Objective.Adaptive radiotherapy (ART) requires robust end-to-end (E2E) testing tools capable of reproducing organ deformation, physiological motion, and multimodal imaging properties. TheToraco-abdominalAnthropomorphic Phantom withMotion forAdaptiveRadiotherapy (TAM-ARa) is a dynamic anthropomorphic phantom developed to support the design, validation, and quality assurance of online ART workflows.Approach.The phantom was constructed with anatomically realistic bone, lung, and abdominal organ models fabricated from tissue equivalent materials. Modular components allowed simulation of interfractional and intrafractional anatomical variations, including ventilator driven respiratory motion, abdominal deformation, and variable gastric filling. CT, CBCT, and 3T MRI scans were acquired to assess imaging performance. Two E2E tests of an online adaptive intensity-modulated radiotherapy (IMRT) workflow for liver tumors were performed on a Varian Ethos (ETHOS, Varian, USA) system. Multiple deformation scenarios were investigated, including a static reference configuration, two abdominal and one thoracic deformation for ionization chamber (IC) dosimetry, and a static plus abdominal deformation scenarios for radiochromic film dosimetry.Main results.The TAM-ARa phantom demonstrated realistic radiological characteristics, with CT Hounsfield units and MRI relaxation times closely matching reportedin vivovalues. The modular architecture allowed reproducible and controlled abdominal deformations, while setup and dosimeter placement were completed within minutes. In E2E tests for adaptive IMRT of liver tumors, excellent agreement was achieved between measured and planned dose distributions after the treatment plan was adapted. IC E2E measurements showed that online adaptation consistently restored accurate dose delivery under deformation, reducing deviations to below 3%. Independent film measurements confirmed sub-millimeter geometric accuracy and full planning target volume coverage after adaptation, demonstrating effective compensation of deformation-induced errors.Significance.The TAM-ARa phantom provides a versatile and reproducible platform for multimodal E2E testing and validation of online ART workflows. Employing its realistic anatomical design, modular structure, and motion capabilities, TAM-ARa was successfully applied for E2E tests to validate a workflow for adaptive IMRT of liver tumors.

BACKGROUND:The pursuit of adaptive radiotherapy using MR imaging for better precision in patient positioning puts stringent demands on the hardware components of the MR scanner. Particularly in particle therapy, the dose distribution and thus the efficacy of the treatment is susceptible to beam attenuation from interfering materials in the irradiation path. This severely limits the usefulness of conventional imaging coils, which contain highly attenuating parts such as capacitors and preamplifiers in an unknown position, and requires development of a dedicated radiofrequency (RF) coil with close consideration of the materials and components used. PURPOSE:In MR-guided radiation therapy in the human torso, imaging coils with a large FOV and homogeneous B1 field distribution are required for reliable tissue classification. In this work, an imaging coil for MR-guided particle therapy was developed with minimal ion attenuation while maintaining flexibility in treatment. METHODS:A birdcage coil consisting of nearly radiation-transparent materials was designed and constructed for a closed-bore 1.5 T MR system. Additionally, the coil was mounted on a rotatable patient capsule for flexible positioning of the patient relative to the beam. The ion attenuation of the RF coil was investigated in theory and via measurements of the Bragg peak position. To characterize the imaging quality of the RF coil, transmit and receive field distributions were simulated and measured inside a homogeneous tissue-simulating phantom for various rotation angles of the patient capsule ranging from 0° to 345° in steps of 15°. Furthermore, simulations with a heterogeneous human voxel model were performed to better estimate the effect of real patient loading, and the RF coil was compared to the internal body coil in terms of SNR for a full rotation of the patient capsule. RESULTS:The RF coil (total water equivalent thickness (WET) ≈ 420 µm, WET of conductor ≈ 210 µm) can be considered to be radiation-transparent, and a measured transmit power efficiency (B1 +/ P $\sqrt {\mathrm{P}} $ ) between 0.17 µT/ W $\sqrt {\mathrm{W}} $ and 0.26 µT/ W $\sqrt {\mathrm{W}} $ could be achieved in a volume (Δz = 216 mm, complete x and y range) for the 24 investigated rotation angles of the patient capsule. Furthermore, homogeneous transmit and receive field distributions were measured and simulated in the transverse, coronal and sagittal planes in a homogeneous phantom and a human voxel model. In addition, the SNR of the radiation-transparent RF coil varied between 103 and 150, in the volume (Δz = 216 mm) of a homogeneous phantom and surpasses the SNR of the internal body coil for all rotation angles of the patient capsule. CONCLUSIONS:A radiation-transparent RF coil was developed and built that enables flexible patient to beam positioning via full rotation capability of the RF coil and patient relative to the beam, with results providing promising potential for adaptive MR-guided particle therapy.

