Initial clinical evaluation of PET-based ion beam therapy monitoring under consideration of organ motion.

PURPOSE: Intrafractional organ motion imposes considerable challenges to scanned ion beam therapy and demands for a thorough verification of the applied treatment. At the Heidelberg Ion-Beam Therapy Center (HIT), the scanned ion beam delivery is verified by means of postirradiation positron-emission-tomography (PET) imaging. This work presents a first clinical evaluation of PET-based treatment monitoring in ion beam therapy under consideration of target motion. METHODS: Three patients with mobile liver lesions underwent scanned carbon ion irradiation at HIT and postirradiation PET/CT (x-ray-computed-tomography) imaging with a commercial scanner. Respiratory motion was recorded during irradiation and subsequent image acquisition. This enabled a time-resolved (4D) calculation of the expected irradiation-induced activity pattern and, for one patient where an additional 4D CT was acquired at the PET/CT scanner after treatment, a motion-compensated PET image reconstruction. For the other patients, PET data were reconstructed statically. To verify the treatment, calculated prediction and reconstructed measurement were compared with a focus on the ion beam range. RESULTS: Results in the current three patients suggest that for motion amplitudes in the order of 2 mm there is no benefit from incorporating respiratory motion information into PET-based treatment monitoring. For a target motion in the order of 10 mm, motion-related effects become more severe and a time-resolved modeling of the expected activity distribution can lead to an improved data interpretation if a sufficient number of true coincidences is detected. Benefits from motion-compensated PET image reconstruction could not be shown conclusively at the current stage. CONCLUSIONS: The feasibility of clinical PET-based treatment verification under consideration of organ motion has been shown for the first time. Improvements in noise-robust 4D PET image reconstruction are deemed necessary to enhance the clinical potential.

4D offline PET-based treatment verification in scanned ion beam therapy: a phantom study.

At the Heidelberg Ion-Beam Therapy Center, patient irradiation with scanned proton and carbon ion beams is verified by offline positron emission tomography (PET) imaging: the ß+-activity measured within the patient is compared to a prediction calculated on the basis of the treatment planning data in order to identify potential delivery errors. Currently, this monitoring technique is limited to the treatment of static target structures. However, intra-fractional organ motion imposes considerable additional challenges to scanned ion beam radiotherapy. In this work, the feasibility and potential of time-resolved (4D) offline PET-based treatment verification with a commercial full-ring PET/CT (x-ray computed tomography) device are investigated for the first time, based on an experimental campaign with moving phantoms. Motion was monitored during the gated beam delivery as well as the subsequent PET acquisition and was taken into account in the corresponding 4D Monte-Carlo simulations and data evaluation. Under the given experimental conditions, millimeter agreement between the prediction and measurement was found. Dosimetric consequences due to the phantom motion could be reliably identified. The agreement between PET measurement and prediction in the presence of motion was found to be similar as in static reference measurements, thus demonstrating the potential of 4D PET-based treatment verification for future clinical applications.

Preclinical investigations towards the first spacer gel application in prostate cancer treatment during particle therapy at HIT.

BACKGROUND: The application of spacer gel represents a promising approach to reliably spare the rectal frontal wall during particle therapy (IJROBP 76:1251-1258, 2010). In order to qualify the spacer gel for the clinical use in particle therapy, a variety of measurements were performed in order to ensure the biological compatibility of the gel, its physical stability during and after the irradiation, and a proper definition of the gel in terms of the Hounsfield Unit (HU) values for the treatment planning system. The potential for the use of the spacer gel for particle therapy monitoring with off-line Positron Emission Tomography (PET) was also investigated. RESULTS: The spacer gel implanted to the prostate patient in direct neighbourhood to the clinical target volume does not interfere with the particle therapy treatment planning procedure applied at Heidelberg Ion Beam Therapy Centre (HIT). The performed measurements show that Bragg-peak position of the particles can be properly predicted on the basis of computed tomography imaging with the treatment planning system used at HIT (measured water equivalent path length of 1.011 ±0.011 (2σ), measured Hounsfield Unit of 28.9 ±6.1 (2σ)). The spacer gel samples remain physically unchanged after irradiation with a dose exceeding the therapeutic dose level. The independently measured Bragg-Peak position does not change within the time interval of 10 weeks. CONCLUSIONS: As a result of the presented experiments, the first clinical application of spacer gel implant during prostate cancer treatment with carbon ions and protons was possible at HIT in 2012. The reported pre-clinical investigations demonstrate that use of spacer gel is safe in particle therapy in presence of therapy target motion and patient positioning induced particle range variations. The spacer gel injected between prostate and rectum enlarge the distance between both organs, which is expected to clinically significantly decrease the undesirable exposure of the most critical organ at risk, i.e. rectal frontal wall. Further research on the composition of spacer gel material might lead to additional clinical benefits by validation of particle therapy of prostate via post-therapeutic PET-imaging or by patient positioning based on the gel as a radio-opaque marker.

