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As magnetic resonance-guided radiotherapy (MRgRT) is becoming increasingly important in clinical applications, the development of new quality assurance (QA) methods is needed. One important aspect is the alignment of the radiation and imaging isocenter. MR-visible polymer gels offer a way to perform such measurements online and additionally may allow for 3-dimensional (3D) evaluation. We present a star shot measurement irradiated and scanned with a 0.35 T MR-LINAC device evaluating the polyacrylamide gelatin (PAGAT) gel dosimeter immediately and 48 h after irradiation. The gel was additionally scanned at a 3 T MR device 5 h and 52 h after irradiation. The evaluation revealed an isocircle radius of 0.5 mm for both imaging devices and all image resolutions and time points after irradiation. The distance between radiation and imaging isocenter varied between 0.25 mm and 1.30 mm depending on the applied image resolution. This demonstrates that evaluation of a star shot measurement in a 0.35 T MR-LINAC is feasible, even immediately after irradiation.

The implementation of new image-guided radiotherapy (IGRT) treatment techniques requires the development of new quality assurance (QA) methods including geometric and dosimetric validation of the applied dose in 3D. Polymer gels (PG) provide a promising tool to perform such tests. However, to be used in a large variety of clinical applications, the PG must be flexibly applicable. In this work, we present a variety of phantoms used in clinical routine to perform both hardware and workflow tests in IGRT. This includes the validation of isocenter accuracy in magnetic resonance (MR)-guided RT (MRgRT) and end-to-end tests of online adaptive treatment techniques for inter- and intra-fraction motion management in IGRT. The phantoms are equipped with one or more PG containers of different materials including 3D printed containers to allow for 3D dosimetry in arbitrarily shaped structures. The proposed measurement techniques and phantoms provide a flexible application and show a clear benefit of PG for 3D dosimetry in combination with end-to-end tests in many clinical QA applications.

This study aims to evaluate an in-house developed 4D dose calculation algorithm that uses Calypso motion tracking data and to compare the results against 3D polymer gel dosimetry measurements. For this, a cylindrical water phantom was constructed that allows to insert (i) the polymer gel, (ii) a PinPoint ® ionization chamber and (iii) Calypso beacons™ for motion tracking. A treatment plan covering a gel flask in the center of the static phantom plus a 1 mm margin homogeneously with dose was generated. During irradiation, however, the phantom was moved periodically by means of a robot with a peak-to-peak amplitude of 2.5 cm. The results of the 4D dose calculations show good agreement with the gel-dosimetric measurements in most of the volume. Remaining small deviations have to be evaluated in further experiments. The developed experimental setup allows for 3D-dosimetric validation of 4D dose calculations algorithms prior to application in patients.

A dynamic ex-vivo porcine lung phantom combined with polymer gel dosimetry is tested as a new tool to validate modern adaptive radiotherapy techniques (e.g. gating or tracking). The gel was inserted into the lung via a latex balloon to simulate a tumor. After irradiation, the location of the dose maximum was verified, however, the dose was higher than planned and a high background signal was seen. Potential reasons for this finding are the nonstandard conditions of gel handling. These conditions were systematically studied. Besides temperature, the material of the balloon seems to be of special importance. The results identify open issues that have to be addressed in future studies.

Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D) = 1/[1 + (D50/D)k] to the experimental data, 2 intuitive quantities are obtained: the tolerance dose D50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D50 and k as well as their standard errors. The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. Explicit formulas are presented, which allow to calculate the parameters D50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. Statistical artifacts in experiments containing small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level.

A new treatment planning program was developed for the heavy-ion therapy facility at GSI. In addition, a concise quality standard for treatment planning has been set up. It covers acceptance and constancy checks of all critical aspects in treatment planning. Dose verification measurements done during the commissioning phase show an overall good agreement with the treatment planning calculations.