Background Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study. Method A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated. Results Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants. Conclusion Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.

Background: In-vivo monitoring methods of carbon ion radiotherapy (CIRT) includes explorations of nuclear reaction products generated by carbon-ion beams interacting with patient tissues. Our research group focuses on in-vivo monitoring of CIRT using silicon pixel detectors. Currently, we are conducting a prospective clinical trial as part of the In-Vivo Monitoring project (InViMo) at the Heidelberg Ion Beam Therapy Center (HIT) in Germany. We are using an innovative, in-house developed, non-contact fragment tracking system with seven mini-trackers based on the Timepix3 technology developed at CERN. Purpose: This article focuses on the implementation of the mini-tracker in Monte Carlo (MC) based on FLUKA simulations to monitor secondary charged nuclear fragments in CIRT. The main objective is to systematically evaluate the simulation accuracy for the InViMo project. Methods: The implementation involved integrating the mini-tracker geometry and the scoring mechanism into the FLUKA MC simulation, utilizing the finely tuned HIT beam line. The systematic investigation included varying mini-tracker angles (from 15 degrees to 45 degrees in 5 degrees steps) during the irradiation of a head-sized phantom with therapeutic carbon-ion pencil beams. To evaluate our implemented FLUKA framework, a comparison was made between the experimental data and data obtained from MC simulations. To ensure the fidelity of our comparison, experiments were performed at the HIT using the parameters and setup established in the simulations. Results: Our research demonstrates high accuracy in reproducing characteristic behaviors and dependencies of the monitoring method in terms of fragment distributions in the mini-tracker, track angles, emission profiles, and fragment numbers. Discrepancies in the number of detected fragments between the experimental data and the data obtained from MC simulations are less than 4% for the angles of interest in the InViMo detection system. Conclusions: Our study confirms the potential of our simulation framework to investigate the performance of monitoring inter-fractional anatomical changes in patients undergoing CIRT using secondary nuclear charged fragments escaping from the irradiated patient.

Objective.The highly conformal carbon-ion radiotherapy is associated with an increased sensitivity of the dose distributions to internal changes in the patient during the treatment course. Hence, monitoring methodologies capable of detecting such changes are of vital importance. We established experimental setup conditions to address the sensitivity of a monitoring approach based on secondary-fragment tracking for detecting clinically motivated air cavity dimensions in a homogeneous head-sized PMMA phantom in 40 mm depth.Approach.The air cavities were positioned within the entrance channel of a treatment field of 50 mm diameter at three lateral positions. The measured secondary-fragment emission profiles were compared to a reference measurement without cavities. The experiments were conducted at the Heidelberg Ion-Beam Therapy Center in Germany at typical doses and dose rates.Main results.Significances above a detectability threshold of 2σfor the larger cavities (20 mm diameter and 4 mm thickness, and 20 mm diameter and 2 mm thickness) across the entire treatment field. The smallest cavity of 10 mm diameter and 2 mm thickness, which is on the lower limit of clinical interest, could not be detected at any position. We also demonstrated that it is feasible to reconstruct the lateral position of the cavity on average within 2.8 mm, once the cavity is detected. This is sufficient for the clinicians to estimate medical effects of such a cavity and to decide about the need for a control imaging CT.Significance.This investigation defines well-controlled reference conditions for the evaluation of the performance of any kind of treatment monitoring method and its capability to detect internal changes within head-sized objects. Four air cavities with volumes between 0.31 cm3and 1.26 cm3were narrowed down around the detectability threshold of this secondary-fragment-based monitoring method.

The precision of carbon-ion radiotherapy in delivering radiation dose to the tumor while sparing adjacent healthy tissue surpasses that of conventional X-ray radiotherapy, offering a significant advantage in treatment. However, this comes with an increased sensitivity of the treatment quality to deformations and displacements of tissue, which can arise from morphological changes inside the patient or inaccuracies in patient positioning. To address this issue, we have been developing a non-invasive in-vivo treatment monitoring method based on the tracking of charged nuclear fragments produced by interactions of the carbon ions with nuclei of the patient’s tissue. The measured tracks allow the reconstruction of fragment origins, whose distributions can be compared between different treatment fractions. In this comparison, interfractional changes of the patient’s morphology or positioning may be uncovered. A unique detection system consisting of 28 Timepix3 silicon pixel detectors for usage during patient treatments at the Heidelberg Ion Beam Therapy Center (HIT) was developed and built. This detection system is being used in an ongoing prospective clinical trial named InViMo (In-Vivo Monitoring) with the purpose of detecting internal changes in the skull base region. This work presents the latest results from monitoring measurements during patient treatments. Changes in the distribution of charged nuclear fragments, which could arise from deformations and displacements of the patient’s tissue, were observed for several patients. These results pave the way towards increasing the benefits of carbon-ion radiotherapy for many patients through in-vivo monitoring, as reduced uncertainties could facilitate dose escalation and the reduction of safety margins.

