Loma Linda University

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Andrew Wroe, PhD
Professor, Radiation Medicine
School of Medicine
Publications    Scholarly Journals--Submitted
  • A. Teran, G. McAuley, J. M. Slater, J. D. Slater, A Wroe, Evaluation of the dosimetric properties of a diode detector to proton radiosurgery, Medical Physics, Submitted March 2014 ( 3/2014 )
  • K. Williams, R. Schulte, K. Schubert, A. Wroe, Evaluation of Mathematical Algorithms for Automatic Patient Alignment in Radiosurgery, Submitted to Technology in Cancer Research and Treatment February 2014. ( 2/2014 )
  • Nie Y, Chen Y, Hurley R, Bu S, Rhee K, Knect M, Plesiu G, Schneider J, Semotiuk A, Shihadeh F, Zubkov I, Koss P, McAuley G, Wroe A, Schubert K, Schulte R. An experimental system for focal irradiation of small animals with narrow proton beams: design and performance studies, Submitted to Physics in Medicine and Biology, 2013 ( 8/2013 )
  Scholarly Journals--Published
  • A. Wroe, D. Bush, R. Schulte, J. Slater, Clinical Immobilization Techniques in Proton Therapy, Technology in Cancer Research and Treatment, December 2013, DOI:10.7785/tcrt.2012.500398. ( 12/2013 )
  • D. Gridley, M. Pecaut, X. Mao, A. Wroe, X. Luo-Owen, Biological Effects of Passive Versus Active Scanning Proton Beams on Human Lung Epithelial Cells, Technology in Cancer Research and Treatment, December 2013, DOI:10.7785/tcrt.2012.500392. ( 12/2013 )
  • J. Sanzari, X. Wan, G. Krigsfeld, A. Wroe, D. Gridley, A. Kennedy, The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model, Gravitational and Space Biology, Volume 1, Number 1, pages 79-94, October 2013. ( 10/2013 )
  • A. Wroe, D. Bush, J. Slater, Immobilization Considerations in Proton Therapy, Technology in Cancer Research and Treatment, September 2013, DOI: 10.7785/tcrt.2012.500376. ( 9/2013 )
  • J. Sanzari, X. Wan, G. Krigsfeld, G. L. King, A. Miller, R. Mick, D. Gridley, A. Wroe, S. Rightnar, D. Dolney, A. Kennedy, Effects of Solar Particle Event Proton Radiation on Parameters Related to Ferret Emesis, Radiation Research, 180, 2, pages 166-176, 2013, DOI: 10.1667/RR3173.1. ( 7/2013 )
  • J. Sanzari, X. Wan, A. Wroe, S. Rightnar, K. Cengel, E. Diffenderfer, G. Krigsfeld, D. Gridley, A. Kennedy, Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model, Radiation Research, 180, 1, pages 7-16, 2013, DOI: 10.1667/RR3027.1. ( 5/2013 )
  • A. Wroe, A. Ghebremedhin, I. Gordon, R. Schulte, J. Slater, Water Equivalent Thickness Analysis of Immobilization Devices for Clinical Implementation in Proton Therapy, Technology in Cancer Research and Treatment, May 2013, DOI: 10.7785/tcrtexpress.2013.600260. ( 5/2013 )
  • G. Krigsfeld, A. Savage, J. Sanzari, A. Wroe, D. Gridley, A. Kennedy, Mechanism of hypocoagulability in proton-irradiated ferrets, International Journal of Radiobiology, May 2013, DOI:10.3109/09553002.2013.802394 ( 5/2013 )
  • A. J. Wroe, R. W. Schulte, S. Barnes, G. McAuley, J. D. Slater, J. M. Slater, Proton Beam Scattering System Optimization for Clinical and Research Applications, Medical Physics, Volume 40, Issue 4, 2013. ( 4/2013 )
  • S. Barnes, G. McAuley, J. M. Slater, A. J. Wroe, The effects of mapping CT images to Monte Carlo materials on GEANT4 proton simulation accuracy, Medical Physics, Volume 40, Issue 4, 2013. ( 4/2013 )
  • G. McAuley, S. Barnes, J. M. Slater, A. Wroe, Monte Carlo simulation of single-plane magnetically focused narrow proton beams, Physics in Medicine and Biology, Vol 58, pages 535-553, 2013. ( 1/2013 )
  • R. Schulte, A. Wroe, New Developments in Treatment Planning and Verification of Particle Beam Therapy, Translational Cancer Research, Vol. 1, No. 3, pages 184-195, 2012. ( 10/2012 )
  • R. F. Hurley, R.W. Schulte, V. A. Bashkirov, A. J. Wroe, A. Ghebremedhin, H. F.-W. Sadrozinski, V. Rykalin, G. Coutrakon, P. Koss, and B. Patyal, Water-equivalent path length calibration of a prototype proton CT scanner, Medical Physics, Volume 39, Issue 5, Pages 2438-2446, 2012. ( 5/2012 )
  • A.L. Ziebell, B. Clasie, A. Wroe, R.W. Schulte, M.I. Reinhard, S.J. Dowdell, M.L. Lerch, M. Petasecca, V.L. Perevertaylo, O.S. Zinets, I.E. Anokhin, and A.B. Rosenfeld, Solid state diode – Ionization chamber method for measuring out-of-field neutron dose in proton therapy, Radiation Measurements, Volume 46, Issue 12, pages 1638-1642, 2011 ( 12/2011 )
  • D. Gridley, T. Freeman, A. Makinde, A. Wroe, X. Luo-Owen, J. Tian, X. Mao, S. Rightnar, A. Kennedy, J. Slater, M. Pecaut, Comparison of proton and electron radiation effects on biological responses in liver, spleen and blood, International Journal of Radiation Biology, Vol 87, Issue 12, pp. 1173-1181, 2011. ( 11/2011 )
  • Dicello J. F., Gersey B. B., Gridley D. S., Coutrakon G. B., Lesyna D., Pisacane V. L., Robertson J. B., Schulte R. W., Slater J. D., Wroe A. J., and Slater J.M., Microdosimetric comparison of scanned and conventional proton beams used in radiation therapy, Radiat Prot Dosimetry. 143, 513-518, 2011 ( 6/2011 )
  • Casey J. Maks, X. Steven Wan, Jeffrey H. Ware, Ana L. Romero-Weaver, Jenine K. Sanzari, Jolaine M. Wilson, Steve Rightnar, Andrew J. Wroe, Peter Koss, Daila S. Gridley, James M. Slater and Ann R. Kennedy, Analysis of White Blood Cell Counts in Mice after Gamma- or Proton-Radiation Exposure, Radiation Research, Volume 176, Issue 2, 2011. ( 4/2011 )
