The role of magnetic resonance for assessing radiation-induced lung damage.

PURPOSE: To investigate the potential role of Magnetic Resonance for assessing radiation-Induced lung damage. METHODS AND MATERIALS: T1 and T2 relaxation times were measured for lungs excised from Sprague-Dawley rats at various times following thoracic irradiation. RESULTS: Although on average a 10% increase was observed in the T2 relaxation times between 30 and 80 days after irradiation, this is too small to affect image contrast. CONCLUSIONS: The results indicate that relaxation measurements are unlikely to yield new information to characterize changes in lung tissue caused by radiation.

Radiation-induced lung damage in rats: the influence of fraction spacing on effect per fraction.

PURPOSE: When the linear-quadratic model is used to predict fractionated treatments which are isoeffective, it is usually assumed that each (equal size) treatment fraction has an equal effect, independent of the time at which it was delivered during a course of treatment. Previous work by our group has indicated that this assumption may not be valid in the context of radiation-induced lung damage in rats. Consequently we tested directly the validity of the assumption that each fraction has an equal effect, independent of the time it is delivered. METHODS AND MATERIALS: An experiment was completed in which fractionated irradiation was given to whole thoraces of Sprague-Dawley rats. All treatment schedules consisted of eleven equal dose fractions in 36 days given as a split course, with some groups receiving the bulk of the doses early in the treatment schedule, before a 27-day gap, and others receiving most of the dose toward the end of the treatment schedule, after the time gap. To monitor the incidence of radiation-induced damage, breathing rate and lethality assays were used. RESULTS: The maximum differences in the LD50s and breathing rate ED50s for the different fractionation schedules were 4.0% and 7.7% respectively. The lethality data and breathing rate data were consistent with results expected from modelling using the linear-quadratic model with the inclusion of an overall time factor, but not the generalized linear-quadratic model which accounted for fraction spacing. CONCLUSION: For conventional daily fractionation, and within the range of experimental uncertainties, the results indicate that the effect of a treatment fraction does not depend on the time at which it is given (its position) in the treatment. The results indicate no need to extend isoeffect formulae to consider the effect of each fraction separately for radiation-induced lung damage.

Ultrasonic measurements of breathing rate in rats and computer assisted analysis.

PURPOSE: An ultrasound breathing rate measurement technique and a computer analysis algorithm have been developed to reduce the amount of time needed to collect and analyze animal breathing rate data, as well as to improve the testing environment. The system is not airtight, therefore, acclimatization and collection time is not limited, and the technique makes use of a top loading apparatus to facilitate animal entry. METHODS AND MATERIALS: Breathing rate is measured using two ultrasound transducers housed directly above the rat thorax in the plexiglass jig. The breathing rate signal is stored and evaluated by computer. The ultrasound technique was tested using a loud speaker driven by a signal generator, over a range of 30 to 450 cycles/min. In addition, the ultrasonic breathing rate method was used to record the breathing rate response of Sprague Dawley rats, treated with graded single doses of radiation, over a period of 170 days. RESULTS: For the loud speaker tests, the measured frequency agreed with that of the input signal with a maximum deviation of 1%. For the animal irradiations, all breathing rate data were analyzed by both user and computer selection of regular breathing. The techniques gave the same results at the 95% confidence limit. Using the computer program to assess the traces, 240 breathing rates can be determined per hour, from previously measured data. CONCLUSION: A new technique for measuring breathing rate has been developed and enhances both the collection and analysis of data.

Evaluation of isoeffect formulae for predicting radiation-induced lung damage.

An experiment has been performed in which fractionated irradiation was given to the whole thorax of Sprague-Dawley rats with schedules chosen so that doses per fraction and overall treatment time were changed independently. Damage was monitored by lethality. The data have been analyzed to yield dose per fraction and time parameters using multiple non-linear regression analysis. The results show that a linear-quadratic cell survival formula, extended to include an exponential time component to account for proliferation or slow repair during the treatment, can predict isoeffective doses to within 7% accuracy over a wide range of times (3.5-49 days) and doses per fraction (1.8-10.2 Gy). Other isoeffect formulae based on the linear-quadratic and empirical power law functions were also evaluated. A linear-quadratic formula with a time dependent alpha parameter fitted the data particularly well. This result suggests an alternative underlying mechanism and requires further investigation.