An image-guided precision proton radiation platform for preclinical<i>in vivo</i>research

Ford, Eric; Emery, Robert; Huff, Daniel T; Narayanan, Manoj; Schwartz, Jeffrey L.; Cao, Ning; Meyer, Juergen; Rengan, Ramesh; Zeng, Jing; Sandison, George A.; Laramore, George E.; Mayr, Nina A.

doi:10.1088/1361-6560/62/1/43

Cited by 38 publications

(51 citation statements)

References 71 publications

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“…With a 24‐MeV proton beam, tumors as small as 0.5 mm can be irradiated with a flat SOBP. This was also demonstrated by Ford et al . who compared the simulated Bragg peak obtained with a 30‐MeV proton beam with a 100 MeV modulated beam.…”

Section: Discussionsupporting

confidence: 58%

“…These three examples represent typical tumor sizes in mice . The proton beam energies are chosen in agreement with existing facilities that can deliver energies compatible with small‐animal irradiation . For each tested tumor configuration, the energy straggling of the beam is fixed at σ E = 150 keV (typical value for 25 MeV cyclotron), with a dose D p = 1 Gy delivered to the tumor volume.…”

Section: Methodsmentioning

confidence: 99%

“…For instance, in mice, a lung tumor measures less than 1.0 mm, and a brain tumor between 2.0 and 4.0 mm, which requires accurate dose calculations with a spatial submillimeter resolution . To achieve high positioning accuracy (<0.025 mm) and spatial resolution (<0.145 mm for mice) when irradiating small‐size animal tumors, image‐guided irradiation platforms have been developed, both for conventional photon radiotherapy and proton therapy . These platforms led to the development of dedicated tools, including adapted treatment planning systems (TPS) for small‐animal irradiation.…”

Section: Introductionmentioning

confidence: 99%

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Analytical dose modeling for preclinical proton irradiation of millimetric targets

et al. 2017

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Purpose: Due to the considerable development of proton radiotherapy, several proton platforms have emerged to irradiate small animals in order to study the biological effectiveness of proton radiation. A dedicated analytical treatment planning tool was developed in this study to accurately calculate the delivered dose given the specific constraints imposed by the small dimensions of the irradiated areas. Methods: The treatment planning system (TPS) developed in this study is based on an analytical formulation of the Bragg peak and uses experimental range values of protons. The method was validated after comparison with experimental data from the literature and then compared to Monte Carlo simulations conducted using GEANT4. Three examples of treatment planning, performed with phantoms made of water targets and bone-slab insert, were generated with the analytical formulation and GEANT4. Each treatment planning was evaluated using dose-volume histograms and gamma index maps. Results: We demonstrate the value of the analytical function for mouse irradiation, which requires a targeting accuracy of 0.1 mm. Using the appropriate database, the analytical modeling limits the errors caused by misestimating the stopping power. For example, 99% of a 1-mm tumor irradiated with a 24-MeV beam receives the prescribed dose. The analytical dose deviations from the prescribed dose remain within the dose tolerances stated by report 62 of the International Commission on Radiation Units and Measurements for all tested configurations. In addition, the gamma index maps show that the highly constrained targeting accuracy of 0.1 mm for mouse irradiation leads to a significant disagreement between GEANT4 and the reference. This simulated treatment planning is nevertheless compatible with a targeting accuracy exceeding 0.2 mm, corresponding to rat and rabbit irradiations. Conclusion: Good dose accuracy for millimetric tumors is achieved with the analytical calculation used in this work. These volume sizes are typical in mouse models for radiation studies. Our results demonstrate that the choice of analytical rather than simulated treatment planning depends on the animal model under consideration.