  • D. Gridley, R. Grover, L. Loredo, A. Wroe, J. D. Slater, J. M. Slater, Proton-beam therapy for tumors of the CNS. Expert Review of Neurotherapeutics p319-330, 2010. ( 2/2010 )
  • Clasie B., Wroe A., Kooy H., Depauw N.,Flanz J., Paganetti, H., and Rosenfeld A., Experimental and theoretical assessment of out-of-field absorbed dose in proton fields. Medical Physics, Volume 37, Issue 1, pages 311-321, 2010 ( 1/2010 )
  • V. A. Bashkirov, R. W. Schulte, A. J. Wroe, H. Sadrozinski, E. Gargioni, B. Grosswendt, Experimental Validation of Track Structure Models, IEEE Transactions on Nuclear Science, Volume 56, Issue 5, pages 2859-2863, 2009 ( 10/2009 )
  • A. L. Ziebell, S. J. Dowdell, M. I. Reinhard, B. Clasie, A. Wroe, R. W. Schulte, M. L. Lerch, M. Petaseca, V. Perevertaylo, I. E. Anokhin, A. B. Rosenfeld, Dual detector system for measuring out-of-field neutron dose in proton therapy, IEEE Nuclear Science Symposium Conference Record, PP 2358-2361, 2009. ( 10/2009 )
  • A. Wroe, R. Schulte, A. Fazzi, A. Pola, S. Agosteo, A. Rosenfeld, RBE estimation of proton radiation fields using a DE-E telescope, Medical Physics, Volume 36, Issue 10, pages 4486-4494, 2009. ( 9/2009 )
  • S. Dowdell, B. Clasie, A. J. Wroe, S. Guatelli, P. Metcalfe, R. Schulte, A. Rosenfeld, The suitability of tissue substitutes for neutron dosimetry in proton therapy, Medical Physics, Volume 36, Issue 12, pages 5412-5419, 2009. ( 4/2009 )
  • Wroe A., Clasie B., Kooy H., Flanz J., Schulte R., and Rosenfeld A., Out-of-field dose equivalents delivered by passively scattered therapeutic proton beams for clinically relevant field configurations. Int J Radiat Oncol Biol Phys. 73, 306-313, 2009. ( 1/2009 )
  • V. Bashkirov, R. Schulte, A.Wroe, A. Breskin, R. Chechik, S. Schemelinin, G. Garty, H. Sadrozinski, E. Gargioni, B. Grosswendt, Experimental Verification of Track Structure Models, IEEE NSS/MIC/RTSD Conference Record, pages 2890-2894, 2008. ( 10/2008 )
  • R. W. Schulte, A. J. Wroe, V. A. Bashkirov, G. Y. Garty, A. Breskin, R. Chechik, S. Shchemelinin, E. Gargioni, B. Grosswendt, and A. B. Rosenfeld, Nanodosimetry-Based Quality Factors for Radiation Protection in Space, Zeitschrift für Medizinische Physik: Special Issue on Medical Physics Aspects of Space Radiation Research, Z. Med. Phys. 18, 286-296, 2008. ( 8/2008 )
  • A. Wroe, A. Rosenfeld, M. Reinhard, V. Pisacane, J. Ziegler, M. Nelson, F. Cucinotta, M. Zaider, J. Dicello, Solid State Microdosimetry with Heavy Ions for Space Applications, IEEE Transactions on Nuclear Science, 54, 6, pp. 2264-2271, 2007. ( 12/2007 )
  • A. J. Wroe, A. B. Rosenfeld, R. W. Schulte; Out-Of-Field Dose Equivalents Delivered by Proton Therapy of Prostate Cancer, Medical Physics, Vol. 34, Issue 9, pp. 3449-3456, 2007. ( 7/2007 )
  • R. Siegele, M. Reinhard, D. Prokopovich, M. Ionescu, D. D. Cohen, A. B. Rosenfeld, I. M. Cornelius, A. Wroe, M. L. F. Lerch, A. Fazzi, A. Pola, and S. Agosteo, Characterisation of a Delta E-E particle telescope using the ANSTO heavy ion microprobe, Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms, vol. 260, pp. 270-275, 2007 ( 4/2007 )
  • I. Cornelius, A. Rosenfeld, M. Reinhard, A. Fazzi, D. Prokopovich, A. Wroe, R. Siegele, A. Pola, S. Agosteo; Charge collection imaging of a monolithic DE-E telescope for radiation protection applications, Radiation Protection Dosimetry, Volume 122, pp. 387-389, 2007 ( 1/2007 )
  • V. Bashkirov, R. Schulte, A. Breskin, R. Chechik, S. Schemelinin, G. Garty, A.Wroe, H. Sadrozinski, B. Grosswendt, Ion-counting nanodosimeter with particle tracking capabilities, Radiation Protection Dosimetry, Volume 122, pp. 415-419, 2006 ( 12/2006 )
  • A. J. Wroe, A. B. Rosenfeld, I. M. Cornelius, D. Prokopovich, M. Reinhard, R. Schulte, V. Bashkirov, Silicon Microdosimetry in Heterogeneous Materials: Simulation & Experiment, IEEE Transactions on Nuclear Science, Volume 53, Issue 6, pp. 3738 – 3744, 2006 ( 12/2006 )
  • Anatoly Rosenfeld, Andrew Wroe, Martin Carolan, Iwan Cornelius, Method of Monte Carlo verification in Hadron Therapy with non-tissue equivalent detectors, SSD 2004 Special Issue Article, Radiation Protection Dosimetry, Volume 116, Issue 1-4, pp. 487-490, 2006. ( 4/2006 )
  • A. J. Wroe, R. Schulte, V. Bashkirov, A.B. Rosenfeld, B. Keeney, P. Spraldin, H.F.W. Sadrozinski, B. Grosswendt, Nanodosimetric Cluster Size Distributions of Therapeutic Proton Beams, IEEE Transactions on Nuclear Science, Volume 53, Issue 2, pp. 532 – 538, 2006 ( 4/2006 )
  • Reinhard Schulte, Vladimir Bashkirov, Sergei Shchemelinin, Amos Breskin, Rachel Chechik, Guy Garty, Andrew Wroe, Bernd Grosswendt, Mapping the Sensitive Volume of an Ion-Counting Nanodosimeter, Journal of Instrumentation, Vol. 1, P04004, April 2006. ( 4/2006 )
  • V. L. Pisacane, Q. E. Dolecek, F. Maas, M. E. Nelson, P. J. Taddei, Z. Zhao, J. F. Ziegler, P. C. Acox, M. Bender, J. D. Brown, T. Garritsen, C. Gaughan, A. Hough, B. Kolb, J. Langlois, J. Ross, M. Sheggeby, D. Thomas, J. F. Dicello, F. A. Cucinotta, M. Zaider, A. B. Rosenfeld, and A. Wroe, MIcroDosimeter iNstrument (MIDN) on MidSTAR-I, SAE Transactions Journal of Aerospace, vol. 2006-01-2146, 2006. ( 1/2006 )
