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6CCVD Research

Design and dosimetric characterization of a transportable proton minibeam collimation system

At a Glance

Section titled “At a Glance”
MetadataDetails
Publication Date2024-12-17
JournalFrontiers in Oncology
AuthorsMabroor Ahmed, Elke Beyreuther, Sebastian Gantz, Felix Horst, Juergen Meyer
InstitutionsHelmholtz-Zentrum Dresden-Rossendorf, Klinikum rechts der Isar
Citations1
AnalysisFull AI Review Included

Executive Summary

Section titled “Executive Summary”

This research details the design, optimization, and dosimetric validation of a novel, transportable mechanical collimation system for Proton Minibeam Radiation Therapy (pMBRT).

  • Core Achievement: Successfully generated narrow proton minibeams (250”m width, 1000”m ctc) with high spatial modulation, achieving a Peak-to-Valley Dose Ratio (PVDR) of 10 (150 MeV beam) and 14 (50.5 MeV beam) at 5mm phantom depth.
  • Design Optimization: Monte Carlo simulations (TOPAS/Geant4) were critical for optimizing brass collimator geometry and Polymethymethacrylate (PMMA) block thickness to maximize PVDR and ensure lateral dose uniformity.
  • Transportability: The system was validated at two distinct proton facilities (Dresden and Seattle) using different energies (150 MeV and 50.5 MeV), confirming its flexibility and suitability for inter-institutional comparative studies.
  • Dosimetry Validation: EBT3 radiochromic film dosimetry was used as the reference standard, confirming the minibeam dimensions (FWHM 265-320 ”m) and PVDRs.
  • Online Dosimetry Investigation: The microDiamond detector (PTW 60019) was tested for online dosimetry, showing excellent agreement in the valley regions but significantly overestimating the peak dose (up to 21% discrepancy at 50.5 MeV).
  • Engineering Implication: The microDiamond discrepancy highlights the need for position-specific radiation correction factors when using solid-state detectors in highly non-uniform minibeam fields.

Technical Specifications

Section titled “Technical Specifications”
ParameterValueUnitContext
Target Minibeam Width250”mDesign specification
Center-to-Center (ctc) Distance1000”mDesign specification
Achieved PVDR (150 MeV)10RatioMeasured at 5mm depth in PMMA (Film)
Achieved PVDR (50.5 MeV)14RatioMeasured at 5mm depth in PMMA (Film)
FWHM (150 MeV)265”mMeasured with EBT3 film
FWHM (50.5 MeV)320”mMeasured with EBT3 film
Proton Energy (Dresden)150MeVUniversity Proton Therapy Dresden
Proton Energy (Seattle)50.5MeVUniversity of Washington Medical Center
Collimator MaterialBrassN/APre-collimator and Minibeam Collimator
Minibeam Collimator Thickness5cmBrass block with 11 slits
Pre-Collimator Slit Opening4mmOptimized via TOPAS simulation
PMMA Block Thickness (150 MeV)4cmUsed for beam homogenization
PMMA Block Thickness (50.5 MeV)0.5cmUsed for beam homogenization
Air Gap (Collimator to Target)10mmFixed experimental distance
MicroDiamond Peak Discrepancy9.5%Overestimation vs. film (150 MeV)
MicroDiamond Peak Discrepancy21%Overestimation vs. film (50.5 MeV)
Initial Proton Loss Rate99.5%Protons lost during selection process

Key Methodologies

Section titled “Key Methodologies”
  1. Monte Carlo Optimization: TOPAS (Version 3.6) simulations utilizing Geant4 physics lists were employed to model the 150 MeV beam. Optimization focused on maximizing PVDR by adjusting the pre-collimator slit opening (selected 4 mm) and the collimator distance (selected 1 m).
  2. Collimator Fabrication: Both the pre-collimator and the minibeam collimator were constructed from brass. The minibeam collimator (5 cm thick) featured 11 slits, tilted to align with the divergence of the incoming beam.
  3. Beam Homogenization: Energy-dependent PMMA blocks were inserted between the collimators (4 cm for 150 MeV; 0.5 cm for 50.5 MeV) to ensure a uniform proton distribution at the minibeam collimator surface, guaranteeing equal dose delivery across all minibeams.
  4. Angular Alignment: Components were mounted on high-precision rotational stages (OWIS LTM 80-75-HSM). Alignment was achieved by iteratively maximizing the beam intensity measured by a fluorescent detector (Lynx or webcam sheet readout), requiring angular precision down to 0.2°.
  5. Reference Dosimetry (Film): Gafchromic EBT3 films were calibrated (0-10 Gy) using a homogeneous proton field and a Markus Chamber. Dose profiles were acquired at 5 mm depth in PMMA. Due to dynamic range limitations, two films were irradiated per profile (one for peak, one for valley) and stitched together.
  6. Online Dosimetry (MicroDiamond): A PTW 60019 microDiamond detector, operated in edge-on mode for high spatial resolution, was cross-calibrated against the Markus Chamber. The detector was stepped through the minibeam field with a 20 ”m step size using motorized stages (OWIS or Mecademic robot arm) to acquire real-time dose profiles.

