Software simulation of tumour motion dose effects during flattened and unflattened ITV-based VMAT lung SBRT

PurposeRestricted studies comparing different dose rate parameters are available while ITV-based VMAT lung SBRT planning leads to perform the analysis of the most suitable parameters of the external beams used. The special emphasis was placed on the impact of dose rate on dose distribution variations in target volumes due to interplay effects.MethodsFour VMAT plans were calculated for 15 lung tumours using 6 MV photon beam quality (flattening filter FF vs. flattening filter free FFF beams) and maximum dose rate of 600 MU/min, 1000 MU/min and 1400 MU/min. Three kinds of motion simulations were performed finally giving 180 plans with perturbed dose distributions.Results6FFF-1400 MUs/min plans were characterized by the shortest beam on time (1.8 ± 0.2 min). Analysing the performed motion simulation results, the mean dose (Dmean) is not a sensitive parameter to related interplay effects. Looking for local maximum and local minimum doses, some discrepancies were found, but their significance was presented for individual patients, not for the whole cohort. The same was observed for other verified dose metrics.ConclusionsGenerally, the evaluation of VMAT robustness between FF and FFF concepts against interplay effect showed a negligible effect of simulated motion influence on tumour coverage among different photon beam quality parameters. Due to the lack of FFF beams, smaller radiotherapy centres are able to perform ITV-based VMAT lung SBRT treatment in a safe way. Radiotherapy department having FFF beams could perform safe, fast and efficient ITV-based VMAT lung SBRT without a concern about significance of interplay effects.     

The effect of beam shape on physical parameters of head and neck simultaneous-integrated boost intensity-modulated radiation therapy

Aim

To evaluate the influence of the beam shape created by X-rays with “flat beams” and without “flattening-filter-free [FFF] beams” a flattening filter, and the isocenter locations for FFF beams on the treatment of a large irradiated volume for tumours.

Photon dose at the maze entrance door: The comparison of flattening filter and flattening filter free working modes

In recent years, field flattening free accelerators have been introduced in therapy practice. One of the objective of these measurements was to establish if the maze door, designed for accelerators operating with flattening filter can provide adequate shielding in field flattening free mode of operation. Linac installed in this standard one band maze vault is equipped to operate at 6 MV with field flattening filter and in field flattening free mode of operation. Series of measurements of the photon dose at the maze door (with different jaws openings and gantry positions) were performed in both operation modes with and without water canister to mimic standard therapy conditions. In this paper results of photon dose measurements, performed at the maze door of the therapy linear accelerator vault are presented in order to compare photon dose in flattening filter and flattening filter free operation modes. It was obtained that in field flattening free mode of operation, the dose at the maze door is always lower than the dose measured in standard mode of operation with the field flattening filter. In the case when FFF therapy practice should start in some existing therapy vault, no additional shielding measures need to be added at the existing maze door.     

A novel high-resolution 2D silicon array detector for small field dosimetry with FFF photon beams

PurposeFlattening filter free (FFF) beams are increasingly being considered for stereotactic radiotherapy (SRT). For the first time, the performance of a monolithic silicon array detector under 6 and 10 MV FFF beams was evaluated. The dosimeter, named “Octa” and designed by the Centre for Medical Radiation Physics (CMRP), was tested also under flattened beams for comparison.MethodsOutput factors (OFs), percentage depth-dose (PDD), dose profiles (DPs) and dose per pulse (DPP) dependence were investigated. Results were benchmarked against commercially available detectors for small field dosimetry.ResultsThe dosimeter was shown to be a ‘correction-free’ silicon array detector for OFs and PDD measurements for all the beam qualities investigated. Measured OFs were accurate within 3% and PDD values within 2% compared against the benchmarks. Cross-plane, in-plane and diagonal DPs were measured simultaneously with high spatial resolution (0.3 mm) and real time read-out. A DPP dependence (24% at 0.021 mGy/pulse relative to 0.278 mGy/pulse) was found and could be easily corrected for in the case of machine specific quality assurance applications.ConclusionsResults were consistent with those for monolithic silicon array detectors designed by the CMRP and previously characterized under flattened beams only, supporting the robustness of this technology for relative dosimetry for a wide range of beam qualities and dose per pulses. In contrast to its predecessors, the design of the Octa offers an exhaustive high-resolution 2D dose map characterization, making it a unique real-time radiation detector for small field dosimetry for field sizes up to 3 cm side.     

Analysis of physical parameters and determination of inflection point for Flattening Filter Free beams in medical linear accelerator

Background

Medical Linear accelerators manufactured without flattening filters are increasing popular in recent days. The removal of flattening filter results in increased dose rate, reduced mean energy, reduction in head leakage and lateral scattering, which have shown advantageous when used for special treatment procedures.

Aim

This study aims to analyze physical parameters of FFF beams and to determine the inflection point for standardizing the beam flatness and penumbra.

Materials and methods

The beam profiles and depth dose patterns were measured using Radiation Field Analyzer (RFA) with 0.13 cc cylindrical ion chamber. The beam energy characteristics, head scatter factor (Sc) were obtained for 6FFF and 10FFF beams and compared with 6 MV and 10 MV photons, respectively. The symmetry and stability of unflattened regions were also analyzed. In addition, the study proposes a simple physical concept for obtaining inflection point for FFF beams and results were compared using the Akima spline interpolation method. The inflection point was used to determine the field size and penumbra of FFF beams.