  • A. J. Wroe, I. M. Cornelius, A. B. Rosenfeld, V. L. Pisacane, J. F. Ziegler, M. E. Nelson, F. Cucinotta, M. Zaider, J. F. Dicello, Microdosimetry simulations of solar protons within a spacecraft, IEEE Transactions on Nuclear Science, Volume 52, Issue 6, Part 1, pp. 2591 – 2596, 2005 ( 12/2005 )
  • M. I. Reinhard, I. Cornelius, D. A. Prokopovich, A. Wroe, A. B. Rosenfeld, V.Pisacane, J. F. Ziegler, M. E. Nelson, F. Cucinotta, M. Zaider, and J. F. Dicello, Response of a SOI Microdosimeter to a 238PuBe Neutron Source, IEEE Nuclear Science Symposium Conference Record, 1 (23-29), pp. 68-72, 2005 ( 11/2005 )
  • Reinhard W. Schulte, Vladimir Bashkirov, Márgio C. Loss Klock, Tianfang Li, Andrew J. Wroe, Ivan Evseev, David C. Williams, Todd Satogata, Density resolution of proton computed tomography: Results of a Monte Carlo simulation study, Med Phys. 32, pp. 1035-46, 2005. ( 4/2005 )
  • A. J. Wroe, I. M. Cornelius, A. B. Rosenfeld, Role of inelastic reactions in absorbed dose distribution from proton therapeutic beam in different medium, Med Phys. 32, pp. 37-41, 2005 ( 1/2005 )
  • A. Rosenfeld, A. Wroe, I. Cornelius, D. Alexiev, M. Reinhard Analysis of inelastic interactions for therapeutic proton beam using Monte Carlo simulations, IEEE Trans. on Nucl. Sci , 51, 6, pp. 319-325, 2004 ( 12/2004 )
  • Wroe, A.J.; Schulte, R.; Bashkirov, V.; Rosenfeld, A.B.; Grosswendt, B.; Nanodosimetric cluster size distributions of therapeutic proton beams, Nuclear Science Symposium Conference Record, IEEE Volume 3, pp. 1857 – 1861, 2004 ( 10/2004 )
  • McAuley G A, Slater J M, & Wroe A J. (2014). Single-Plane Magnetically Focused Elongated Small Field Proton Beams. Technol Cancer Res Treat, , . ( 11/2014 - Present ) Link...
    We previously performed Monte Carlo simulations of magnetically focused proton beams shaped by a single quadrapole magnet and thereby created narrow elongated beams with superior dose delivery characteristics (compared to collimated beams) suitable for targets of similar geometry. The present study seeks to experimentally validate these simulations using a focusing magnet consisting of 24 segments of samarium cobalt permanent magnetic material adhered into a hollow cylinder. Proton beams with properties relevant to clinical radiosurgery applications were delivered through the magnet to a water tank containing a diode detector or radiochromic film. Dose profiles were analyzed and compared with analogous Monte Carlo simulations. The focused beams produced elongated beam spots with high elliptical symmetry, indicative of magnet quality. Experimental data showed good agreement with simulations, affirming the utility of Monte Carlo simulations as a tool to model the inherent complexity of a magnetic focusing system. Compared to target-matched unfocused simulations, focused beams showed larger peak to entrance ratios (26% to 38%) and focused simulations showed a two-fold increase in beam delivery efficiency. These advantages can be attributed to the magnetic acceleration of protons in the transverse plane that tends to counteract the particle outscatter that leads to degradation of peak to entrance performance in small field proton beams. Our results have important clinical implications and suggest rare earth focusing magnet assemblies are feasible and could reduce skin dose and beam number while delivering enhanced dose to narrow elongated targets (eg, in and around the spinal cord) in less time compared to collimated beams.
  • Wroe A J, Ghebremedhin A, Gordon I R, Schulte R W, & Slater J D. (2014). Water equivalent thickness analysis of immobilization devices for clinical implementation in proton therapy. Technol Cancer Res Treat, 13(5), 415-20. ( 10/2014 - Present ) Link...
    Immobilization devices can impact not only the inter- and intra-fraction motion of the patient, but also the range uncertainty of the treatment beam in proton therapy. In order to limit additional range uncertainty, the water equivalent thickness (WET) of the immobilization device needs to be well known and accurately reflected in the calculations by the treatment planning system (TPS). The method presented here focusses on the use of a nozzle-mounted variable range shifter and precision-machined polystyrene blocks of known WET to evaluate commercial immobilization devices prior to clinical implementation. CT studies were also completed to evaluate the internal uniformity of the immobilization devices under study. Mul- tiple inserts of the kVue platform (Qfix Systems, Avondale, PA) were evaluated as part of this study. The results indicate that the inserts are largely interchangeable across a given design type and that the measured WET values agree with those generated by the TPS with a maxi- mum difference less than 1 mm. The WET of the devices, as determined by the TPS, was not impacted by CT beam hardening normally experienced during clinical use. The reproduc- ibility of the WET method was also determined to be better than +/-0.02 mm. In conclusion, the testing of immobilization prior to implementation in proton therapy is essential in order to ascertain their impact on the proton treatment and the methodology described here can also be applied to other immobilization systems.
  • Williams K M, Schulte R W, Schubert K E, & Wroe A J. (2014). Evaluation of Mathematical Algorithms for Automatic Patient Alignment in Radiosurgery. Technol Cancer Res Treat, , . ( 9/2014 - Present ) Link...
