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Loading the tumor with ³¹P, ⁶³Cu and ⁸⁹Y provides an in vivo prompt gamma-based range verification for therapeutic protons

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FRONTIERS IN PHYSICS 2023年 11卷

作者： Cartechini, Giorgio Fogazzi, Elena Hart, Shanyn-Dee Pellegri, Luna Vanstalle, Marie Marafini, Michela La Tessa, Chiara Univ Trento Dept Phys Trento Italy Ist Nazl Fis Nucl TIFPA INFN Trento Inst Fundamental Phys & Applicat Trento Italy Univ Miami Dept Radiat Oncol Miami FL 33146 USA iThemba Lab Accelerator Based Sci Separated Sect Cyclotron Lab Somerset West South Africa Univ Witwatersrand Sch Phys Johannesburg South Africa Univ Strasbourg Inst Pluridisciplinaire Hubert Curien IPHC Ctr Natl Rech Sci CNRS Strasbourg France Museo Stor Fis & Ctr Studi & Ric Enr Fermi Rome Italy Ist Nazl Fis Nucl INFN Sect Roma 1 Rome Italy

Introduction: The main rationale for using protons in cancer treatment is based on the highly conformal dose distribution and normal tissue spearing compared to conventional radiotherapy. The main limit of proton therapy is the particle range uncertainty due to patient setup, dose calculation and imaging. To account for this, a safety margin is added to the tumor to ensure the prescribed dose to the target. Reducing range uncertainties would result in the reduction of irradiation volume and would allow full exploitation of the proton therapy benefits. In this work, we presented a feasibility study for a strategy to achieve in vivo proton range verification based on prompt gammas (PG). This approach relies on the detection of signature prompt gammas, generated by the interaction of primary protons with a non-radioactive element, that is selectively loaded into a tumor with a drug carrier. The number of characteristic gammas is directly related to the proton range, and its measurement provides an estimate of the position at which the primary beam stops with respect to the tumor location. Method: We identified the criteria for selecting potential candidate materials and combined them with TALYS predictions to make the selection. We carried out an experimental campaign to characterize the PG spectra generated by the chosen materials when irradiated with therapeutic protons and compared them with TOPAS Monte Carlo toolkit predictions. Results: We identified 31-Phosphorous, 63-Copper and 89-Yttrium as potential candidates for this application based on TALYS calculations. The experimental data confirmed that all candidates emit signature prompt gammas different from water (here used as a proxy for normal tissue), and that the gamma yield is directly proportional to the element concentration in the solution. Four specific gamma lines were detected for both P-31 (1.14, 1.26, 1.78, and 2.23 MeV) and Cu-63 (0.96, 1.17, 1.24, 1.326 MeV), while only one for Y-89 (1.06 MeV). The

关键词： proton therapy proton range verification prompt gamma TOPAS Monte Carlo 31-Phosporous 63-Copper 89-Yttrium

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Passive Ultrasound Localization Microscopy of Nanodroplet Vaporizations During proton Irradiation

IEEE OPEN JOURNAL OF ULTRASONICS, FERROELECTRICS, AND FREQUE...

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IEEE OPEN JOURNAL OF ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2022年 2卷 203-219页

作者： Heymans, Sophie V. Collado-Lara, Gonzalo Rovituso, Marta Vos, Hendrik J. D'Hooge, Jan De Jong, Nico Van den Abeele, Koen Katholieke Univ Leuven Dept Phys B-8500 Kortrijk Belgium Erasmus MC Univ Med Ctr Dept Cardiol Biomed Engn Grp NL-3015 CN Rotterdam Netherlands Katholieke Univ Leuven Dept Cardiovasc Sci B-3000 Leuven Belgium Holland Proton Therapy Ctr NL-2629 JH Delft Netherlands

Superheated nanodroplets (NDs) were recently proposed for in vivo proton range verification, owing to their ability to vaporize into echogenic microbubbles (MBs) upon exposure to ionizing radiation. In a previous publication, vaporization events were detected with 2D Ultrasound Localization Microscopy (ULM) based on a pulse-echo method. Here, we introduce P-ULM, a passive version of ULM, based on the detection of acoustic signatures emitted by vaporizing NDs, without actively transmitting ultrasound. Due to the lack of a time reference for the trigger of the ND vaporization, the time differences of arrival to each transducer element are used to retrieve the position of vaporizing NDs. P-ULM, compared to ULM, can continuously detect and super-localize sparse radiation-induced vaporization events with inherent specificity against already existing microbubbles, which otherwise would hinder range verification in the presence of vascular flow. We evaluated the localization performances of both methods theoretically and experimentally, by interleaving active and passive acquisitions on ND-phantoms irradiated with protons. P-ULM offered a higher sensitivity to vaporizations, as it detected twice as many events as ULM. Both methods retrieved, in the acoustic lateral direction, the proton range and range dispersion with sub-millimeter accuracy. In the acoustic axial direction, despite a degraded theoretical resolution limit, P-ULM retrieved the proton spot size with an accuracy similar to ULM. Importantly, P-ULM detected vaporization events with high specificity in the presence of flowing MBs, which makes the technique a candidate for in vivo proton range verification in the presence of flow.