Ion-beam radiotherapy is an advanced cancer treatment modality offering steep dose gradients and a high biological effectiveness. These gradients make the therapy vulnerable to patient-setup and anatomical changes between treatment fractions, which may go unnoticed. Charged fragments from nuclear interactions of the ion beam with the patient tissue may carry information about the treatment quality. Currently, the fragments escape the patient undetected. Inter-fractional in-vivo treatment monitoring based on these charged nuclear fragments could make ion-beam therapy safer and more efficient. We developed an ion-beam monitoring system based on 28 hybrid silicon pixel detectors (Timepix3) to measure the distribution of fragment origins in three dimensions. The system design choices as well as the ion-beam monitoring performance measurements are presented in this manuscript. A spatial resolution of 4 mm along the beam axis was achieved for the measurement of individual fragment origins. Beam-range shifts of 1.5 mm were identified in a clinically realistic treatment scenario with an anthropomorphic head phantom. The monitoring system is currently being used in a prospective clinical trial at the Heidelberg Ion Beam Therapy Centre for head-and-neck as well as central nervous system cancer patients.

An RF body coil compatible with particle therapy was built for a clinical MR scanner at 1.5T with a rotatable patient capsule. The attenuation of 1 H + and 12 C 6+ ions due to inelastic scattering was calculated for different materials to estimate the detrimental effects of the RF coil on the particle beam. The imaging capabilities could be demonstrated with phantom measurements at different flip angles, and corresponding transmit and receive characteristics were analyzed and compared to electromagnetic field simulations for both a horizontal and a tilted position of a phantom.

BACKGROUND:Interest in spatial fractionation radiotherapy has exponentially increased over the last decade as a significant reduction of healthy tissue toxicity was observed by mini-beam irradiation. Published studies, however, mostly use rigid mini-beam collimators dedicated to their exact experimental arrangement such that changing the setup or testing new mini-beam collimator configurations becomes challenging and expensive.PURPOSE:In this work, a versatile, low-cost mini-beam collimator was designed and manufactured for pre-clinical applications with X-ray beams. The mini-beam collimator enables variability of the full width at half maximum (FWHM), the center-to-center distance (ctc), the peak-to-valley dose ratio (PVDR), and the source-to-collimator distance (SCD).METHODS:The mini-beam collimator is an in-house development, which was constructed of 10 ×  40 mm2 tungsten or brass plates. These metal plates were combined with 3D-printed plastic plates that can be stacked together in the desired order. A standard X-ray source was used for the dosimetric characterization of four different configurations of the collimator, including a combination of plastic plates of 0.5, 1, or 2 mm width, assembled with 1 or 2 mm thick metal plates. Irradiations were done at three different SCDs for characterizing the performance of the collimator. For the SCDs closer to the radiation source, the plastic plates were 3D-printed with a dedicated angle to compensate for the X-ray beam divergence, making it possible to study ultra-high dose rates of around 40 Gy/s. All dosimetric quantifications were performed using EBT-XD films. Additionally, in vitro studies with H460 cells were carried out.RESULTS:Characteristic mini-beam dose distributions were obtained with the developed collimator using a conventional X-ray source. With the exchangeable 3D-printed plates, FWHM and ctc from 0.52 to 2.11 mm, and from 1.77 to 4.61 mm were achieved, with uncertainties ranging from 0.01% to 8.98%, respectively. The FWHM and ctc obtained with the EBT-XD films are in agreement with the design of each mini-beam collimator configuration. For dose rates in the order of several Gy/min, the highest PVDR of 10.09 ± 1.08 was achieved with a collimator configuration of 0.5 mm thick plastic plates and 2 mm thick metal plates. Exchanging the tungsten plates with the lower-density metal brass reduced the PVDR by approximately 50%. Also, increasing the dose rate to ultra-high dose rates was feasible with the mini-beam collimator, where a PVDR of 24.26 ± 2.10 was achieved. Finally, it was possible to deliver and quantify mini-beam dose distribution patterns in vitro.CONCLUSIONS:With the developed collimator, we achieved various mini-beam dose distributions that can be adjusted according to the needs of the user in regards to FWHM, ctc, PVDR and SCD, while accounting for beam divergence. Therefore, the designed mini-beam collimator may enable low-cost and versatile pre-clinical research on mini-beam irradiation.