    Image registration techniques based on anatomical features can serve to automate patient alignment for intracranial radiosurgery procedures in an effort to improve the accuracy and efficiency of the alignment process as well as potentially eliminate the need for implanted fiducial markers. To explore this option, four two-dimensional (2D) image registration algorithms were analyzed: the phase correlation technique, mutual information (MI) maximization, enhanced correlation coefficient (ECC) maximization, and the iterative closest point (ICP) algorithm. Digitally reconstructed radiographs from the treatment planning computed tomography scan of a human skull were used as the reference images, while orthogonal digital x-ray images taken in the treatment room were used as the captured images to be aligned. The accuracy of aligning the skull with each algorithm was compared to the alignment of the currently practiced procedure, which is based on a manual process of selecting common landmarks, including implanted fiducials and anatomical skull features. Of the four algorithms, three (phase correlation, MI maximization, and ECC maximization) demonstrated clinically adequate (ie, comparable to the standard alignment technique) translational accuracy and improvements in speed compared to the interactive, user-guided technique; however, the ICP algorithm failed to give clinically acceptable results. The results of this work suggest that a combination of different algorithms may provide the best registration results. This research serves as the initial groundwork for the translation of automated, anatomy-based 2D algorithms into a real-world system for 2D-to-2D image registration and alignment for intracranial radiosurgery. This may obviate the need for invasive implantation of fiducial markers into the skull and may improve treatment room efficiency and accuracy.
  • Wroe A J, Bush D A, & Slater J D. (2014). Immobilization considerations for proton radiation therapy. Technol Cancer Res Treat, 13(3), 217-26. ( 6/2014 - Present ) Link...
    Proton therapy is rapidly developing as a mainstream modality for external beam radiation therapy. This development is largely due to the ability of protons to deposit much of their energy in a region known as the Bragg peak, minimizing the number of treatment fields and hence integral dose delivered to the patient. Immobilization in radiation therapy is a key component in the treatment process allowing for precise delivery of dose to the target volume and this is certainly true in proton therapy. In proton therapy immobilization needs to not only immobilize the patient, placing them in a stable and reproducible position for each treatment, but its impact on the depth dose distribution and range uncertainty must also be considered. The impact of immobilization on range is not a primary factor in X-ray radiation therapy, but it is a governing factor in proton therapy. This contribution describes the immobilization considerations in proton therapy which have been developed at Loma Linda over twenty plus years of clinical operation as a hospital based proton center.
  • Gridley D S, Pecaut M J, Mao X W, Wroe A J, & Luo-Owen X. (2013). Biological Effects of Passive Versus Active Scanning Proton Beams on Human Lung Epithelial Cells. Technol Cancer Res Treat, , . ( 12/2013 - Present ) Link...
    The goal was to characterize differences in cell response after exposure to active beam scanning (ABS) protons compared to a passive delivery system. Human lung epithelial (HLE) cells were evaluated at various locations along the proton depth dose profile. The dose delivered at the Bragg peak position was essentially identical ( approximately 4 Gy) with the two techniques, but depth dose data showed that ABS resulted in lower doses at entry and more rapid drop-off after the peak. Average dose rates for the passive and ABS beams were 1.1 Gy/min and 5.1 Gy/min, respectively; instantaneous dose rates were 19.2 Gy/min and 2,300 Gy/min (to a 0.5 x 0.5 mm2 voxel). Analysis of DNA synthesis was based on 3H-TdR incorporation. Quantitative real-time polymerase chain reaction (RT-PCR) was done to determine expression of genes related to p53 signaling and DNA damage; a total of 152 genes were assessed. Spectral karyotyping and analyses of the Golgi apparatus and cytokines produced by the HLE cells were also performed. At or near the Bragg peak position, ABS protons resulted in a greater decrease in DNA synthesis compared to passively delivered protons. Genes with .2-fold change (P < 0.05 vs. 0 Gy) after passive proton irradiation at one or more locations within the Bragg curve were BTG2, CDKN1A, IFNB1 and SIAH1. In contrast, many more genes had .2-fold difference with ABS protons: BRCA1, BRCA2, CDC25A, CDC25C, CCNB2, CDK1, DMC1, DNMT1, E2F1, EXO1, FEN1, GADD45A, GTSE1, IL-6, JUN, KRAS, MDM4, PRC1, PTTG1, RAD51, RPA1, TNF, WT1, XRCC2, XRCC3 and XRCC6BP1. Spectral karyotyping revealed numerous differences in chromosomal abnormalities between the two delivery systems, especially at or near the Bragg peak. Percentage of cells staining for the Golgi apparatus was low after exposure to passive and active proton beams. Studies such as this are needed to ensure patient safety and make modifications in ABS delivery, if necessary.
  • Wroe A J, Bush D A, Schulte R W, & Slater J D. (2013). Clinical Immobilization Techniques for Proton Therapy. Technol Cancer Res Treat, , . ( 12/2013 - Present ) Link...
    Proton therapy through the use of the Bragg peak affords clinicians a tool with which highly conformal dose can be delivered to the target while minimizing integral dose to surrounding healthy tissue. To gain maximum benefit from proton therapy adequate patient immobilization must be maintained to ensure accurate dose delivery. While immobilization in external beam radiation therapy is designed to minimize inter- and intra-fraction target motion, in proton therapy there are other additional aspects which must be considered, chief of which is accurately determining and maintaining the targets water-equivalent depth along the beam axis. Over the past 23 years of treating with protons, the team at the James M. Slater Proton Treatment and Research Center at Loma Linda University Medical Center have developed and implemented extensive immobilization systems to address the specific needs of protons. In this publication we review the immobilization systems that are used at Loma Linda in the treatment of head and neck, prostate, upper GI, lung and breast disease, along with a description of the intracranial radiosurgery immobilization system used in the treatment of brain metastasis and arteriovenous malformations (AVM's).
  • Sanzari J K, Wan X S, Krigsfeld G S, Wroe A J, Gridley D S, & Kennedy A R. (2013). The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model. Gravit Space Res, 1(1), 79-94. ( 10/2013 - Present )
    Exposure to total-body radiation induces hematological changes, which can detriment one's immune response to wounds and infection. Here, the decreases in blood cell counts after acute radiation doses of gamma-ray or proton radiation exposure, at the doses and dose-rates expected during a solar particle event (SPE), are reported in the ferret model system. Following the exposure to gamma-ray or proton radiation, the ferret peripheral total white blood cell (WBC) and lymphocyte counts decreased whereas neutrophil count increased within 3 hours. At 48 hours after irradiation, the WBC, neutrophil, and lymphocyte counts decreased in a dose-dependent manner but were not significantly affected by the radiation type (gamma-rays verses protons) or dose rate (0.5 Gy/minute verses 0.5 Gy/hour). The loss of these blood cells could accompany and contribute to the physiological symptoms of the acute radiation syndrome (ARS).
  • Krigsfeld G S, Savage A R, Sanzari J K, Wroe A J, Gridley D S, & Kennedy A R. (2013). Mechanism of hypocoagulability in proton-irradiated ferrets. Int J Radiat Biol, 89(10), 823-831. ( 10/2013 - Present ) Link...
