 24 and 48 hr post-treatment were also recorded. No changes in endothelial structure were observed 2 hr after irradiation at the light or electron microscope level. We conclude that the early phase of radiation-induced lung injury includes changes in endothelial enzyme function in the absence of structural damage, as reflected in an apparent decrease in affinity of ACE and NCT for their substrates, allowing for the possibility that hemodynamic disturbances or their sequalae could also have contributed to the decrease in enzyme function.