Commercial Applications

Section titled “Commercial Applications”

The developed transportable pMBRT system and its associated high-resolution dosimetry protocol are critical for advancing pre-clinical research and standardization in radiation therapy.

  • Pre-clinical Radiation Therapy: Essential for conducting standardized in vitro and in vivo small animal studies (e.g., mouse models) to define the optimal physical parameters (PVDR, FWHM, ctc) required for therapeutic efficacy and normal tissue sparing in pMBRT.
  • Advanced Dosimetry and QA: The methodology provides a robust testbed for characterizing the response of novel detectors (like the microDiamond) in highly non-uniform, high-gradient dose fields, crucial for quality assurance (QA) in spatially fractionated techniques.
  • Particle Accelerator Research: The transportable design allows different proton therapy facilities (cyclotrons, synchrotrons) to compare beam quality and experimental results directly, accelerating the understanding of energy dependence in pMBRT.
  • Future Clinical Nozzle Design: The data on PVDR limitations and proton loss rates (99.5% loss) inform the engineering requirements for future clinical pMBRT nozzles, suggesting a shift toward magnetic focusing systems to mitigate scattering losses inherent in mechanical collimation.
View Original Abstract

Background Proton Minibeam Radiation Therapy has shown to widen the therapeutic window compared to conventional radiation treatment in pre-clinical studies. The underlying biological mechanisms, however, require more research. Purpose The purpose of this study was to develop and characterize a mechanical collimation setup capable of producing 250”m wide proton minibeams with a center-to-center distance of 1000”m. Methods To find the optimal arrangement Monte Carlo simulations were employed using the Geant4 toolkit TOPAS to maximize key parameters such as the peak-to-valley dose ratio (PVDR) and the valley dose rate. The experimental characterization of the optimized setup was carried out with film dosimetry at the University Proton Therapy beamline in Dresden and the proton beamline of the University of Washington Medical Center in Seattle with 150MeV and 50.5MeV, respectively. A microDiamond detector (PTW, Freiburg, Germany) was utilized at both beamlines for online proton minibeam dosimetry. Results A PVDR of 10 was achieved in Dresden and a PVDR of 14 in Seattle. Dosimetry measurements were carried out with EBT3 films at a depth of 5mm in a polymethylmethacrylate (PMMA) phantom. When comparing film dosimetry with the microDiamond, excellent agreement was observed in the valleys. However, the peak dose showed a discrepancy of approximately 10% in the 150MeV beam and 20% in the 50.5MeV beam between film and microDiamond. Discussion The characteristics of the minibeams generated with our system compares well with those of other collimated minibeams despite being smaller. The deviations of microDiamond measurements from film readings might be subject to the diamond detector responding differently in the peak and valley regions. Applying previously reported correction factors aligns the dose profile measured by the microDiamond with the profile acquired with EBT3 films in Dresden. Conclusion The novel proton minibeam system can be operated independently of specific beamlines. It can be transported easily and hence used for inter-institutional comparative studies. The quality of the minibeams allows us to perform in vitro and in vivo experiments in the future. The microDiamond was demonstrated to have great potential for online dosimetry for proton minibeams, yet requires more research to explain the observed discrepancies.

Tech Support

Section titled “Tech Support”

Original Source

Section titled “Original Source”

References

Section titled “References”
  1. 1912 - Roentgentiefentherapie mit metallnetzschutz
  2. 2023 - Spatially Fractionated, Microbeam and FLASH Radiation Therapy: A physics and multi-disciplinary approach [Crossref]
  3. 2022 - Should peak dose be used to prescribe spatially fractionated radiation therapy?—a review of preclinical studies [Crossref]
  4. 2020 - Spatially fractionated radiation therapy: History, present and the future [Crossref]
  5. 2020 - Animal models in microbeam radiation therapy: A scoping review [Crossref]
  6. 2022 - Technical aspects of proton minibeam radiation therapy: Minibeam generation and delivery [Crossref]
  7. 2016 - Proton minibeam radiation therapy reduces side effects in an in vivo mouse ear model [Crossref]
  8. 2019 - Spatially fractionated proton minibeams [Crossref]
  9. 2017 - Proton minibeam radiation therapy spares normal rat brain: Long-term clinical, radiological and histopathological analysis [Crossref]
  10. 2024 - Thoracic proton minibeam radiation therapy: Tissue preservation and survival advantage over conventional proton therapy [Crossref]

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