Implementation and initial clinical experience of offline PET/CT-based verification of scanned carbon ion treatment.

BACKGROUND AND PURPOSE: We report on the implementation of offline PET/CT-based treatment verification at the Heidelberg Ion Beam Therapy Centre (HIT) and present first clinical cases for post-activation measurements after scanned carbon ion irradiation. Key ingredient of this in-vivo treatment verification is the comparison of irradiation-induced patient activation measured by a PET scanner with a prediction simulated by means of Monte Carlo techniques. MATERIAL AND METHODS: At HIT, a commercial full-ring PET/CT scanner has been installed in close vicinity to the treatment rooms. After selected irradiation fractions, the patient either walks to the scanner for acquisition of the activation data or is transported using a shuttle system. The expected activity distribution is obtained from the production of ß(+)-active isotopes simulated by the FLUKA code on the basis of the patient-specific treatment plan, post-processed considering the time course of the respective treatment fraction, the estimated biological washout of the induced activity and a simplified model of the imaging process. RESULTS: We present four patients with different indications of head, head/neck, liver and pelvic tumours. A clear correlation between the measured PET signal and the simulated activity pattern is observed for all patients, thus supporting a proper treatment delivery. In the case of a pelvic tumour patient it was possible to detect minor treatment delivery inaccuracies. CONCLUSIONS: The initial clinical experience proves the feasibility of the implemented strategy for offline confirmation of scanned carbon ion irradiation and therefore constitutes a first step towards a comprehensive PET/CT-based treatment verification in the clinical routine at HIT.

Monitoring of patients treated with particle therapy using positron-emission-tomography (PET): the MIRANDA study.

BACKGROUND: The purpose of this clinical study is to investigate the clinical feasibility and effectiveness of offline Positron-Emission-Tomography (PET) quality assurance for promoting the accuracy of proton and carbon ion beam therapy. METHODS/DESIGN: A total of 240 patients will be recruited, evenly sampled among different analysis groups including tumors of the brain, skull base, head and neck region, upper gastrointestinal tract including the liver, lower gastrointestinal tract, prostate and pelvic region. From the comparison of the measured activity with the planned dose and its corresponding simulated activity distribution, conclusions on the delivered treatment will be inferred and, in case of significant deviations, correction strategies will be elaborated. DISCUSSION: The investigated patients are expected to benefit from this study, since in case of detected deviations between planned and actual treatment delivery a proper intervention (e.g., correction) could be performed in a subsequent irradiation fraction. In this way, an overall better treatment could be achieved than without any in-vivo verification. Moreover, site-specific patient-population information on the precision of the ion range at HIT might enable improvement of the CT-range calibration curve as well as safe reduction of the treatment margins to promote enhanced treatment plan conformality and dose escalation for full clinical exploitation of the promises of ion beam therapy. TRIAL REGISTRATION: NCT01528670.

Image formation with a microlens-based optical detector: a three-dimensional mapping approach.

A ray-based approach that models the geometric mapping properties of a flat optical detector based on a microlens array is presented. The investigated optical detector substitutes a single-aperture lens optic for planar and tomographic data acquisition in space-constrained small-animal imaging applications. The formalism implements forward mapping of a three-dimensional object volume onto a two-dimensional sensor surface as well as the backprojection (inverse mapping) of acquired sensor data sets. The object focus distance is the sole free parameter for the inverse mapping. By variation of the object focus distance, arbitrary object surface areas within the computed object images can be focused. The inverse mapping algorithm was applied to an experimentally acquired sensor data set from a three-dimensional phantom. The results are compared with focal point image formation.