    Purpose : To determine the mechanism of proton radiation-induced coagulopathy. Material and methods: Ferrets were exposed to either solar particle event (SPE)-like proton radiation at a predetermined dose rate of 0.5 Gray (Gy) per hour (h) for a total dose of 0 or 1 Gy. Blood was collected pre- and post-irradiation for a complete blood cell count or a soluble fibrin concentration analysis, to determine whether coagulation activation had occurred. Tissue was stained with an anti-fibrinogen antibody to confirm the presence of fibrin in blood vessels. Results : SPE-like proton radiation exposure resulted in coagulation cascade activation, as determined by increased soluble fibrin concentration in blood from 0.7-2.4 at 3 h, and 9.9 soluble fibrin units (p < 0.05) at 24 h post-irradiation and fibrin clots in blood vessels of livers, lungs and kidneys from irradiated ferrets. In combination with this increase in fibrin clots, ferrets had increased prothrombin time and partial thromboplastin time values post-irradiation, which are representative of the extrinsic/intrinsic coagulation pathways. Platelet counts remained at pre-irradiation values over the course of 7 days, indicating that the observed effects were not platelet-related, but instead likely to be due to radiation-induced effects on secondary hemostasis. White blood cell (WBC) counts were reduced in a statistically significant manner from 24 h through the course of the seven-day experiment. Conclusions : SPE-like proton radiation results in significant decreases in all WBC counts as well as activates secondary hemostasis; together, these data suggest severe risks to astronaut health from exposure to SPE radiation.
  • Sanzari J K, Wan X S, Krigsfeld G S, King G L, Miller A, . . . Kennedy A R. (2013). Effects of Solar Particle Event Proton Radiation on Parameters Related to Ferret Emesis. Radiat Res, 180(2), 166-176. ( 8/2013 - Present ) Link...
    The effectiveness of simulated solar particle event (SPE) proton radiation to induce retching and vomiting was evaluated in the ferret experimental animal model. The endpoints measured in the study included: (1) the fraction of animals that retched or vomited, (2) the number of retches or vomits observed, (3) the latency period before the first retch or vomit and (4) the duration between the first and last retching or vomiting events. The results demonstrated that c ray and proton irradiation delivered at a high dose rate of 0.5 Gy/min induced dose-dependent changes in the endpoints related to retching and vomiting. The minimum radiation doses required to induce statistically significant changes in retching-and vomiting-related endpoints were 0.75 and 1.0 Gy, respectively, and the relative biological effectiveness (RBE) of proton radiation at the high dose rate did not significantly differ from 1. Similar but less consistent and smaller changes in the retching-and vomiting-related endpoints were observed for groups irradiated with c rays and protons delivered at a low dose rate of 0.5 Gy/h. Since this low dose rate is similar to a radiation dose rate expected during a SPE, these results suggest that the risk of SPE radiation-induced vomiting is low and may reach statistical significance only when the radiation dose reaches 1 Gy or higher. (C) 2013 by Radiation Research Society
  • Sanzari J K, Wan X S, Wroe A J, Rightnar S, Cengel K A, . . . Kennedy A R. (2013). Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model. Radiat Res, 180(1), 7-16. ( 7/2013 - Present ) Link...
    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel. (C) 2013 by Radiation Research Society
  • Barnes S, McAuley G, Slater J, & Wroe A. (2013). The effects of mapping CT images to Monte Carlo materials on GEANT4 proton simulation accuracy. Med Phys, 40(4), 7. ( 4/2013 - Present ) Link...
    Purpose: Monte Carlo simulations of radiation therapy require conversion from Hounsfield units (HU) in CT images to an exact tissue composition and density. The number of discrete densities (or density bins) used in this mapping affects the simulation accuracy, execution time, and memory usage in GEANT4 and other Monte Carlo code. The relationship between the number of density bins and CT noise was examined in general for all simulations that use HU conversion to density. Additionally, the effect of this on simulation accuracy was examined for proton radiation. Methods: Relative uncertainty from CT noise was compared with uncertainty from density binning to determine an upper limit on the number of density bins required in the presence of CT noise. Error propagation analysis was also performed on continuously slowing down approximation range calculations to determine the proton range uncertainty caused by density binning These results were verified with Monte Carlo simulations. Results: In the presence of even modest CT noise (5 HU or 0.5%) 450 density bins were found to only cause a 5% increase in the density uncertainty (i.e., 95% of density uncertainty from CT noise, 5% from binning). Larger numbers of density bins are not required as CT noise will prevent increased density accuracy; this applies across all types of Monte Carlo simulations. Examining uncertainty in proton range, only 127 density bins are required for a proton range error of <0.1 mm in most tissue and <0.5 mm in low density tissue (e.g., lung). Conclusions: By considering CT noise and actual range uncertainty, the number of required density bins can be restricted to a very modest 127 depending on the application. Reducing the number of density bins provides large memory and execution time savings in GEANT4 and other Monte Carlo packages. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4793408]
  • Wroe A J, Schulte R W, Barnes S, McAuley G, Slater J D, & Slater J M. (2013). Proton beam scattering system optimization for clinical and research applications. Med Phys, 40(4), 12. ( 4/2013 - Present ) Link...
    Purpose: To develop and test a method for optimizing and constructing a dual scattering system in passively scattered proton therapy. Methods: A beam optics optimization algorithm was developed to optimize the thickness of the first scatterer (S1) and the profile (of both the high-Z material and Lexan) of the second scatterer (S2) to deliver a proton beam matching a given set of parameters, including field diameter, fluence, flatness, and symmetry. A new manufacturing process was also tested that allows the contoured second scattering foil to be created much more economically and quickly using Cerrobend casting. Two application-specific scattering systems were developed and tested using both experimental and Monte Carlo techniques to validate the optimization process described. Results: A scattering system was optimized and constructed to deliver large uniform irradiations of radiobiology samples at low dose rates. This system was successfully built and tested using film and ionization chambers. The system delivered a uniform radiation field of 50 cm diameter (to a dose of +/-7% of the central axis) while the depth dose profile could be tuned to match the specifications of the particular investigator using modulator wheels and range shifters. A second scattering system for intermediate field size (4 cm < diameter < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments was also developed and tested using GEANT4. This system improved beam efficiency by over 70% compared with existing scattering systems while maintaining field flatness and depth dose profile. In both cases the proton range uniformity across the radiation field was maintained, further indicating the accuracy of the energy loss formalism in the optimization algorithm. Conclusions: The methods described allow for rapid prototyping of scattering foils to meet the demands of both research and clinical beam delivery applications in proton therapy. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4793262]
  • McAuley G A, Barnes S R S, Slater J M, & Wroe A J. (2013). Monte Carlo simulation of single-plane magnetically focused narrow proton beams. Phys Med Biol, 58(3), 535-553. ( 2/2013 - Present ) Link...
