Characterization of Inorganic Scintillator Detectors for Dosimetry in Image-Guided Small Animal Radiotherapy Platforms

The purpose of the study was to characterize a detection system based on inorganic scintillators and determine its suitability for dosimetry in preclinical radiation research. Dose rate, linearity, and repeatability of the response (among others) were assessed for medium-energy X-ray beam qualities. The response's variation with temperature and beam angle incidence was also evaluated. Absorbed dose quality-dependent calibration coefficients, based on a cross-calibration against air kerma secondary standard ionization chambers, were determined. Relative output factors (ROF) for small, collimated fields (≤10 mm × 10 mm) were measured and compared with Gafchromic film and to a CMOS imaging sensor. Independently of the beam quality, the scintillator signal repeatability was adequate and linear with dose. Compared with EBT3 films and CMOS, ROF was within 5% (except for smaller circular fields). We demonstrated that when the detector is cross-calibrated in the user's beam, it is a useful tool for dosimetry in medium-energy X-rays with small fields delivered by Image-Guided Small Animal Radiotherapy Platforms. It supports the development of procedures for independent "live" dose verification of complex preclinical radiotherapy plans with the possibility to insert the detectors in phantoms

Determination of beam quality correction factors for the Roos plane-parallel ionisation chamber exposed to very high energy electron (VHEE) beams using Geant4

Detailed characterisation of the Roos secondary standard plane-parallel ionisation chamber has been conducted in a novel 200 MeV Very High Energy Electron (VHEE) beam with reference to the standard 12 MeV electron calibration beam used in our experimental work. Stopping-power-ratios and perturbation factors have been determined for both beams and used to calculated the beam quality correction factor using the Geant4 general purpose MC code. These factors have been calculated for a variety of charged particle transport parameters available in Geant4 which were found to pass the Fano cavity test. Stopping-power-ratios for the 12 MeV electron calibration beam quality were found to agree within uncertainties to that quoted by current dosimetry protocols. Perturbation factors were found to vary by up-to 4% for the calibration beam depending on the parameter configuration, compared with only 0.8% for the VHEE beam. Beam quality correction factors were found to describe an approximately 10% lower dose than would be originally calculated if a beam quality correction were not accounted for. Moreover, results presented here largely resolve unphysical chamber measurements, such as collection efficiencies greater than 100%, and assist in the accurate determination of absorbed dose and ion recombination in secondary standard ionisation chambers

Challenges of dosimetry of ultra-short pulsed very high energy electron beams

Very high energy electrons (VHEE) in the range from 100–250 MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetric properties compared with 6-20 MV photons generated by clinical linear accelerators (LINACs). VHEE beams have characteristics unlike any other beams currently used for radiotherapy: femtosecond to picosecond duration electron bunches, which leads to very high dose per pulse, and energies that exceed that currently used in clinical applications. Dosimetry with conventional online detectors, such as ionization chambers or diodes, is a challenge due to non-negligible ion recombination effects taking place in the sensitive volumes of these detectors. FLUKA and Geant4 Monet Carlo (MC) codes have been employed to study the temporal and spectral evolution of ultrashort VHEE beams in a water phantom. These results are complemented by ion recombination measurements employing an IBA CC04 ionization chamber for a 165 MeV VHEE beam. For comparison, ion recombination has also been measured using the same chamber with a conventional 20 MeV electron beam. This work demonstrates that the IBA CC04 ionization chamber exhibits significant ion recombination and is therefore not suitable for dosimetry of ultrashort pulsed VHEE beams applying conventional correction factors. Further study is required to investigate the applicability of ion chambers in VHEE dosimetry

Dosimetry for new radiation therapy approaches using high energy electron accelerators

We have performed dosimetry studies using electron beams with energies up to 50 MeV, which exceed current clinical energy ranges and approaches the bottom end of the very high energy electron range. 50 MeV electron beams can reach deep-seated tumors. In contrast to photon beams, electron beams can be generated with ultra-high dose rates by linear accelerators, which could enable FLASH radiotherapy of deep-seated tumors. The response of radiochromic film and alanine is compared with dose measurements using an ionisation chamber. Energy dependence is not observed within the measurement uncertainty in the investigated energy range from 15 to 50 MeV

Development of an anatomically correct mouse phantom for dosimetry measurement in small animal radiotherapy research

