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The Centre for Medical Radiation Physics introduced the concept of Silicon On Insulator (SOI) microdosimeters with 3-Dimensional (3D) cylindrical sensitive volumes (SVs) mimicking the dimensions of cells in an array. Several designs of high-definition 3D SVs fabricated using 3D MEMS technology were implemented. 3D SVs were fabricated in different sizes and configurations with diameters between 18 and 30 µm, thicknesses of 2–50 µm and at a pitch of 50 µm in matrices with volumes of 20 × 20 and 50 × 50. SVs were segmented into sub-arrays to reduce capacitance and avoid pile up in high-dose rate pencil beam scanning applications. Detailed TCAD simulations and charge collection studies in individual SVs have been performed. The microdosimetry probe (MicroPlus) is composed of the silicon microdosimeter and low-noise front–end readout electronics housed in a PMMA waterproof sheath that allows measurements of lineal energies as low as 0.4 keV/µm in water or PMMA. Microdosimetric quantities measured with SOI microdosimeters and the MicroPlus probe were used to evaluate the relative biological effectiveness (RBE) of heavy ions and protons delivered by pencil-beam scanning and passive scattering systems in different particle therapy centres. The 3D detectors and MicroPlus probe developed for microdosimetry have the potential to provide confidence in the delivery of RBE optimized particle therapy when introduced into routine clinical practice

A development project for hypo-fractionated multi-ion therapy has been initiated at the National Institute of Radiological Sciences in Japan. In the treatment, helium, carbon, oxygen, and neon ions will be used as primary beams with pencil beam scanning. A ripple filter (RiFi), consisting of a thin plastic or aluminum plate with a fine periodic ridge and groove structure, has been used to broaden the Bragg peak of heavy-ion beams in the beam direction. To sufficiently broaden the Bragg peak of helium-, carbon-, oxygen-, and neon-ion beams with suppressed lateral scattering and surface dose inhomogeneity, in this study, we tested a plate made of a lung substitute material, Gammex LN300, as the RiFi. The planar integrated dose distribution of a 183.5-MeV/u neon-ion beam was measured behind a 3-cm-thick LN300 plate in water. The Bragg peak of the pristine beam was broadened following the normal distribution with the standard deviation value of 1.29 mm, while the range of the beam was reduced by 8.8 mm by the plate. To verify the LN300 performance as the RiFi in multi-ion therapy, we measured the pencil beam data of helium-, carbon-, oxygen, and neon-ion beams penetrating the 3-cm-thick LN300 plate. The data were then modeled and used in a treatment planning system to achieve a uniform 10% survival of human undifferentiated carcinoma cells within a cuboid target by the beam for each of the different ion species. The measured survival fractions were reasonably reproduced by the planned ones for all the ion species. No surface dose inhomogeneity was observed for any ion species even when the plate was placed close to the phantom surface. The plate made of lung substitute material, Gammex LN300, is applicable as the RiFi in multi-ion therapy with helium-, carbon-, oxygen, and neon-ion beams.

Despite the low contribution of heavy ions to the total fluence in the space radiation environment, their radiobiological effect on the human body is extremely high. In this article, we investigated the radiation field which resulted from the interaction of galactic cosmic rays (GCRs), specifically some heavy ions and energies, typically encountered in space with a realistic multilayer sample of the International Space Station (ISS) Columbus module’s shielding wall. The quality factor, Q, and the normalized dose equivalent, H, derived from microdosimetric measurements for C, Ne, and Si ions behind different spacecraft wall configurations and materials are presented in this article. Particularly, carbon fiber, polyoxymethylene, and perspex with same areal density compared to currently used aluminum were investigated.