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Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analytical dose modeling for preclinical proton irradiation of millimetric targets

et al. 2017

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“…15 Currently, proton preclinical platforms (E ≤ 50 MeV) are burgeoning, offering the technical precision required to deliver precise millimeter-sized beams to localized regions within rodents. [16][17][18] Small-animal radiotherapy research platforms mimicking accurately human radiotherapy conditions are needed to reproduce pathologies observed in patients (improvement of animal models) and better understand the therapeutic possibilities and toxicities of PT. Several studies already improved the beam delivery and dose calculation for focal irradiation in the rat brain with gamma rays 19 and image-guided x rays.…”

Section: Introductionmentioning

confidence: 99%

Dosimetry and characterization of a 25‐MeV proton beam line for preclinical radiobiology research

et al. 2019

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Purpose With the increase in proton therapy centers, there is a growing need to make progress in preclinical proton radiation biology to give accessible data to medical physicists and practicing radiation oncologists. Methods A cyclotron usually producing radioisotopes with a proton beam at an energy of about 25 MeV after acceleration, was used for radiobiology studies. Depleted silicon surface barrier detectors were used for the beam energy measurement. A complementary metal oxide semiconductor (CMOS) sensor and a plastic scintillator detector were used for fluence measurement, and compared to Geant4 and an in‐house analytical dose modeling developed for this purpose. Also, from the energy measurement of each attenuated beam, the dose‐averaged linear energy transfer (LETd) was calculated with Geant4. Results The measured proton beam energy was 24.85 ± 0.14 MeV with an energy straggling of 127 ± 22 keV before scattering and extraction in air. The measured flatness was within ± 2.1% over 9 mm in diameter. A wide range of LETd is achievable: constant between the entrance and the exit of the cancer cell sample ranging from 2.2 to 8 keV/μm, beyond 20 keV/μm, and an average of 2–5 keV/μm in a scattering spread‐out Bragg peak calculated for an example of a 6‐mm‐thick xenograft tumor. Conclusion The dosimetry and the characterization of a 25‐MeV proton beam line for preclinical radiobiology research was performed by measurements and modeling, demonstrating the feasibility of delivering a proton beam for preclinical in vivo and in vitro studies with LETd of clinical interest.

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“…The preclinical proton beams not using clinical proton therapy accelerators constitute of either modified Van de Graaff accelerators, 3,4 singletron accelerators, 5 or radioisotope production cyclotrons. [6][7][8][9][10] Even if trying to achieve conventional dose rates of 3-5 cGy/s or dose rates larger than 40 Gy/s for flash irradiation, the main obstacle to overcome on a medical cyclotron is to reduce the proton beam current. 11 Proton beam currents during radioisotope productions can range up to 150 µA.…”

Section: Introductionmentioning

confidence: 99%

Design and verification of an external radiobiological beam port on a 16.5 MeV GE PETtrace proton cyclotron

et al. 2019

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Purpose Protons and heavy ions are considered to be ideal particles for use in external beam radiotherapy due to the superior properties of the dose distribution. While a photon (x‐ray) beam delivers considerable dose to healthy tissues around the tumor, a proton beam that is delivered with sufficient energies has: a low entrance dose (the dose in front of the tumor); a high‐dose region within the tumor, known as the Bragg peak; and, no exit dose beyond the tumor. Proton therapy is the next major step in advancing radiotherapy treatment. The purpose of this project was to adapt an existing radioisotope production cyclotron, a General Electric (GE) PETtrace, to enable radiobiological studies using proton beams. During routine use the PETtrace delivers 16.5 MeV protons to target with beam currents in the range of 10–100 µA resulting in dose rates in the order of kGy/s. To achieve the aim of the project the dose rate had to be reduced to the Gy/min range, without attenuating the proton energy below 5 MeV. This paper covers the design, construction and validation of the beam port. Methods Monte Carlo simulations were performed, using GEANT4, SRIM and PACE4 to design the beam port and optimize its components. Once the beam port was fabricated, validation experiments were performed using EBT3 and HD‐V2 Gafchromic™ films, and a Keithley 6485 picoampere meter. Results and conclusion The external beam port was successfully modeled, designed and fabricated. By using a 0.25 mm thick gold foil and a brass pin‐hole collimator the beam was spread from a narrow full beam diameter of 10 mm to a wide beam with a 5% flatness area in the center of the beam that had a diameter of ~20 mm. In using this system the dose rate was reduced from kGy/s to ~30 Gy/min.

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An image-guided precision proton radiation platform for preclinicalin vivoresearch

Cited by 38 publications

References 71 publications

Analytical dose modeling for preclinical proton irradiation of millimetric targets

Analytical dose modeling for preclinical proton irradiation of millimetric targets

Dosimetry and characterization of a 25‐MeV proton beam line for preclinical radiobiology research

Design and verification of an external radiobiological beam port on a 16.5 MeV GE PETtrace proton cyclotron

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