The sensitivity of the rat spinal cord to single and split doses of radiation and the resulting relative biological effectiveness (RBE) were determined for carbon-ion irradiations (12C) in the plateau and Bragg-peak regions. The cranial part of the cervical and thoracic spinal cords of 180 rats were irradiated with one or two fractions of 12C ions or photons, respectively. Dose-response curves for the end point symptomatic myelopathy were established, and the resulting values for the ED50 (dose for 50% complication probability) were used to determine the RBEs. A median latency for myelopathy of 167 days (range, 121-288 days) was found. The ED50 values were 17.1 +/- 0.8 Gy, 24.9 +/- 0.7 Gy (one and two fractions, 12C plateau) and 13.9 +/- 0.8, 15.8 +/- 0.7 Gy (one and two fractions, 12C Bragg peak), respectively. For photons we obtained ED50 values of 24.5 +/- 0.8 Gy for single doses and 34.2 +/- 0.7 Gy when two fractions were applied. The corresponding RBEs were 1.43 +/- 0.08, 1.37 +/- 0.12 (one and two fractions, 12C plateau) and 1.76 +/- 0.05, 2.16 +/- 0.11 (one and two fractions, 12C Bragg peak), respectively. Hematoxylin and eosin staining revealed necrosis of the white matter in the spinal cord in all symptomatic animals. In summary, from one- and two-fraction photon, 12C plateau and Bragg-peak irradiation of the rat spinal cord, we have established RBEs as well as the individual ED50's. From the latter there is a clear indication of repair processes for fractionated photons and 12C plateau ions which are significantly reduced by using Bragg-peak ions. Additional studies are being carried with 6 and 18 fractions to further refine and define the RBE and ED50 values and estimate the alpha/beta ratios.The sensitivity of the rat spinal cord to single and split doses of radiation and the resulting relative biological effectiveness (RBE) were determined for carbon-ion irradiations (12C) in the plateau and Bragg-peak regions. The cranial part of the cervical and thoracic spinal cords of 180 rats were irradiated with one or two fractions of 12C ions or photons, respectively. Dose-response curves for the end point symptomatic myelopathy were established, and the resulting values for the ED50 (dose for 50% complication probability) were used to determine the RBEs. A median latency for myelopathy of 167 days (range, 121-288 days) was found. The ED50 values were 17.1 +/- 0.8 Gy, 24.9 +/- 0.7 Gy (one and two fractions, 12C plateau) and 13.9 +/- 0.8, 15.8 +/- 0.7 Gy (one and two fractions, 12C Bragg peak), respectively. For photons we obtained ED50 values of 24.5 +/- 0.8 Gy for single doses and 34.2 +/- 0.7 Gy when two fractions were applied. The corresponding RBEs were 1.43 +/- 0.08, 1.37 +/- 0.12 (one and two fractions, 12C plateau) and 1.76 +/- 0.05, 2.16 +/- 0.11 (one and two fractions, 12C Bragg peak), respectively. Hematoxylin and eosin staining revealed necrosis of the white matter in the spinal cord in all symptomatic animals. In summary, from one- and two-fraction photon, 12C plateau and Bragg-peak irradiation of the rat spinal cord, we have established RBEs as well as the individual ED50's. From the latter there is a clear indication of repair processes for fractionated photons and 12C plateau ions which are significantly reduced by using Bragg-peak ions. Additional studies are being carried with 6 and 18 fractions to further refine and define the RBE and ED50 values and estimate the alpha/beta ratios.

The sensitivity of the rat spinal cord to single and split doses of radiation and the resulting relative biological effectiveness (RBE) were determined for carbon-ion irradiations $({}^{12}{\\rm C})$ in the plateau and Bragg-peak regions. The cranial part of the cervical and thoracic spinal cords of 180 rats were irradiated with one or two fractions of 12 C ions or photons, respectively. Dose-response curves for the end point symptomatic myelopathy were established, and the resulting values for the ED50 (dose for 50% complication probability) were used to determine the RBEs. A median latency for myelopathy of 167 days (range, 121-288 days) was found. The ED50 values were 17.1 ± 0.8 Gy, 24.9 ± 0.7 Gy (one and two fractions, 12 C plateau) and 13.9 ± 0.8, 15.8 ± 0.7 Gy (one and two fractions, 12 C Bragg peak), respectively. For photons we obtained ED50 values of 24.5 ± 0.8 Gy for single doses and 34.2 ± 0.7 Gy when two fractions were applied. The corresponding RBEs were 1.43 ± 0.08, 1.37 ± 0.12 (one and two fractions, 12 C plateau) and 1.76 ± 0.05, 2.16 ± 0.11 (one and two fractions, 12 C Bragg peak), respectively. Hematoxylin and eosin staining revealed necrosis of the white matter in the spinal cord in all symptomatic animals. In summary, from one- and two-fraction photon, 12 C plateau and Bragg-peak irradiation of the rat spinal cord, we have established RBEs as well as the individual ED50's. From the latter there is a clear indication of repair processes for fractionated photons and 12 C plateau ions which are significantly reduced by using Bragg-peak ions. Additional studies are being carried with 6 and 18 fractions to further refine and define the RBE and ED50 values and estimate the α/β ratios.

This study investigated late effects in the brain after irradiation with carbon ions using a rat model. Thirty-six animals were irradiated stereotactically at the right frontal lobe using an extended Bragg peak with maximum doses between 15.2 and 29.2 Gy. Dose-response curves for late changes in the normal brain were measured using T1- and T2-weighted magnetic resonance imaging (MRI). Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were progressive in time up to 17 months and remained stationary after that time. At 20 months the tolerance doses at the 50% effect probability level were 20.3 plus or minus 2.0 Gy and 22.6 plus or minus 2.0 Gy for changes in T1- and T2-weighted MRI, respectively. The relative biological effectiveness (RBE) was calculated on the basis of a previous animal study with photons. Using tolerance doses at the 50% effect probability level, RBE values of 1.95 plus or minus 0.20 and 1.88 plus or minus 0.18 were obtained for T1- and T2-weighted MRI. A comparison with data in the literature for the spinal cord yielded good agreement, indicating that the RBE values for single-dose irradiations of the brain and the spinal cord are the same within the experimental uncertainty.

Late reaction of normal tissue is still a limiting factor in radiotherapy and radiosurgery of patients with brain tumors. Few quantitative data in terms of dose-response curves are available. In the present study, 99 animals were irradiated stereotactically at the right frontal lobe using a linear accelerator and single doses between 26 and 50 Gy. The diameter of the spherical dose distribution was 4.7 mm (80% isodose). Dose-response curves for late changes in the normal brain at 20 months were measured using T1- and T2-weighted magnetic resonance imaging (MRI). The dependence of the dose-response curves on the follow-up time and the definition of the biological end point were determined. Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were found to be dependent on dose and progressive in time. At 20 months, the tolerance doses at a 50% effect probability level were 39.6 c 1.0 Gy and 42.4 c 1.4 Gy for changes in T1- and T2-weighted images, respectively. These dose-response curves can be used for further quantitative investigations on the influence of various treatment parameters, such as the application of charged particles, radiopharmaceuticals or the variation of tissue oxygenation.