Evaluation of in vitro irradiation setup: Designed for the horizontal beamline at the Danish Centre for Particle Therapy.

BACKGROUND: Radiobiological experimental setups are challenged by precise sample positioning along depth dose profile, scattering conditions, and practical difficulties that must be addressed in individual designs. The aim of this study was to produce cell survival curves with several irradiation modalities, by using a setup designed at the Danish Centre for Particle Therapy (DCPT) for in vitro proton irradiations using a horizontal beam line and thereby evaluating the setups use for in vitro irradiations experiments. MATERIALS AND METHODS: The setup is a water phantom suitable for in vitro research with multiple irradiation modalities, in particular the pencil scanning proton beam available from a horizontal experimental beamline. The phantom included a water tank of 39.0 × 17.0 × 20.5 cm. Cell survival-curves were produced using the cell line V79 Chinese hamster lung fibroblast cells (V79s) in biological triplicates of clonogenic assays. Cell survival curves were produced with both a 18 MeV electron beam, 6 MV photon beam, and a Spread-Out Bragg Peak (SOBP) proton beam formed by pristine energies of 85-111 MeV where three positions were examined. RESULTS: Survival curves with uncertainty areas were made for all modalities. Dosimetric uncertainty amounted to, respectively, 4%, 3% and 3% for proton, electron, and high energy photon irradiations. Cell survival fraction uncertainty was depicted as the standard deviation between replications of the experiment. CONCLUSION: Cell survival curves could be produced with acceptable uncertainties using this novel water phantom and cellular laboratory workflow. The setup is useful for future in vitro irradiation experiments.

Technical note: Temporal and thermal stability of optical response for silicone-based 3D radiochromic dosimeters.

BACKGROUND: Radiochromic silicone-based dosimeters are flexible 3D dosimeters, which at appropriate concentration of leucomalachite green (LMG) and curing agent are dose-rate independent for clinical photon beams. However, their dose response is based on chemical processes that can be influenced by temporal and thermal conditions, impacting measurement stability. PURPOSE: The aim of this study was to investigate the temporal stability of the dose response of radiochromic dosimeters for different curing times and post-irradiation storage temperatures. METHODS: Six cylindrical dosimeters (5 cm diameter, 5 cm length) were produced in a single batch and separated into two groups that were irradiated 72 and 118 h after production. The same photon plan, consisting of two 10 × 1.6 cm2 opposing fields, was delivered to all dosimeters. After irradiation, the dosimeters were separated into three groups, stored at 5°C, 15°C, and 20°C, and read out for five consecutive days. RESULTS: Storage temperature influenced the measurement stability, and changes in the optical response with time differed between irradiated and non-irradiated parts of the dosimeters. The relative change between signal and background was greater than 10% for all measurements performed 24 h or more after irradiation, except for dosimeters stored at 5°C, which changed by 2%-5% after 24 h. The dosimeter temporal stability was not influenced by curing time. CONCLUSIONS: For room temperature storage (15°C and 20°C), readout should take place as soon as possible after irradiation since the background color increased rapidly for both curing times (72 and 118 h), whereas the dosimeters are stored at 5°C, readout can be performed up to 24 h after.

An Intracortical Implantable Brain-Computer Interface for Telemetric Real-Time Recording and Manipulation of Neuronal Circuits for Closed-Loop Intervention.

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces (BCIs) should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions.

Radionecrosis and cellular changes in small volume stereotactic brain radiosurgery in a porcine model.

Stereotactic radiosurgery (SRS) has proven an effective tool for the treatment of brain tumors, arteriovenous malformation, and functional conditions. However, radiation-induced therapeutic effect in viable cells in functional SRS is also suggested. Evaluation of the proposed modulatory effect of irradiation on neuronal activity without causing cellular death requires the knowledge of radiation dose tolerance at very small tissue volume. Therefore, we aimed to establish a porcine model to study the effects of ultra-high radiosurgical doses in small volumes of the brain. Five minipigs received focal stereotactic radiosurgery with single large doses of 40-100 Gy to 5-7.5 mm fields in the left primary motor cortex and the right subcortical white matter, and one animal remained as unirradiated control. The animals were followed-up with serial MRI, PET scans, and histology 6 months post-radiation. We observed a dose-dependent relation of the histological and MRI changes at 6 months post-radiation. The necrotic lesions were seen in the grey matter at 100 Gy and in white matter at 60 Gy. Furthermore, small volume radiosurgery at different dose levels induced vascular, as well as neuronal cell changes and glial cell remodeling.