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Radioactive ion beams (RIB) are a key focus of current research in nuclear physics. Already long ago it was proposed that they could have applications in cancer therapy. In fact, while charged particle therapy is potentially the most effective radiotherapy technique available, it is highly susceptible to uncertainties in the beam range. RIB are well-suited for image-guided particle therapy, as isotopes that undergo \b{eta}+-decay can be precisely visualized using positron emission tomography (PET), enabling accurate real-time monitoring of the beam range. We successfully treated a mouse osteosarcoma using a radioactive 11C-ion beam. The tumor was located in the neck, in close proximity to the spinal cord, increasing the risk of radiation-induced myelopathy from even slight variations in the beam range caused by anatomical changes or incorrect calibration of the planning CT. We managed to completely control the tumor with the highest dose while minimizing toxicity. Low-grade neurological side effects were correlated to the positron activity measured in the spine. The biological washout of the activity from the tumor volume was dependent on the dose, indicating a potential component of vascular damage at high doses. This experiment marks the first instance of tumor treatment using RIB and paves the way for future clinical applications., Comment: 56 pages, 13 figures, supplements. Video supplements available on request

We present a multi-scale formalism that accounts for the formation of nano-scale bubbles/cavities owing to a burst of water molecules after the passage of high energy charged particles that leads to the formation of hot non-ionizing excitations or thermal spikes (TS). We demonstrate the coexistence of a rapidly growing condensed state of water and a hot spot that forms a stable state of diluted water at high temperatures and pressures, possibly at a supercritical phase. Depending on the temperature of TS, the thin shell of a highly dense state of water grows by three to five times the speed of sound in water, forming a thin layer of shock wave (SW) buffer, wrapping around the nano-scale cylindrical symmetric cavity. The stability of the cavity, as a result of the incompressibility of water at ambient conditions and the surface tension, allows the transition of supersonic SW to a subsonic contact discontinuity and dissipation to thermo-acoustic sound waves. We further study the mergers of nanobubbles that lead to fountain-like or jet-flow structures at the collision interface. We introduce a time delay in the nucleation of nano-bubbles, a novel mechanism, responsible for the growth and stability of much larger or even micro-bubbles, possibly relevant to FLASH ultra-high dose rate (UHDR). The current study is potentially significant at FLASH-UHDRs. Our analysis predicts the black-body radiation from the transient supercritical state of water localized in nano-cavities wrapping around the track of charged particles can be manifested in the (indirect) water luminescence spectrum.

Purpose: To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy. Materials and Methods: Phantoms of polyethylene, gelatin or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent $^{11}$C, $^{10}$C and $^{15}$O radionuclides contributions in each voxel were determined from the extracted time activity curves. Experiments were simulated in Geant4 Monte Carlo versions 10-11.1, with three different fragmentation models: binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 combinations. Total/parent isotope positron annihilation yields were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Depth of maximum/distal 50\% peak position yield were also compared. Results: Performance varied considerably across versions and models, with no one best predicting all positron-emitting fragments. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50\%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions. Conclusions: Best spatial prediction of annihilation yield and positron-emitting fragment production during carbon and oxygen ion therapy was found to be 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research., Comment: This manuscript has been submitted to IOP's Journal of Physics in Medicine and Biology, on the 5th of February 2024

Radiotherapy with heavy ions, in particular, 12C beams, is one of the most advanced forms of cancer treatment. Sharp dose gradients and high biological effectiveness in the target region make them an ideal tool to treat deep-seated and radioresistant tumors, however, at the same time, sensitive to small errors in the range prediction. Safety margins are added to the tumor volume to mitigate these uncertainties and ensure its uniform coverage, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the benefits of a sharp Bragg peak, a large effort is put into establishing precise range verification methods for the so-called image-guided radiotherapy. Despite positron emission tomography being widely in use for this purpose in 12C ion therapy, the low count rates, biological washout, and broad shape of the activity distribution still limit its precision to a few millimeters. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C beams treatments, on sparing critical organs in the tumor proximity. We demonstrate that (i) annihilation maps for 11C ions can in principle reflect even millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C beams are significantly improved in terms of meeting the constraints for the organs at risk compared to 12C plans, and (iii) less severe toxicities for serial and parallel critical organs can be expected following 11C treatment with reduced range uncertainties, compared to 12C treatments.