Significant improvements in radiotherapy are likely to come from biological rather than technical optimization, for example increasing tumour radiosensitivity via combination with targeted therapies. Such paradigms must first be evaluated in preclinical models for efficacy, and recent advances in small animal radiotherapy research platforms allow advanced irradiation protocols, similar to those used clinically, to be carried out in orthotopic models. Dose assessment in such systems is complex however, and a lack of established tools and methodologies for traceable and accurate dosimetry is currently limiting the capabilities of such platforms and slowing the clinical uptake of new approaches. Here we report the creation of an anatomically correct phantom, fabricated from materials with tissue-equivalent electron density, into which dosimetry detectors can be incorporated for measurement as part of quality control (QC). The phantom also allows training in preclinical radiotherapy planning and cross-institution validation of dose delivery protocols for small animal radiotherapy platforms without the need to sacrifice animals, with high reproducibility.Mouse CT data was acquired and segmented into soft tissue, bone and lung. The skeleton was fabricated using 3D printing, whilst lung was created using computer numerical control (CNC) milling. Skeleton and lung were then set into a surface-rendered mould and soft tissue material added to create a whole-body phantom. Materials for fabrication were characterized for atomic composition and attenuation for x-ray energies typically found in small animal irradiators. Finally cores were CNC milled to allow intracranial incorporation of bespoke detectors (alanine pellets) for dosimetry measurement

Characterization of laser-driven single and double electron bunches with a permanent magnet quadrupole triplet and pepper-pot mask

Electron beams from laser-plasma wakefield accelerators have low transverse emittance, comparable to those from conventional radio frequency accelerators, which highlights their potential for applications, many of which will require the use of quadrupole magnets for optimal electron beam transport. We report on characterizing electron bunches where double bunches are observed under certain conditions. In particular, we present pepper-pot measurements of the transverse emittance of 120-200 MeV laser wakefield electron bunches after propagation through a triplet of permanent quadrupole magnets. It is shown that the normalized emittance at source can be as low as 1 π mm mrad (resolution limited), growing by about five times after propagation through the quadrupoles due to beam energy spread. The inherent energy-dependence of the magnets also enables detection of double electron bunches that could otherwise remain unresolved, providing insight into the self-injection of multiple bunches. The combination of quadrupoles and pepper-pot, in addition, acts as a diagnostic for the alignment of the magnetic triplet

Evaluation of a pixelated large format CMOS sensor for x-ray microbeam radiotherapy

PURPOSE: Current techniques and procedures for dosimetry in microbeams typically rely on radiochromic film or small volume ionization chambers for validation and quality assurance in 2D and 1D, respectively. Whilst well characterized for clinical and preclinical radiotherapy, these methods are noninstantaneous and do not provide real time profile information. The objective of this work is to determine the suitability of the newly developed vM1212 detector, a pixelated CMOS (complementary metal-oxide-semiconductor) imaging sensor, for in situ and in vivo verification of x-ray microbeams.METHODS: Experiments were carried out on the vM1212 detector using a 220 kVp small animal radiation research platform (SARRP) at the Helmholtz Centre Munich. A 3 x 3 cm2 square piece of EBT3 film was placed on top of a marked nonfibrous card overlaying the sensitive silicon of the sensor. One centimeter of water equivalent bolus material was placed on top of the film for build-up. The response of the detector was compared to an Epson Expression 10000XL flatbed scanner using FilmQA Pro with triple channel dosimetry. This was also compared to a separate exposure using 450 µm of silicon as a surrogate for the detector and a Zeiss Axio Imager 2 microscope using an optical microscopy method of dosimetry. Microbeam collimator slits with range of nominal widths of 25, 50, 75, and 100 µm were used to compare beam profiles and determine sensitivity of the detector and both film measurements to different microbeams.RESULTS: The detector was able to measure peak and valley profiles in real-time, a significant reduction from the 24 hr self-development required by the EBT3 film. Observed full width at half maximum (FWHM) values were larger than the nominal slit widths, ranging from 130 to 190 µm due to divergence. Agreement between the methods was found for peak-to-valley dose ratio (PVDR), peak to peak separation and FWHM, but a difference in relative intensity of the microbeams was observed between the detectors.CONCLUSIONS: The investigation demonstrated that pixelated CMOS sensors could be applied to microbeam radiotherapy for real-time dosimetry in the future, however the relatively large pixel pitch of the vM1212 detector limit the immediate application of the results.</p

Defining robustness protocols: a method to include and evaluate robustness in clinical plans.

