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Title: Micrometer-resolved film dosimetry using a microscope in microbeam radiation therapy

Abstract

Purpose: Microbeam radiation therapy (MRT) is a still preclinical tumor therapy approach that uses arrays of a few tens of micrometer wide parallel beams separated by a few 100 μm. The production, measurement, and planning of such radiation fields are a challenge up to now. Here, the authors investigate the feasibility of radiochromic film dosimetry in combination with a microscopic readout as a tool to validate peak and valley doses in MRT, which is an important requirement for a future clinical application of the therapy. Methods: Gafchromic{sup ®} HD-810 and HD-V2 films are exposed to MRT fields at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF) and are afterward scanned with a microscope. The measured dose is compared with Monte Carlo calculations. Image analysis tools and film handling protocols are developed that allow accurate and reproducible dosimetry. The performance of HD-810 and HD-V2 films is compared and a detailed analysis of the resolution, noise, and energy dependence is carried out. Measurement uncertainties are identified and analyzed. Results: The dose was measured with a resolution of 5 × 1000 μm{sup 2} and an accuracy of 5% in the peak and between 10% and 15% in the valley region.more » As main causes for dosimetry uncertainties, statistical noise, film inhomogeneities, and calibration errors were identified. Calibration errors strongly increase at low doses and exceeded 3% for doses below 50 and 70 Gy for HD-V2 and HD-810 films, respectively. While the grain size of both film types is approximately 2 μm, the statistical noise in HD-V2 is much higher than in HD-810 films. However, HD-810 films show a higher energy dependence at low photon energies. Conclusions: Both film types are appropriate for dosimetry in MRT and the microscope is superior to the microdensitometer used before at the ESRF with respect to resolution and reproducibility. However, a very careful analysis of the image data is required. Dosimetry at low photon energies should be performed with great caution due to the energy sensitivity of the films. In this respect, HD-V2 films showed to have an advantage over HD-810 films. However, HD-810 films have a lower statistical noise level. When a higher resolution is required, e.g., for the dosimetry of pencil beam irradiations, noise may render HD-V2 films inapplicable.« less

Authors:
;  [1]; ;  [2];  [3]
  1. The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG (United Kingdom)
  2. Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)
  3. European Synchrotron Radiation Facility, 6 rue Jules Horowitz, Grenoble Cedex 9 38043 (France)
Publication Date:
OSTI Identifier:
22413620
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 42; Journal Issue: 7; Other Information: (c) 2015 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND TECHNOLOGY; 60 APPLIED LIFE SCIENCES; CALIBRATION; ENERGY DEPENDENCE; ERRORS; EUROPEAN SYNCHROTRON RADIATION FACILITY; FILM DOSIMETRY; IMAGE PROCESSING; MICROSCOPES; MONTE CARLO METHOD; NEOPLASMS; NOISE; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Bartzsch, Stefan, E-mail: stefan.bartzsch@icr.ac.uk, Oelfke, Uwe, Lott, Johanna, Welsch, Katrin, and Bräuer-Krisch, Elke. Micrometer-resolved film dosimetry using a microscope in microbeam radiation therapy. United States: N. p., 2015. Web. doi:10.1118/1.4922001.
Bartzsch, Stefan, E-mail: stefan.bartzsch@icr.ac.uk, Oelfke, Uwe, Lott, Johanna, Welsch, Katrin, & Bräuer-Krisch, Elke. Micrometer-resolved film dosimetry using a microscope in microbeam radiation therapy. United States. doi:10.1118/1.4922001.
Bartzsch, Stefan, E-mail: stefan.bartzsch@icr.ac.uk, Oelfke, Uwe, Lott, Johanna, Welsch, Katrin, and Bräuer-Krisch, Elke. Wed . "Micrometer-resolved film dosimetry using a microscope in microbeam radiation therapy". United States. doi:10.1118/1.4922001.