The maximum energy loss (Bragg peak) located near the end of range is a characteristic feature of ion stopping in matter, which generates an acoustic pulse, if ions are deposited into a medium in adequately short bunches. This so-called ionoacoustic effect has been studied for decades, mainly for astrophysical applications, and it has recently found renewed interest in proton therapy for precise range measurements in tissue. After detailed preparatory studies with 20 MeV protons at the MLL tandem accelerator, ionoacoustic range measurements were performed in water at the upgraded SIS18 synchrotron of GSI with 238U and 124Xe ion beams of energy about 300 MeV/u, and 12C ions of energy about 200 MeV/u using fast beam extraction to get 1 microsecond pulse lengths. Acoustic signals were recorded in axial geometry by standard piezo-based transducers at a 500 kHz mean frequency and evaluated in both the time and frequency domains. The resulting ranges for the different ions and energies were found to agree with Geant4 simulations as well as previous measurements to better than 1%. Given the high accuracy provided by ionoacoustic range measurements in water and their relative simplicity, we propose this new method for stopping power measurements for heavy ions at GeV energies and above. Our experimental results clearly demonstrate the potential of an ionoacoustic particle monitor especially for very intense heavy ion beams foreseen at future accelerator facilities., Comment: 22 pages, 15 figures, 3 tables, submitted to Nucl Instr Meth A

The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a generalization of the ionoacoustic approach. Featuring compactness, simple operation, indestructibility and high dynamic ranges in energy and intensity, I-BEAT is a promising approach to meet the needs of petawatt-class laser-based ion accelerators. With its capability of completely monitoring a single, focused proton bunch with prompt readout it, is expected to have particular impact for experiments and applications using ultrashort ion bunches in high flux regimes. We demonstrate its functionality using it with two laser-driven ion sources for quantitative determination of the kinetic energy distribution of single, focused proton bunches., Comment: Paper: 17 Pages, 3 figures Supplementary Material 16 pages, 7 figures

With the continued evolution of modern radiation therapy towards high precision delivery of high therapeutic doses to the tumour while optimally sparing surrounding healthy tissue, imaging becomes a crucial component to identify the intended target, properly position it at the treatment site and, in more advanced research applications, visualize the treatment delivery. This contribution reviews the main role of imaging in modern external beam radiation therapy, with special emphasis on emerging ion beam therapy techniques, which aim at exploiting the favourable properties of ion interaction in matter for unprecedented ballistic accuracy in dose delivery, Comment: 8 pages, Presented at the CAS- CERN Accelerator School on Accelerators for Medical Application, V\"osendorf, Austria, 26 May - 5 June, 2015

We report on the optimization of discharge insensitive floating strip Micromegas (MICRO-MEsh GASeous) detectors, fit for use in high-energy muon spectrometers. The suitability of these detectors for particle tracking is shown in high-background environments and at very high particle fluxes up to 60MHz/cm$^2$. Measurement and simulation of the microscopic discharge behavior have demonstrated the excellent discharge tolerance. A floating strip Micromegas with an active area of 48cm$\times$50cm with 1920 copper anode strips exhibits in 120GeV pion beams a spatial resolution of 50$\mu$m at detection efficiencies above 95%. Pulse height, spatial resolution and detection efficiency are homogeneous over the detector. Reconstruction of particle track inclination in a single detector plane is discussed, optimum angular resolutions below $5^\circ$ are observed. Systematic deviations of this $\mu$TPC-method are fully understood. The reconstruction capabilities for minimum ionizing muons are investigated in a 6.4cm$\times$6.4cm floating strip Micromegas under intense background irradiation of the whole active area with 20MeV protons at a rate of 550kHz. The spatial resolution for muons is not distorted by space charge effects. A 6.4cm$\times$6.4cm floating strip Micromegas doublet with low material budget is investigated in highly ionizing proton and carbon ion beams at particle rates between 2MHz and 2GHz. Stable operation up to the highest rates is observed, spatial resolution, detection efficiencies, the multi-hit and high-rate capability are discussed., Comment: Presented at ICHEP 2014, accepted for publication in Nuclear Physics B Proceedings Supplements