Background and Aims

To date, single dose and hypo-fractionated regimens of whole brain FLASH-RT have been shown to reduce the adverse cognitive and pathological complications routinely observed after conventional dose rate radiotherapy (CONV-RT). In this study, our aim was to evaluate the impact of a standard fractionation regimen on brain function.

Methods

Whole brain 3Gy fractions were delivered daily using CONV and FLASH (eRT6/Oriatron) for two weeks (10x3Gy) and long-term potentiation (LTP) was used to provide direct readouts of neurotransmission. While behavioral testing remains the gold standard for validating the functional impact of cranial irradiation on the brain, electrophysiological assessments and LTP are direct measurements of synaptic plasticity.

Results

Our previous results in pediatric and adult mouse models showed that consistently with neurocognitive preservation, LTP was preserved after FLASH-RT when delivered in single and hypo-fractionated regimens but was significantly inhibited after CONV-RT. In this study, data collected from two regions of the brain (hippocampus, medial prefrontal cortex) confirmed significant inhibition of LTP after 10x3Gy CONV-RT. Remarkably, 10x3Gy FLASH-RT and controls were identical and exhibited normal LTP across each brain region.

Conclusions

While further work is ongoing to establish a causal link between LTP and behavioral outcomes and validate the anti-tumor effect, these results provide the first evidence that brain functionality is preserved after standard fractionation with FLASH-RT.

Background and Aims

Knowledge of the delivered beam in Proton minibeam radiation therapy (pMBRT) is essential for predicting the outcome of a given treatment. This is not possible with conventional on-line beam monitoring equipment which lacks the dynamic range and spatial resolution for verification of in pMBRT in real-time.

This study aimed for the first time to investigate whether CMOS detectors are suitable instruments for measuring pMBRT at clinical dose rates in a pencil beam scanning proton setp-up; to determine what technological developments are required to perform real-time quality assurance or beam monitoring in such beams.

Methods

The vM2428 detector, a large-format CMOS detector with 50μm pixel pitch, was exposed to 100MeV 400 μm planar minibeams at the Institute Curie, Orsay. By placing EBT3XD film directly on top of the CMOS’ active area, a direct comparison could be made between the two detectors. Both a single irradiation position (representing a single component of a scanned beam delivery) and a scanned delivery over a 5x5cm² field size were investigated.

Results

Saturation of the pixel response was found to be an issue, requiring the implementation of a narrow Region-of-Interest (ROI) in order to capture the full beam. Using a single frame of the CMOS detector: two instruments found agreement for single beam position (Figure 1); with the vM2428 detector able to measure relative peak heights, separations and PVDR in a fraction of the time required for film.

Figure 1: Profile comparison of the CMOS detector and radiochromic film.

Figure 2: CMOS frames acquired during pMBRT delivery

Two dimensional beam position and intensity data acquired by the CMOS detector during the irradiation (Figure 2) was found to agree with the treatment planning logs.

Conclusions

CMOS technology is a viable candidate for beam monitoring in pMBRT, with tests to further reduce pixel saturation and exploit other CMOS properties currently being planned.

Background and Aims

The physical properties of silicon carbide (SiC) make it a very promising material for radiation dosimetry in ultra-high dose rate (UHDR) pulsed beams. SiC has a mature technology allowing to produce complex and reproducible structures and a good price-performance ratio. However at the moment SiC radiation dosimeters do not exist in the commercial market.

Methods

Circular 1mm diameter SiC PiN diodes were fabricated at CNM-CSIC in 3 μm epitaxial 4H-SiC. Selected diodes were encapsulated by PTW Freiburg with their commercial microSilicon housing to provide electrical connectivity.

Diode characterization was performed in PTB’s ultra-high pulse dose rate reference electron beam with a dose per pulse (DPP) up to 11 Gy (20 MeV, 3 μs, 1.5 μs and 0.6 μs pulse duration, 5 Hz repetition frequency). The SiC diode was positioned in a motorized water phantom and was operated without external bias voltage. A diamond prototype detector (flashDiamond) and Alanine measurements were used for reference dosimetry.

Results

At dose per pulse (DPP) up to 0.45Gy/pulse with pulse durations of 2.9 or 1.5 μs, the SiC diode showed independence both of DPP and of instantaneous dose rate with a linearity deviation of less than 0.8% including reference dose measurement uncertainty.

At higher DPPs, well into the FLASH regime, the diode was linear up to at least 11Gy/pulse with a relative deviation of <1% (Fig.1).

The sensitivity reduction after 100kGy accummulated dose was 5%. When measuring the percentage depth dose under UHDR conditions, the SiC diode performed comparably well to the reference flashDiamond.

Conclusions

We have demonstrated for the first time the suitability of SiC diodes for relative dosimetry in UHDR pulsed electron beams up to a DPP of 11Gy.

This work has received funding from the Spanish State Research Agency and the European Regional Development Fund under project RTC-2017-6369-3, and from the EMPIR programme under project 18HLT04-UHDpulse.