Towards a novel small animal proton irradiation platform: the SIRMIO project

Background: Precision small animal radiotherapy research is a young emerging field aiming to provide new experimental insights into tumor and normal tissue models in different microenvironments, to unravel complex mechanisms of radiation damage in target and non-target tissues and assess efficacy of novel therapeutic strategies. For photon therapy, modern small animal radiotherapy research platforms have been developed over the last years and are meanwhile commercially available. Conversely, for proton therapy, which holds potential for an even superior outcome than photon therapy, no commercial system exists yet. Material and methods: The project SIRMIO (Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology) aims at realizing and demonstrating an innovative portable prototype system for precision image-guided small animal proton irradiation, suitable for installation at existing clinical treatment facilities. The proposed design combines precise dose application with in-situ multi-modal anatomical image guidance and in-vivo verification of the actual treatment delivery. Results and conclusions: This manuscript describes the status of the different components under development, featuring a dedicated beamline for degradation and focusing of clinical proton beams, along with novel detector systems for in-situ imaging and range verification. The foreseen workflow includes pre-treatment proton transmission imaging, complemented by ultrasonic tumor localization, for treatment planning and position verification, followed by image-guided delivery with on-site range verification by means of ionoacoustics (for pulsed beams) and positron-emission-tomography (PET, for continuous beams). The proposed compact and cost-effective system promises to open a new era in small animal proton therapy research, contributing to the basic understanding of in-vivo radiation action to identify areas of potential breakthroughs for future translation into innovative clinical strategies

An Advanced Simulation and Reconstruction Framework for a Novel In-Beam PET Scanner for Pre-Clinical Proton Irradiation

Within the project “Small animal proton Irradiator for Research in Molecular Image-guided radiation-Oncology” (SIRMIO) we have designed an in-beam PET scanner for preclinical application. The system is based on a novel spherical geometry, and in order to fully exploit its potential we are developing an integrated computational framework for simulation, image reconstruction and range verification. The software comprises a full Monte Carlo engine to simulate the proton treatment with related detector response, and an image reconstruction tool for simulated and experimental data. The platform is designed to integrate robust analytical reconstruction algorithms and new statistical approaches based on deep learning. The core of the framework is based on MEGAlib (The Medium Energy Gamma-ray Astronomy software library). The physical simulation is based on GEANT4. The machine learning method for the event classification is implemented with the ROOT based Toolkit for Multivariate Data Analysis (TMVA). The first prototype of the SIRMIO irradiation platform foresees a fixed beam, thus requiring the movement of the mouse for scanned beam delivery. Hence, we have extended the MEGAlib image reconstruction algorithm based on maximum-likelihood expectation-maximization (ML-EM) to correct for geometrical efficiency and attenuation taking into account the mouse motion. The goal is to be able to discriminate proton range shifts of ~ 0.5 mm. Moreover, we are augmenting the image reconstruction framework with a new approach based on machine learning, which aims at using all photon events collected during irradiation (dominated by prompt gamma) to retrieve on-the-fly the range of the beam, to complement the PET information

Depth dose measurements in water for 11C and 10C beams with therapy relevant energies

Owing to the favorable depth-dose distribution and the radiobiological properties of heavy ion radiation, ion beam therapy shows an improved success/toxicity ratio compared to conventional radiotherapy. The sharp dose gradients and very high doses in the Bragg peak region, which represent the larger physical advantage of ion beam therapy, make it also extremely sensitive to range uncertainties. The use of beta(+) - radioactive ion beams would be ideal for simultaneous treatment and accurate online range monitoring through PET imaging. Since all the unfragmented primary ions are potentially contributing to the PET signal, these beams offer an improved image quality while preserving the physical and radiobiological advantages of the stable counterparts. The challenging production of radioactive ion beams and the difficulties in reaching high intensities, have discouraged their clinical application. In this context, the project Biomedical Applications of Radioactive ion Beams (BARB) started at GSI (Helmholtzzentrum fur Schwerionenforschung GmbH) with the main goal to assess the technical feasibility and investigate possible advantages of radioactive ion beams on the pre-clinical level. During the first experimental campaign C-11 and C-10 beams were produced and isotopically separated with the FRagment Separator (FRS) at GSI. The beta(+)-radioactive ion beams were produced with a beam purity of 99% for all the beam investigated (except one case where it was 94%) and intensities potentially sufficient to treat a small animal tumors within few minutes of irradiation time, similar to 10(6) particle per spill for the C-10 and similar to 10(7) particle per spill for the C-11 beam, respectively. The impact of different ion optical parameters on the depth dose distribution was studied with a precision water column system. In this work, the measured depth dose distributions are presented together with results from Monte Carlo simulations using the FLUKA software

Radioactive Beams for Image-Guided Particle Therapy : The BARB Experiment at GSI

Several techniques are under development for image-guidance in particle therapy. Positron (β+) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by β+-emitters generated via projectile fragmentation. A much higher intensity for the PET signal can be obtained using β+-radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy.peerReviewe