关键词： Passive source localization ultrasound localization microscopy resolution limits nanodroplets phase change contrast agents proton range verification

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Optimization of the backing material of a low frequency PVDF detector for ion beam monitoring during small animal proton irradiation

Optimization of the backing material of a low frequency PVDF...

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IEEE International Ultrasonics Symposium (IEEE IUS)

作者： Lascaud, Julie Kowalewski, Rafal Wollant, Benjamin Carmigniani, Henri Schnuerle, Katrin Dash, Pratik Wieser, Hans-Peter Bortfeldt, Jonathan Kalunga, Ronaldo Rouffaudt, Remi Gerardt, Anais Vidal, Marie Herault, Joel Certon, Dominique Parodi, Katia Ludwig Maximilians Univ Munchen Garching Germany Univ Tours INSA Ctr Val Loire CNRS GREMAN UMR 7347 F-37071 Tours 2 France Ctr Antoine Lacassagne Federat Claude Lalanne 227 Ave Lanterne Nice France

ISBN: (纸本)9780738112091

This study investigates the use of PVDF sensors for the detection of low pressure kHz thermoacoustic signals, emanating from pulsed proton beams during small animal irradiation. In particular, the impact of the backing material and detector geometry on the measured signal amplitude and accuracy of time-of-flight estimations is assessed. A simulation model, including FLUKA Monte Carlo simulations of the proton dose, pressure propagation using k-Wave, modeling the backing geometry and a Mason model of the PVDF electroacoustic response is proposed. Thereafter, suitable backing materials are investigated by varying the backing density, the speed of sound and the detector geometry. Tungsten is found to be a good candidate to improve the sensor sensitivity, while maintaining accurate localization of the maximum of the proton dose, i.e., Bragg peak localized with an error lower than 5 % for the considered scenarios. Tungsten backing as thin as 2.5 mm allows to improve the sensitivity of the detector by a factor 4 compared to 10 mm epoxy backing.

关键词： PVDF ionoacoustics thermoacoustics proton range verification

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Applicability of Capacitive Micromachined Ultrasonic Transducers for the detection of proton-induced thermoacoustic waves

Applicability of Capacitive Micromachined Ultrasonic Transdu...

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IEEE International Ultrasonics Symposium (IUS)

作者： Lascaud, Julie Kalunga, Ronaldo Lehrack, Sebastian Wieser, Hans-Peter Englbrecht, Franz Siegfried Wuerl, Matthias Assmann, Walter Savoia, Alessandro Stuart Parodi, Katia Ludwig Maximilians Univ Munchen Garching Germany Roma Tre Univ Dept Engn Rome Italy

ISBN: (纸本)9781728145969

This study investigates the application of broadband capacitive micromachined ultrasonic transducers (CMUT) to ionoacoustics (i.e., the thermoacoustic emissions induced by the energy deposition of ion beam) over a wide frequency range from hundreds of kHz to a few MHz. A water tank was irradiated by a 20 MeV pulsed proton beam. The frequency and amplitude of the ionoacoustic waves were modulated by adding material before to penetrate into the water tank to change the beam energy and its spatial dimensions. The measurements were performed with a 12 MHz CMUT prototype and compared to ones obtained from a commercial 3.5 MHz piezoeletric transducer as well as to in silico studies employing the k-Wave Matlab toolbox in combination with FLUKA Monte Carlo simulations to derive the dose (i.e., energy deposition per mass) and initial pressure distribution. Comparison of the experimental and in silico results show that the CMUT bandwidth is wide enough to measure the signal without any degradation or attenuation of the frequency content in the investigated frequency range, thus ensuring accurate reconstruction of the dose distribution and potential bi-modality system for the co-registration of ionoacoustic and ultrasound imaging.