    We present Monte Carlo simulations of magnetically focused proton beams shaped by a single quadrapole magnet. Such beams are narrowly focused in one longitudinal plane but fan out in the perpendicular plane producing elongated elliptical beam spots (a 'screwdriver' shape). The focused beams were compared to passively collimated beams (the current standard of delivery for small radiosurgery beams). Beam energies considered were relevant to functional radiosurgery and standard radiosurgery clinical applications. Three monoenergetic beams (100, 125, and 150 MeV) and a modulated beam were simulated. Monoenergetic magnetically focused beams demonstrated 28 to 32% lower entrance doses, 31 to 47% larger central peak to entrance depth dose ratios, 26 to 35% smaller integral dose, 25 to 32% smaller estimated therapeutic ratios, 19 to 37% smaller penumbra volumes, and 38 to 65% smaller vertical profile lateral penumbras at Bragg depth, compared to the collimated beams. Focused modulated beams showed 31% larger central peak to entrance dose ratio, and 62 to 65% smaller vertical lateral penumbras over the plateau of the spread out Bragg peak. These advantages can be attributed to the directional acceleration of protons in the transverse plane due to the magnetic field. Such beams can be produced using commercially available assemblies of permanent rare earth magnets that do not require electric power or cryrogenic cooling. Our simulations suggest that these magnets can be inexpensively incorporated into the beam line to deliver reduced dose to normal tissue, and enhanced dose to elongated elliptical targets with major and minor axes on the order of a few centimeters and millimeters, respectively. Such beams may find application in novel proton functional and standard radiosurgery treatments in and around critical structures.
  • Hurley R F, Schulte R W, Bashkirov V A, Wroe A J, Ghebremedhin A, . . . Patyal B. (2012). Water-equivalent path length calibration of a prototype proton CT scanner. Medical Physics, 39(5), 2438-2446. ( 5/2012 - Present ) Link...
    Purpose: The authors present a calibration method for a prototype proton computed tomography (pCT) scanner. The accuracy of these measurements depends upon careful calibration of the energy detector used to measure the residual energy of the protons that passed through the object. Methods: A prototype pCT scanner with a cesium iodide (CsI(Tl)) crystal calorimeter was calibrated by measuring the calorimeter response for protons of 200 and 100 MeV initial energies undergoing degradation in polystyrene plates of known thickness and relative stopping power (RSP) with respect to water. Calibration curves for the two proton energies were obtained by fitting a second-degree polynomial to the water-equivalent path length versus calorimeter response data. Using the 100 MeV calibration curve, the RSP values for a variety of tissue-equivalent materials were measured and compared to values obtained from a standard depth-dose range shift measurement using a water-tank. A cylindrical water phantom was scanned with 200 MeV protons and its RSP distribution was reconstructed using the 200 MeV calibration. Results: It is shown that this calibration method produces measured RSP values of various tissue-equivalent materials that agree to within 0.5% of values obtained using an established water-tank method. The mean RSP value of the water phantom reconstruction was found to be 0.995 +/- 0.006. Conclusions: The method presented provides a simple and reliable procedure for calibration of a pCT scanner. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.3700173]
  • Ziebell A L, Clasie B, Wroe A, Schulte R W, Reinhard M I, . . . Rosenfeld A B. (2011). Solid state diode - Ionization chamber method for measuring out-of-field neutron dose in proton therapy. Radiation Measurements, 46(12), 1638-1642. ( 12/2011 - Present ) Link...
    In proton therapy neutrons are introduced to out-of-field regions inside the patient. Clinicians would like to know the absorbed dose being deposited by neutrons separately to that from protons, so as to be able to directly apply their own dose equivalent weighting factors based on their opinion of the biological risk posed by neutrons in this region. The purpose of this study is to investigate a novel approach to experimentally separating the proton and neutron contributions to the absorbed dose in out-of-field regions. The method pairs specially designed silicon PIN diodes with a standard clinical ionization chamber. The sensitivity of the Si diode to non-ionizing energy losses in silicon is exploited, and can be quantified by measuring the shift in forward voltage for a fixed injection current, pre and post irradiation. The mathematical relations that describe the response of the diode and the ionization chamber can be solved simultaneously to give the contributions to the absorbed dose from protons and neutrons separately. Experimental measurements were made at the Loma Linda University Medical Center (LLUMC), Loma Linda, and Massachusetts General Hospital (MGH), Boston, proton therapy facilities. Experimental separation of the partial proton and neutron contributions to the absorbed dose measured at positions lateral to a typical prostate therapy treatment field delivered to a Lucite phantom was successfully performed and compared with results from a GEANT4 simulation. The experimental results matched well with simulation confirming the validity and promise of the novel approach. (C) 2011 Elsevier Ltd. All rights reserved.
  • Agosteo S, Fazzi A, Introini M V, Pola A, Rosenfeld A B, Shulte R, & Wroe A. (2011). Study of a monolithic silicon telescope for solid state microdosimetry: Response to a 100 MeV proton beam. Radiation Measurements, 46(12), 1529-1533. ( 12/2011 - Present ) Link...
    A monolithic silicon telescope was recently proposed and studied for solid state microdosimetry. It consists of a thin surface Delta E stage (about 2 mu m in thickness), at study for silicon microdosimetry, coupled to an E stage about 500 mu m in thickness, which provide information about the energy of the impinging particle. In order to study the response of the detection system to high energy charged hadrons, the silicon telescope was placed in a polystyrene phantom and irradiated with a 100 MeV un-modulated proton beam at the Loma Linda University Medical Centre. The experimental results were compared with those obtained with a numerical study based on Monte Carlo simulations carried out with the FLUKA code. The agreement between experimental and simulation results was satisfactory. (C) 2011 Elsevier Ltd. All rights reserved.
  • Gridley D S, Freeman T L, Makinde A Y, Wroe A J, Luo-Owen X, . . . Pecaut M J. (2011). Comparison of proton and electron radiation effects on biological responses in liver, spleen and blood. International Journal of Radiation Biology, 87(12), 1173-1181. ( 12/2011 - Present ) Link...