This is the final version of the article. It first appeared from IOP Publishing via http://dx.doi.org/10.1088/0031-9155/60/7/2671We aim to define a site-specific robustness protocol to be used during the clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to systematic range and random set-up errors have been retrospectively and systematically analysed. This was determined by calculating the error-bar dose distribution (ebDD) for all the plans and by defining some metrics used to define protocols aiding the plan assessment. Additionally, an example of how to clinically use the defined robustness database is given whereby a plan with sub-optimal brainstem robustness was identified. The advantage of using different beam arrangements to improve the plan robustness was analysed. Using the ebDD it was found range errors had a smaller effect on dose distribution than the corresponding set-up error in a single fraction, and that organs at risk were most robust to the range errors, whereas the target was more robust to set-up errors. A database was created to aid planners in terms of plan robustness aims in these volumes. This resulted in the definition of site-specific robustness protocols. The use of robustness constraints allowed for the identification of a specific patient that may have benefited from a treatment of greater individuality. A new beam arrangement showed to be preferential when balancing conformality and robustness for this case. The ebDD and error-bar volume histogram proved effective in analysing plan robustness. The process of retrospective analysis could be used to establish site-specific robustness planning protocols in proton therapy. These protocols allow the planner to determine plans that, although delivering a dosimetrically adequate dose distribution, have resulted in sub-optimal robustness to these uncertainties. For these cases the use of different beam start conditions may improve the plan robustness to set-up and range uncertainties.This work was partly funded by an MRC Doctoral Training Grant

Feasibility studies on the application of relativistic electron beams from a laser plasma wakefield accelerator in radiotherapy

Very high energy electrons (VHEEs) (100-250 MeV) have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetry properties compared with X-ray photons, which could confer possible radiobiological benefits. The rapid development of ultra-compact laser-plasma wakefield accelerators (LWFAs) is now providing a potential low cost device for VHEE radiotherapy. These beams have characteristics unlike any other beams currently used for radiotherapy: femotosecond radiation pulses, small field size and energies that exceed electron energies currently used in clinical applications. A set of Monte Carlo (MC) calculations have been performed to study dosimetric properties of VHEEs propagating in water. To assess radiation protection and safety handling issues, the generation of neutrons, induced activity and equivalent doses have been evaluated. A dosimetry system, consisting of EBT2 Gafchromic® film and EPSON Expression 10000XL scanner, for VHEEs has been established. EBT2 Gafchromic film turns out to be a robust dosimeter with a minor energy-dependent response over a broad range of beam energies and modalities, and can be successfully used for dosimetry of very high energy electron beams. The dosimetric measurements have been carried out using three different accelerators: a 20 MeV clinical LINAC, a 165 MeV conventional LINAC and a 135 MeV laser-plasma wakefield accelerator. The measurements have been compared with Monte Carlo simulations using the FLUKA code. Additionally, the set of dose measurements employing IBA CC04 ionisation chamber has been presented. Dosimetric measurements have been complemented by preliminary cancer cell irradiation studies to determine the toxicity and dose response to LWFA VHEEs of two lung cancer cell lines (A549 and H460). The efficacy of VHEEs on in vitro tumour cells has been assessed by clonogenic assay and γ-H2AX assay employing immunofluorescence detection of signalling molecules has been deployed to indicate DNA double-strand breaks and repair.Very high energy electrons (VHEEs) (100-250 MeV) have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetry properties compared with X-ray photons, which could confer possible radiobiological benefits. The rapid development of ultra-compact laser-plasma wakefield accelerators (LWFAs) is now providing a potential low cost device for VHEE radiotherapy. These beams have characteristics unlike any other beams currently used for radiotherapy: femotosecond radiation pulses, small field size and energies that exceed electron energies currently used in clinical applications. A set of Monte Carlo (MC) calculations have been performed to study dosimetric properties of VHEEs propagating in water. To assess radiation protection and safety handling issues, the generation of neutrons, induced activity and equivalent doses have been evaluated. A dosimetry system, consisting of EBT2 Gafchromic® film and EPSON Expression 10000XL scanner, for VHEEs has been established. EBT2 Gafchromic film turns out to be a robust dosimeter with a minor energy-dependent response over a broad range of beam energies and modalities, and can be successfully used for dosimetry of very high energy electron beams. The dosimetric measurements have been carried out using three different accelerators: a 20 MeV clinical LINAC, a 165 MeV conventional LINAC and a 135 MeV laser-plasma wakefield accelerator. The measurements have been compared with Monte Carlo simulations using the FLUKA code. Additionally, the set of dose measurements employing IBA CC04 ionisation chamber has been presented. Dosimetric measurements have been complemented by preliminary cancer cell irradiation studies to determine the toxicity and dose response to LWFA VHEEs of two lung cancer cell lines (A549 and H460). The efficacy of VHEEs on in vitro tumour cells has been assessed by clonogenic assay and γ-H2AX assay employing immunofluorescence detection of signalling molecules has been deployed to indicate DNA double-strand breaks and repair