关键词： CMUT ionoacoustics proton range verification

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Reconstructing 3D proton dose distribution using ionoacoustics

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PHYSICS IN MEDICINE AND BIOLOGY 2019年第22期64卷 225005-225005页

作者： van Dongen, K. W. A. de Blecourt, J. Lens, E. Schaart, D. R. Vos, F. M. Delft Univ Technol Fac Appl Sci Dept Imaging Phys Delft Netherlands Delft Univ Technol Fac Appl Sci Dept Radiat Sci & Technol Delft Netherlands

In proton therapy high energy protons are used to irradiate a tumor. Ideally, the delivered proton dose distribution is measured during treatment to ensure patient safety and treatment effectiveness. Here we investigate if we can use the ionoacoustic wave field to monitor the actual proton dose distribution for the two most commonly used proton accelerators;the isochronous cyclotron and the synchrocyclotron. To this end we model the acoustic field generated by the protons when irradiating a heterogeneous cancerous breast with a 89 MeV proton beam. To differentiate between the systems, idealized temporal micro-structures of the beams have been implemented. Results show that by employing model-based inversion we are able to reconstruct the 3D dose distributions from the simulated noisy pressure fields. Good results are obtained for both systems;the absolute error in the position of the maximum amplitude of the dose distribution is 5.0?mm for the isochronous cyclotron and 5.2?mm for the synchrocyclotron. In conclusion, this numerical study suggests that the ionoacoustic wave field may be used to monitor the proton dose distribution during breast cancer treatment.

关键词： 3D inversion Bragg peak proton range verification ionoacoustics

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Ionizing radiation-induced acoustics for radiotherapy and diagnostic radiology applications

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MEDICAL PHYSICS 2018年第7期45卷 E707-E721页

作者： Hickling, Susannah Xiang, Liangzhong Jones, Kevin C. Parodi, Katia Assmann, Walter Avery, Stephen Hobson, Maritza El Naqa, Issam McGill Univ Dept Phys 1001 Boul Decarie Montreal PQ H4A 3J1 Canada McGill Univ Med Phys Unit 1001 Boul Decarie Montreal PQ H4A 3J1 Canada Univ Oklahoma Sch Elect & Comp Engn Norman OK 73019 USA Rush Univ Dept Radiat Oncol Med Ctr Chicago IL 60612 USA Ludwig Maximilians Univ Munchen Dept Med Phys D-85748 Garching Germany Univ Penn Dept Radiat Oncol Philadelphia PA 19104 USA McGill Univ Med Phys Unit Ctr Hlth Montreal H4A 3J1 PQ Canada McGill Univ Dept Phys Dept Oncol Montreal H4A 3J1 PQ Canada Univ Michigan Dept Radiat Oncol Ann Arbor MI 48103 USA

Acoustic waves are induced via the thermoacoustic effect in objects exposed to a pulsed beam of ionizing radiation. This phenomenon has interesting potential applications in both radiotherapy dosimetry and treatment guidance as well as low-dose radiological imaging. After initial work in the field in the 1980s and early 1990s, little research was done until 2013 when interest was rejuvenated, spurred on by technological advances in ultrasound transducers and the increasing complexity of radiotherapy delivery systems. Since then, many studies have been conducted and published applying ionizing radiation-induced acoustic principles into three primary research areas: Linear accelerator photon beam dosimetry, proton therapy range verification, and radiological imaging. This review article introduces the theoretical background behind ionizing radiation-induced acoustic waves, summarizes recent advances in the field, and provides an outlook on how the detection of ionizing radiation-induced acoustic waves can be used for relative and invivo dosimetry in photon therapy, localization of the Bragg peak in proton therapy, and as a low-dose medical imaging modality. Future prospects and challenges for the clinical implementation of these techniques are discussed.

关键词： low-dose imaging photon beam dosimetry proton range verification radiation acoustics thermoacoustic effect

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Sensitivity study of prompt gamma imaging of scanned beam proton therapy in heterogeneous anatomies

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RADIOTHERAPY AND ONCOLOGY 2016年第3期118卷 562-567页

作者： Janssens, Guillaume Smeets, Julien Stappen, Francois Vander Prieels, Damien Clementel, Enrico Hotoiu, Eugen-Lucian Sterpin, Edmond Ion Beam Applicat SA Ottignies Belgium Catholic Univ Louvain ICTEAM Inst iMagX Project Louvain La Neuve Belgium Catholic Univ Louvain Ctr Mol Imaging Radiotherapy & Oncol Inst Rech Expt & Clin B-1200 Brussels Belgium

Background and purpose: To investigate the use of a fast analytical prediction algorithm in the evaluation of the accuracy in Bragg peak position estimation using prompt gamma imaging in realistic anatomies. Material and methods: Brain, nasal cavity and lung spot scanning treatments were planned on an anthropomorphic phantom. Plan delivery in a clinical proton therapy facility was monitored using a prompt gamma camera. A pencil-beam algorithm was developed to simulate prompt gamma acquisition. For each spot, the sensitivity to setup and CT conversion errors was evaluated based on error scenarios. Results: Good agreement was found between simulations and measurements (average shift of 0.4 mm on whole-layer profiles). The spots with greatest sensitivity to setup or CT conversion errors could be identified. The comparison between expected and estimated shifts showed that the errors in shift estimation due to heterogeneities were in average lower than 1 mm in all cases except the lung. In the lung case, only 40% of the spots showed accuracy better than 2 mm. Conclusions: The analytical prediction algorithm was successfully used to simulate prompt gamma acquisitions of scanned treatment plans. The accuracy in Bragg peak position estimation was generally sub millimeter in heterogeneous anatomies, except in lung tissues. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