@article{osti_22413620,
title = {Micrometer-resolved film dosimetry using a microscope in microbeam radiation therapy},
author = {Bartzsch, Stefan, E-mail: stefan.bartzsch@icr.ac.uk and Oelfke, Uwe and Lott, Johanna and Welsch, Katrin and Bräuer-Krisch, Elke},
abstractNote = {Purpose: Microbeam radiation therapy (MRT) is a still preclinical tumor therapy approach that uses arrays of a few tens of micrometer wide parallel beams separated by a few 100 μm. The production, measurement, and planning of such radiation fields are a challenge up to now. Here, the authors investigate the feasibility of radiochromic film dosimetry in combination with a microscopic readout as a tool to validate peak and valley doses in MRT, which is an important requirement for a future clinical application of the therapy. Methods: Gafchromic{sup ®} HD-810 and HD-V2 films are exposed to MRT fields at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF) and are afterward scanned with a microscope. The measured dose is compared with Monte Carlo calculations. Image analysis tools and film handling protocols are developed that allow accurate and reproducible dosimetry. The performance of HD-810 and HD-V2 films is compared and a detailed analysis of the resolution, noise, and energy dependence is carried out. Measurement uncertainties are identified and analyzed. Results: The dose was measured with a resolution of 5 × 1000 μm{sup 2} and an accuracy of 5% in the peak and between 10% and 15% in the valley region. As main causes for dosimetry uncertainties, statistical noise, film inhomogeneities, and calibration errors were identified. Calibration errors strongly increase at low doses and exceeded 3% for doses below 50 and 70 Gy for HD-V2 and HD-810 films, respectively. While the grain size of both film types is approximately 2 μm, the statistical noise in HD-V2 is much higher than in HD-810 films. However, HD-810 films show a higher energy dependence at low photon energies. Conclusions: Both film types are appropriate for dosimetry in MRT and the microscope is superior to the microdensitometer used before at the ESRF with respect to resolution and reproducibility. However, a very careful analysis of the image data is required. Dosimetry at low photon energies should be performed with great caution due to the energy sensitivity of the films. In this respect, HD-V2 films showed to have an advantage over HD-810 films. However, HD-810 films have a lower statistical noise level. When a higher resolution is required, e.g., for the dosimetry of pencil beam irradiations, noise may render HD-V2 films inapplicable.},
doi = {10.1118/1.4922001},
journal = {Medical Physics},
number = 7,
volume = 42,
place = {United States},
year = {Wed Jul 15 00:00:00 EDT 2015},
month = {Wed Jul 15 00:00:00 EDT 2015}
}
  • The measurement of spatially resolved high doses in microbeam radiation therapy has always been a challenging task, where a combination of high dose response and high spatial resolution (microns) is required for synchrotron radiation peaked around 50 keV. The x-ray induced Sm{sup 3+}{yields} Sm{sup 2+} valence conversion in Sm{sup 3+} doped fluorophosphates glasses has been tested for use in x-ray dosimetry for microbeam radiation therapy. The conversion efficiency depends almost linearly on the dose of irradiation up to {approx}5 Gy and saturates at doses exceeding {approx}80 Gy. The conversion shows strong correlation with x-ray induced absorbance of the glass whichmore » is related to the formation of phosphorus-oxygen hole centers. When irradiated through a microslit collimator, a good spatial resolution and high ''peak-to-valley'' contrast have been observed by means of confocal photoluminescence microscopy.« less
  • Purpose: The feasibility of MRT has recently been demonstrated utilizing a new technology of Carbon-Nano-Tube(CNT) field emission x-ray sources.This approach can deliver very high dose(10's of Gy) in narrow stripes(sub-mm) of radiation which enables the study of novel radiation treatment approaches. Here we investigate the application of highresolution (50um isotropic) PRESAGE/Optical-CT 3D dosimetry techniques to characterize the radiation delivered in this extremely dosimetrically challenging scenario. Methods: The CNT field emission x-ray source irradiator comprises of a linear cathode array and a novel collimator alignment system. This allows a precise delivery of high-energy small beams up to 160 kVp. A cylindricalmore » dosimeter (∼2.2cm in height ∼2.5cm in diameter) was irradiated by CNT MRT delivering 3 strips of radiation with a nominal entrance dose of 32 Gy.A second dosimeter was irradiated with similar entrance dose, with a regular x-ray irradiator collimated to microscopical strip-beams. 50um (isotropic) 3D dosimetry was performed using an in-house optical-CT system designed and optimized for high resolution imaging (including a stray light deconvolution correction).The percentage depth dose (PDD), peak-to-valley ratio (PVR) and beam width (FWHM) data were obtained and analyzed in both cases. Results: High resolution 3D images were successfully achieved with the prototype system, enabling extraction of PDD and dose profiles. The PDDs for the CNT irradiation showed pronounced attenuation, but less build-up effect than that from the multibeam irradiation. The beam spacing between the three strips has an average value of 0.9mm while that for the 13 strips is 1.5 mm at a depth of 16.5 mm. The stray light corrected image shows line profiles with reduced noise and consistent PVR values. Conclusion: MRT dosimetry is extremely challenging due to the ultra small fields involved.This preliminary application of a novel, ultra-high resolution, optical-CT 3D dosimetry system shows promise, but further work is required to validate and investigate accuracy and artifacts. This work was supported by NIH R01CA100835.« less