    Purpose: To determine whether differences exist between proton and electron radiations on biological responses after total-body exposure. Materials and methods: ICR mice (n - 45) were irradiated to 2 Gray (Gy) using fully modulated 70 MeV protons (0.5 Gy/min) and 21 MeV electrons (3 Gy/min). At 36 h post-irradiation liver gene expression, white blood cell (WBC), natural killer (NK) cell and other analyses were performed. Results: Oxidative stress-related gene expression patterns were strikingly different for irradiated groups compared to 0 Gy (P < 0.05). Proton radiation up-regulated 15 genes (Ctsb, Dnm2, Gpx5, Il19, Il22, Kif9, Lpo, Nox4, Park7, Prdx4, Prdx6, Rag2, Sod3, Srxn1, Xpa) and down-regulated 2 genes (Apoe, Prdx1). After electron irradiation, 20 genes were up-regulated (Aass, Ctsb, Dnm2, Gpx1, Gpx4, Gpx5, Gpx6, Gstk1, Il22, Kif9, Lpo, Nox4, Park7, Prdx3, Prdx4, Prdx5, Rag2, Sod1, Txnrd3, Xpa) and 1 was down-regulated (Mpp4). Of the modified genes, only 11 were common to both forms of radiation. Comparison between the two irradiated groups showed that electrons significantly up-regulated three genes (Gstk1, Prdx3, Scd1). Numbers of WBC and major leukocyte types were low in the irradiated groups (P < 0.001 vs. 0 Gy). Hemoglobin and platelet counts were low in the electron-irradiated group (P < 0.05 vs. 0 Gy). However, spleens from electron-irradiated mice had higher WBC and lymphocyte counts, as well as enhanced NK cell cytotoxicity, compared to animals exposed to protons (P < 0.05). There were no differences between the two irradiated groups in body mass, organ masses, and other assessed parameters, although some differences were noted compared to 0 Gy. Conclusion: Collectively, the data demonstrate that at least some biological effects induced by electrons may not be directly extrapolated to protons.
  • Maks C J, Wan X S, Ware J H, Romero-Weaver A L, Sanzari J K, . . . Kennedy A R. (2011). Analysis of White Blood Cell Counts in Mice after Gamma- or Proton-Radiation Exposure. Radiation Research, 176(2), 170-176. ( 8/2011 - Present ) Link...
    Maks, C. J., Wan, X. S., Ware, J. H., Romero-Weaver, A. L., Sanzari, J. K., Wilson, J. M., Rightnar, S., Wroe, A. J., Koss, P., Gridley, D. S., Slater, J. M. and Kennedy, A. R. Analysis of White Blood Cell Counts in Mice after Gamma- or Proton-Radiation Exposure. Radiat. Res. 176, 170-176 (2011). In the coming decades human space exploration is expected to move beyond low-Earth orbit. This transition involves increasing mission time and therefore an increased risk of radiation exposure from solar particle event (SPE) radiation. Acute radiation effects after exposure to SPE radiation are of prime importance due to potential mission-threatening consequences. The major objective of this study was to characterize the dose-response relationship for proton and gamma radiation delivered at doses up to 2 Gy at high (0.5 Gy/min) and low (0.5 Gy/h) dose rates using white blood cell (WBC) counts as a biological end point. The results demonstrate a dose-dependent decrease in WBC counts in mice exposed to high- and low-dose-rate proton and gamma radiation, suggesting that astronauts exposed to SPE-like radiation may experience a significant decrease in circulating leukocytes. (C) 2011 by Radiation Research Society
  • Dicello J F, Gersey B B, Gridley D S, Coutrakon G B, Lesyna D, . . . Slater J M. (2011). MICRODOSIMETRIC COMPARISON OF SCANNED AND CONVENTIONAL PROTON BEAMS USED IN RADIATION THERAPY. Radiation Protection Dosimetry, 143(2-4), 513-518. ( 2/2011 - Present ) Link...
    Multiple groups have hypothesised that the use of scanning beams in proton therapy will reduce the neutron component of secondary radiation in comparison with conventional methods with a corresponding reduction in risks of radiation-induced cancers. Loma Linda University Medical Center (LLUMC) has had FDA marketing clearance for scanning beams since 1988 and an experimental scanning beam has been available at the LLUMC proton facility since 2001. The facility has a dedicated research room with a scanning beam and fast switching that allows its use during patient treatments. Dosimetric measurements and microdosimetric distributions for a scanned beam are presented and compared with beams produced with the conventional methods presently used in proton therapy.
  • Gridley D S, Grover R S, Loredo L N, Wroe A J, & Slater J D. (2010). Proton-beam therapy for tumors of the CNS. Expert Review of Neurotherapeutics, 10(2), 319-330. ( 2/2010 - Present ) Link...
    The focus of this review is proton radiotherapy for primary neoplasms of the brain. Although glial cells are among the most radioresistant in the body, the presence of sensitive critical structures and the high doses needed to control CNS tumors present a formidable challenge to the treating radiation oncologist. Treatment with conventional photon radiation at doses required to control disease progression all too often results in unacceptable toxicity. Protons have intrinsic properties that often allow radiation oncologists to deliver a higher dose to the tumor compared with photons, while at the same time offering better sparing of normal tissues. Recognition of these advantages has resulted in development of many new proton treatment facilities worldwide.
  • Clasie B, Wroe A, Kooy H, Depauw N, Flanz J, Paganetti H, & Rosenfeld A. (2010). Assessment of out-of-field absorbed dose and equivalent dose in proton fields. Medical Physics, 37(1), 311-321. ( 1/2010 - Present ) Link...