Purpose: In carbon ion radiation therapy (CIRT), the dose-averaged LET (LETd) is one of the important factors in determining clinical outcomes. In order to investigate the local control of adenoid cystic carcinoma (ACC) and the optic neuropathy of optic nerve (ON)s in CIRT, the effects of the LETd were evaluated clinically. We propose novel tumor control probability (TCP) and normal tissue complication probability (NTCP) models with D90-value of RBE-weighted dose and LETd as clinical parameters. Methods and Materials: Total 99 patients with head and neck ACC who received CIRT at the National Institute of Radiological Sciences were investigated. The physical dose and LETd distributions for each patient were recalculated using in-house treatment planning system. For ACC tumor, minimum-value of dose-averaged LET and D90-value of RBE-weighted dose as an indicator of evaluation were estimated. For ONs, maximum-value of LETd and maximum-value of RBE-weighted dose were evaluated. Results: For each prescribed RBE-weighted dose of 57.6 and 64 Gy (RBE), no statistical significance for local control by RBE-weighted dose was found, but for 64 Gy (RBE), we observed the LETd may be a marginally significant. For ONs, it was obvious that the optic neuropathy had a greater effect from RBE-weighted dose rather than dose-averaged LET. The proposed models could be applied to both TCP and NTCP prediction, and was found that the clinical outcomes from low to high LETd region were predictable. Conclusions: We analysed clinically the physical dose and LETd distributions for 99 patients with head and neck ACC. Our results indicated that LETd may be a determining factor for local control for ACC tumors. For ON, it was obvious that the RBE-weighted dose was related to optic neuropathy rather than LETd. The proposed approach may be helpful to predict whether LETd will affect clinical outcomes and be useful when constraining not only RBE-weighted dose but also LETd., AAPM2021

The effects of a magnetic field longitudinal to the ion beam track on the generation of hydroxyl radicals (•OH) and hydrogen peroxide (H2O2) in water were investigated. A longitudinal magnetic field was reported to enhance the biological effects of the ion beam. However, the mechanism of the increased cell death by a longitudinal magnetic field has not been clarified. The local density of •OH generation was estimated by a method based on the EPR spin-trapping. A series of reaction mixtures containing varying concentrations (0.76‒2278 mM) of DMPO was irradiated by 16 Gy of carbon- or iron-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan) with or without a longitudinal magnetic field (0.0, 0.3, or 0.6 T). The DMPO-OH yield in the sample solutions was measured by X-band EPR and plotted versus DMPO density. O2-dependent and O2-independent H2O2 yields were measured. An aliquot of ultra-pure water was irradiated by carbon-ion beams with or without a longitudinal magnetic field. Irradiation experiments were performed under air or hypoxic conditions. H2O2 generation in irradiated water samples was quantified by an EPR spin-trapping, which measures •OH synthesized from H2O2 by UVB irradiation. Relatively sparse •OH generation caused by particle beams in water were not affected by loading a magnetic field on the beam track. O2-dependent H2O2 generation decreased and oxygen-independent H2O2 generation increased after loading a magnetic field parallel to the beam track. Loading a magnetic field to the beam track made •OH generation denser or made dense •OH more reactive.

In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak (SOBP) helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator (SOI) microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10×10×6 cm, treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate (PMMA) phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases.

Purpose: For head and neck cancer patients treated with carbon-ion radiotherapy (CIRT), normal tissues such as brain and optic nerve are close to the irradiation field such that those may receive radiation damage. In order to estimate their clinical results, a dose-averaged LET (LETd) calculation tool was developed. We focused on the usefulness of LETd as a clinical analytical parameter. Methods: In-house Heavy Ion Plan (HIPLAN) treatment planning system was used in the CIRT with a wobbler-scattering method. We developed the LETd and its standard deviation (LETdSD) calculation tool, and implemented in the HIPLAN. 33 head and neck patients treated with CIRT, who had follow-up more than 3 years and did not receive additional radiotherapy, were selected in order to evaluate local control and optic neuropathy. LETd and LETdSD for these 33 patients were calculated using the analysis tool. Results: By implementing the clinical analysis tool in HIPLAN, it was possible to efficiently calculate and analyze the LETd and LETdSD for each patient. Of the 33 patients, 13 had local recurrences and 8 had optic neuropathies. Among 33 with and without recurrence cases, the mean LETd values in the PTV were 58.7±5.4 for with recurrence and 61.7±6.9 keV/m for without recurrence, respectively. On the other hand, the mean LETd values were 45.6±12.8 for with optic neuropathy and 29.0±19.0 keV/m for without optic neuropathy (p-value=0.046). Conclusion: We developed the LETd and LETdSD calculation tool and analyzed 33 patients of head and neck cancer for local control and optic neuropathy. Although the mean LETd in the PTV were similar values between cases with and without recurrence, we could observe the usefulness of the LETd analysis for optic neuropathy cases. We will continue to analyze more patients in the future., AAPM2020