  • The tissue-sparing effect of parallel, thin (narrower than 100em) synchrotron-generated X-ray planar beams (microbeams) in healthy tissues including the central nervous system (CNS) is known since early 1990s. This, together with a remarkable preferential tumoricidal effect of such beam arrays observed at high doses, has been the basis for labeling the method microbeam radiation therapy (MRT). Recent studies showed that beams as thick as 0.68mm ('thick microbeams') retain part of their sparing effect in the rat's CNS, and that two such orthogonal microbeams arrays can be interlaced to produce an unsegmented field at the target, thus producing focal targeting. Wemore » measured the half-value layer (HVL) of our 120-keV median-energy beam in water phantoms, and we irradiated stereotactically bis acrylamide nitrogen gelatin (BANG)-gel-filled phantoms, including one containing a human skull, with interlaced microbeams and imaged them with MRI. A 43-mm water HVL resulted, together with an adequately large peak-to-valley ratio of the microbeams' three-dimensional dose distribution in the vicinity of the 20mmx20mmx20mm target deep into the skull. Furthermore, the 80-20% dose falloff was a fraction of a millimeter as predicted by Monte Carlo simulations. We conclude that clinical MRT will benefit from the use of higher beam energies than those used here, although the current energy could serve certain neurosurgical applications. Furthermore, thick microbeams particularly when interlaced present some advantages over thin microbeams in that they allow the use of higher beam energies and they could conceivably be implemented with high power orthovoltage X-ray tubes.« less
  • Purpose: Microbeam Radiation Therapy (MRT) is an experimental radiation therapy that has demonstrated a higher therapeutic ratio than conventional radiation therapy in animal studies. There are several roadblocks in translating the promising treatment technology to clinical application, one of which is the lack of a real-time, high-resolution dosimeter. Current clinical radiation detectors have poor spatial resolution and, as such, are unsuitable for measuring microbeams with submillimeter-scale widths. Although GafChromic film has high spatial resolution, it lacks the real-time dosimetry capability necessary for MRT preclinical research and potential clinical use. In this work we have demonstrated the feasibility of using amore » nanoscintillator fiber-optic detector (nanoFOD) system for real-time MRT dosimetry. Methods: A microplanar beam array is generated using a x-ray research irradiator and a custom-made, microbeam-forming collimator. The newest generation nanoFOD has an effective size of 70 µm in the measurement direction and was calibrated against a kV ion chamber (RadCal Accu-Pro) in open field geometry. We have written a computer script that performs automatic data collection with immediate background subtraction. A computer-controlled detector positioning stage is used to precisely measure the microbeam peak dose and beam profile by translating the stage during data collection. We test the new generation nanoFOD system, with increased active scintillation volume, against the previous generation system. Both raw and processed data are time-stamped and recorded to enable future post-processing. Results: The real-time microbeam dosimetry system worked as expected. The new generation dosimeter has approximately double the active volume compared to the previous generation resulting in over 900% increase in signal. The active volume of the dosimeter still provided the spatial resolution that meets the Nyquist criterion for our microbeam widths. Conclusion: We have demonstrated that real-time dosimetry of MRT microbeams is feasible using a nanoscintillator fiber-optic detector with integrated positioning system.« less
  • Purpose: Microbeam radiation therapy (MRT) is defined as the use of parallel, microplanar x-ray beams with an energy spectrum between 50 and 300 keV for cancer treatment and brain radiosurgery. Up until now, the possibilities of MRT have mainly been studied using synchrotron sources due to their high flux (100s Gy/s) and approximately parallel x-ray paths. The authors have proposed a compact x-ray based MRT system capable of delivering MRT dose distributions at a high dose rate. This system would employ carbon nanotube (CNT) field emission technology to create an x-ray source array that surrounds the target of irradiation. Usingmore » such a geometry, multiple collimators would shape the irradiation from this array into multiple microbeams that would then overlap or interlace in the target region. This pilot study demonstrates the feasibility of attaining a high dose rate and parallel microbeam beams using such a system. Methods: The microbeam dose distribution was generated by our CNT micro-CT scanner (100μm focal spot) and a custom-made microbeam collimator. An alignment assembly was fabricated and attached to the scanner in order to collimate and superimpose beams coming from different gantry positions. The MRT dose distribution was measured using two orthogonal radiochromic films embedded inside a cylindrical phantom. This target was irradiated with microbeams incident from 44 different gantry angles to simulate an array of x-ray sources as in the proposed compact CNT-based MRT system. Finally, phantom translation in a direction perpendicular to the microplanar beams was used to simulate the use of multiple parallel microbeams. Results: Microbeams delivered from 44 gantry angles were superimposed to form a single microbeam dose distribution in the phantom with a FWHM of 300μm (calculated value was 290 μm). Also, during the multiple beam simulation, a peak to valley dose ratio of ∼10 was found when the phantom translation distance was roughly 4x the beam width. The first prototype CNT-based x-ray tube dedicated to the development of compact MRT technology development was proposed and planned based on the preliminary experimental results presented here and the previous corresponding Monte Carlo simulations. Conclusions: The authors have demonstrated the feasibility of creating microbeam dose distributions at a high dose rate using a proposed compact MRT system. The flexibility of CNT field emission x-ray sources could possibly bring compact and low cost MRT devices to the larger research community and assist in the translational research of this promising new approach to radiation therapy.« less