    Purpose: In proton therapy, as in other forms of radiation therapy, scattered and secondary particles produce undesired dose outside the target volume that may increase the risk of radiation-induced secondary cancer and interact with electronic devices in the treatment room. The authors implement a Monte Carlo model of this dose deposited outside passively scattered fields and compare it to measurements, determine the out-of-field equivalent dose, and estimate the change in the dose if the same target volumes were treated with an active beam scanning technique. Methods: Measurements are done with a thimble ionization chamber and the Wellhofer MatriXX detector inside a Lucite phantom with field configurations based on the treatment of prostate cancer and medulloblastoma. The authors use a GEANT4 Monte Carlo simulation, demonstrated to agree well with measurements inside the primary field, to simulate fields delivered in the measurements. The partial contributions to the dose are separated in the simulation by particle type and origin. Results: The agreement between experiment and simulation in the out-of-field absorbed dose is within 30% at 10-20 cm from the field edge and 90% of the data agrees within 2 standard deviations. In passive scattering, the neutron contribution to the total dose dominates in the region downstream of the Bragg peak (65%-80% due to internally produced neutrons) and inside the phantom at distances more than 10-15 cm from the field edge. The equivalent doses using 10 for the neutron weighting factor at the entrance to the phantom and at 20 cm from the field edge are 2.2 and 2.6 mSv/Gy for the prostate cancer and cranial medulloblastoma fields, respectively. The equivalent dose at 15-20 cm from the field edge decreases with depth in passive scattering and increases with depth in active scanning. Therefore, active scanning has smaller out-of-field equivalent dose by factors of 30-45 in the entrance region and this factor decreases with depth. Conclusions: The dose deposited immediately downstream of the primary field, in these cases, is dominated by internally produced neutrons; therefore, scattered and scanned fields may have similar risk of second cancer in this region. The authors confirm that there is a reduction in the out-of-field dose in active scanning but the effect decreases with depth. GEANT4 is suitable for simulating the dose deposited outside the primary field. The agreement with measurements is comparable to or better than the agreement reported for other implementations of Monte Carlo models. Depending on the position, the absorbed dose outside the primary field is dominated by contributions from primary protons that may or may not have scattered in the brass collimating devices. This is noteworthy as the quality factor of the low LET protons is well known and the relative dose risk in this region can thus be assessed accurately. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3271390]
  • Dowdell S, Clasie B, Wroe A, Guatelli S, Metcalfe P, Schulte R, & Rosenfeld A. (2009). Tissue equivalency of phantom materials for neutron dosimetry in proton therapy. Medical Physics, 36(12), 5412-5419. ( 12/2009 - Present ) Link...
    Purpose: Previous Monte Carlo and experimental studies involving secondary neutrons in proton therapy have employed a number of phantom materials that are designed to represent human tissue. In this study, the authors determined the suitability of common phantom materials for dosimetry of secondary neutrons, specifically for pediatric and intracranial proton therapy treatments. Methods: This was achieved through comparison of the absorbed dose and dose equivalent from neutrons generated within the phantom materials and various ICRP tissues. The phantom materials chosen for comparison were Lucite, liquid water, solid water, and A150 tissue equivalent plastic. These phantom materials were compared to brain, muscle, and adipose tissues. Results: The magnitude of the doses observed were smaller than those reported in previous experimental and Monte Carlo studies, which incorporated neutrons generated in the treatment head. The results show that for both neutron absorbed dose and dose equivalent, no single phantom material gives agreement with tissue within 5% at all the points considered. Solid water gave the smallest mean variation with the tissues out of field where neutrons are the primary contributor to the total dose. Conclusions: Of the phantom materials considered, solid water shows best agreement with tissues out of field. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3250857]
  • Wroe A, Schulte R, Fazzi A, Pola A, Agosteo S, & Rosenfeld A. (2009). RBE estimation of proton radiation fields using a Delta E-E telescope. Medical Physics, 36(10), 4486-4494. ( 10/2009 - Present ) Link...
    A new monolithic silicon Delta E-E telescope was evaluated in unmodulated and modulated 100 MeV proton beams used for hadron therapy. Compared to a classical microdosimetry detector, which provides one-dimensional information on lineal energy of charged particles, this detector system provides two-dimensional information on lineal energy and particle energy based on energy depositions, collected in coincidence, within the Delta E and E stages of the detector. The authors investigated the possibility to use the information obtained with the Delta E-E telescope to determine the relative biological effectiveness (RBE) at defined locations within the proton Bragg peak and spread-out Bragg peak (SOBP). An RBE matrix based on the established in vitro V79 cell survival data was developed to link the output of the device directly to RBE(alpha), the RBE in the low-dose limit, at various depths in a homogeneous polystyrene phantom. In the SOBP of a 100 MeV proton beam, the RBE(alpha) increased from 4.04 proximal to the SOBP to a maximum value of 5.4 at the distal edge. The Delta E-E telescope, with its high spatial resolution, has potential applications to biologically weighted hadron treatment planning as it provides a compact and portable means for estimating the RBE in rapidly changing hadron radiation fields within phantoms. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3215927]
  • Bashkirov V, Schulte R, Wroe A, Sadrozinski H, Gargioni E, & Grosswendt B. (2009). Experimental Validation of Track Structure Models. Ieee Transactions on Nuclear Science, 56(5), 2859-2863. ( 10/2009 - Present ) Link...
    A tracking ion counting nanodosimeter was employed to acquire spatial ionization patterns produced by charged particles in propane gas at 1.3 mbar. Data were taken at the James M. Slater MD Proton Treatment and Research Center with 250 MeV, 17 MeV, 5 MeV and 1.5 MeV proton beams, 4.8 MeV alpha particles and electrons from a Sr-90/Y-90 source. For each particle type, measurable quantities used for track structure reconstruction included the number of ionizations and their location within a wall-less, cylindrical sensitive volume measured with a resolution of about 5 tissue-equivalent nanometers, and primary particle coordinates. Measured ionization frequency distributions as a function of distance from particle track were compared with results of a dedicated Monte Carlo track structure code.
  • Wroe A, Clasie B, Kooy H, Flanz J, Schulte R, & Rosenfeld A. (2009). OUT-OF-FIELD DOSE EQUIVALENTS DELIVERED BY PASSIVELY SCATTERED THERAPEUTIC PROTON BEAMS FOR CLINICALLY RELEVANT FIELD CONFIGURATIONS. International Journal of Radiation Oncology Biology Physics, 73(1), 306-313. ( 1/2009 - Present ) Link...
    Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement from the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields. (C) 2009 Elsevier Inc.
  Books and Chapters
  • Andrew Wroe, Steven Rightnar: Shielding and Radioprotection in Ion Beam Therapy Facilities, Ion Beam Therapy, Springer, 2011. ( 4/2011 )
  • James Slater, Jerry Slater, Andrew Wroe.; Proton radiation therapy in the hospital environment: conception, development, and operation of the initial hospital-based facility, Reviews of Accelerator Science and Technology Vol. 2, World Scientific, 2009. ( 12/2009 )
  Non-Scholarly Journals
  • A. J. Wroe, J. D. Slater, J. M. Slater, The Physics of Protons for Patient Treatment, NASA Health Risks of Extraterrestrial Environment Encyclopedia ( 9/2012 ) Link...
  • Schulte R W, Hurley R F, Wroe A J, & Bashkirov V A. (2013). First Experience With an Experimental Proton CT Scanner. International Journal of Radiation Oncology Biology Physics, 87(2), S44-S44. ( 10/2013 - Present )
  • Wroe A, Schulte R, Slater J D, & Slater J M. (2012). Immobilization for Proton Therapy - How Is It Different to Photon Therapy?. Medical Physics, 39(6), 3780-3780. ( 6/2012 - Present )