关键词： proton range verification Prompt gamma imaging range uncertainties

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How proton pulse characteristics influence protoacoustic determination of proton-beam range: simulation studies

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PHYSICS IN MEDICINE AND BIOLOGY 2016年第6期61卷 2213-2242页

作者： Jones, Kevin C. Seghal, Chandra M. Avery, Stephen Univ Penn Dept Radiat Oncol Philadelphia PA 19104 USA Univ Penn Dept Radiol Philadelphia PA 19104 USA

The unique dose deposition of proton beams generates a distinctive thermoacoustic (protoacoustic) signal, which can be used to calculate the proton range. To identify the expected protoacoustic amplitude, frequency, and arrival time for different proton pulse characteristics encountered at hospital-based proton sources, the protoacoustic pressure emissions generated by 150 MeV, pencil-beam proton pulses were simulated in a homogeneous water medium. proton pulses with Gaussian widths ranging up to 200 mu s were considered. The protoacoustic amplitude, frequency, and time-of-flight (TOF) range accuracy were assessed. For TOF calculations, the acoustic pulse arrival time was determined based on multiple features of the wave. Based on the simulations, Gaussian proton pulses can be categorized as Dirac-delta-function-like (FWHM < 4 mu s) and longer. For the delta-function-like irradiation, the protoacoustic spectrum peaks at 44.5 kHz and the systematic error in determining the Bragg peak range is <2.6 mm. For longer proton pulses, the spectrum shifts to lower frequencies, and the range calculation systematic error increases (<= 23 mm for FWHM of 56 mu s). By mapping the protoacoustic peak arrival time to range with simulations, the residual error can be reduced. Using a proton pulse with FWHM = 2 mu s results in a maximum signal-to-noise ratio per total dose. Simulations predict that a 300 nA, 150 MeV, FWHM = 4 mu s Gaussian proton pulse (8.0 x 10(6) protons, 3.1 cGy dose at the Bragg peak) will generate a 146 mPa pressure wave at 5 cm beyond the Bragg peak. There is an angle dependent systematic error in the protoacoustic TOF range calculations. Placing detectors along the proton beam axis and beyond the Bragg peak minimizes this error. For clinical proton beams, protoacoustic detectors should be sensitive to <400 kHz (for -20 dB). Hospital-based synchrocyclotrons and cyclotrons are promising sources of proton pulses for generating clinically measurable protoacoustic em

关键词： proton range verification proton-acoustics protoacoustics radiation therapy pulsed proton beam acoustic pulses ionoacoustics

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Measurement of Acoustic Emissions Generated by a Pulsed proton Beam from a Hospital-Based Clinical Cyclotron

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RADIOTHERAPY AND ONCOLOGY 2016年 118卷 S55-S56页

作者： Jones, K. C. Vander Stappen, F. Bawiec, C. R. Janssens, G. Lewin, P. A. Prieels, D. Solberg, T. D. Sehgal, C. M. Avery, S. Univ Penn Dept Radiat Oncol Philadelphia PA 19104 USA Ion Beam Applicat SA Louvain La Neuve Belgium Drexel Univ Sch Biomed Engn Philadelphia PA 19104 USA Univ Penn Dept Radiol Philadelphia PA 19104 USA

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Commissioning of a Compton camera for ion beam range verification via prompt γ detection using low-energy and clinical particle beams

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RADIOTHERAPY AND ONCOLOGY 2016年 118卷 S2-S3页

作者： Aldawood, S. Bortfeldt, J. Boehmer, M. Castelhano, I. Dedes, G. Enghardt, W. Fiedler, F. Gernhaeuser, R. Golnik, C. Helmbrecht, S. Hueso-Gonzalez, F. Von der Kolff, H. Kormoll, T. Lang, C. Liprandi, S. Lutter, R. Maier, L. Marinsek, T. Pausch, G. Petzoldt, J. Pocevicius, M. Roemer, K. Lozano, I. Valencia Schaart, D. R. Parodi, K. Thirolf, P. G. Ludwig Maximilians Univ Munchen Fac Phys Dept Med Phys Munich Germany King Saud Univ Dept Phys & Astron Riyadh Saudi Arabia Tech Univ Munich Phys Dept E12 Garching Germany Univ Lisbon Fac Sci Lisbon Portugal Natl Ctr Radiat Res Oncol OncoRay Dresden Germany Helmholtz Zentrum Dresden Rossendorf Radiat Phys Div Dresden Germany Helmholtz Zentrum Dresden Rossendorf Inst Radiooncol Dresden Germany Delft Univ Technol Fac Appl Sci Radiat Sci & Technol Delft Netherlands

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