Results

The Sc varied from 0.922 to 1.044 for 6FFF and from 0.913 to 1.044 for 10FFF with field sizes from 3 cm × 3 cm to 40 cm × 40 cm which is much less than FF beams. The obtained value of field size and penumbra for both simple physical concept and Akima spline interpolation methods is within the ±1.0 mm for the field size and ±2 mm penumbra. The results indicate that FFF beams reduce Sc compared with FF beams due to the absence of a flattening filter.

Conclusion

The proposed simple method to find field size and penumbra using inflection point can be accepted as it is closely approximated to mathematical results. Stability of these parameters was ascertained by repeated measurements and the study indicates good stability for FFF beam similar to that of FF beams.     

Molecular mass sorting of proteome using hollow fiber flow field-flow fractionation for proteomics

Hollow fiber flow field-flow fractionation (HF FlFFF) has been demonstrated as a tool for pre-fractionating proteomes by differences in molecular mass (Mr), where the resulting protein fractions are subsequently digested and analyzed by shotgun proteomics using two-dimensional liquid chromatography-electrospray ionization-tandem mass spectrometry (2D-LC-ESI-MS/MS). HF FlFFF is a separation device capable of fractionating proteins or cells by hydrodynamic radius, and protein fraction can be readily collected as intact conditions in aqueous buffer solutions. In this study, HF FlFFF was applied to fractionate the proteome of Corynebacterium glutamicum, a well known soil bacterium that has been widely used in bioindustry due to its remarkable ability to secrete high amounts of glutamic acid. The collected HF FlFFF fractions of different MW intervals were enzymatically digested for protein identification by 2D-LC-ESI-MS/MS. Experiments showed improvements in protein identification when HF FlFFF pre-fractionation was applied, due to decreases in the ionization suppression effect and the MS exclusion effect by spectral congestion. Pre-fractionation of C. glutamicum proteome allowed us to find 90 additional proteins by 2D-LC-ESI-MS/MS that were not found by a direct shotgun analysis without pre-fractionation. A total of 415 proteins were found overall with 203 proteins commonly found from experiments with and without pre-fractionation.     

The use of sedimentation field-flow fractionation to study suspended particulate matter

The current and potential uses of sedimentation field-flow fractionation (SdFFF) for characterizing suspended particulate matter (SPM) from natural waters is reviewed. Suitable sample preparation methods and run conditions are given which enable the particle size distribution of aquatic SPM to be determined. Samples collected from different natural waters display quite distinct differences in the shape of their particle size distribution.One of the major advantages of this high resolution separation technique is that fractions of specific size ranges can be collected for characterization by other analytical methods. This has been illustrated in this work with scanning electron microscopy and EDAX elemental analysis data. The potential to extend this approach using other characterization techniques such as inductively coupled-plasma mass spectrometry and X-ray diffraction is discussed.A method has been developed for combining adsorption experiments with SdFFF separations that enables the distributions of both the amount adsorbed and the surface adsorption density across the SPM size range to be determined with good resolution. This approach is illustrated by the adsorption of the herbicide glyphosate to two estuarine SPM samples.     

Dose response of a radiophotoluminescent glass dosimeter for TomoTherapy,CyberKnife, and flattening-filter-free linear accelerator output measurements in dosimetry audit

PurposeWe experimentally determined the radiophotoluminescent glass dosimeter (RPLD) dose responses for TomoTherapy, CyberKnife, and flattening-filter-free (FFF) linear accelerator (linac) outputs for dosimetry audits in Japan.MethodsA custom-made solid phantom with a narrow central-axis spacing of three RPLD elements was used for output measurement to minimise the dose-gradient effect of the non-flattening filter beams. For RPLD dose estimation, we used the ISO 22127 formalism. Additional unit-specific correction factors were introduced and determined via the measured data. For TomoTherapy (7 units) and CyberKnife (4 units), the doses were measured under machine-specific reference fields. For FFF linac (5 units), in addition to the reference condition, we obtained the field-size effects for the range from 5×5 cm to 25×25 cm.ResultsThe correction factors were estimated as 1.008 and 0.999 for TomoTherapy and CyberKnife, respectively. For FFF linac, they ranged from 1.011 to 0.988 for 6 MV and from 1.011 to 0.997 for 10 MV as a function of the side length of the square field from 5 to 25 cm. The estimated uncertainties of the absorbed dose to water measured by RPLD for the units were 1.32%, 1.35%, and 1.30% for TomoTherapy, CyberKnife, and FFF linac, respectively. A summary of the dosimetry audits of these treatment units using the obtained correction factors is also presented. The average percentage differences between the measured and hospital-stated doses were <1% under all conditions.ConclusionRPLD can be successfully used as a dosimetry audit tool for modern treatment units.     

Advances in Lead Generation

Lead Generation represents a critical drug discovery phase where chemical starting points and their respective mechanism of action, quality, and potential liabilities are largely predefined. Recent advances such as DNA-encoded libraries or fragment-, chemical biology-, and virtual screening-based approaches are today as common as traditional High Throughput Screening. Innovations in characterizing lead quality have allowed more informed decision-making by discovery teams. The key challenge today is to individually tailor the right mix of methods for each project to facilitate data integration with the purpose of creating multiple high-quality lead series, ultimately translating to reduced chemistry-related pipeline attrition.