James M. Slater

Loma Linda University, لوما ليندا، كاليفورنيا, California, United States

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Publications (178)528.87 Total impact

  • G A McAuley · J M Slater · J D Slater · AJ Wroe
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    ABSTRACT: To investigate the use of magnetic focusing for small field proton irradiations. It is hypothesized that magnetic focusing will provide significant dose distribution benefits over standard collimated beams for fields less than 10 mm diameter. Magnets consisting of 24 segments of radiation hard samarium-cobalt adhered into hollow cylinders were designed and manufactured. Two focusing magnets were placed on a positioning track on our Gantry 1 treatment table. Proton beams with energies of 127 and 157 MeV, 15 and 30 mm modulation, and 8 mm initial diameters were delivered to a water tank using single-stage scattering. Depth dose distributions were measured using a PTW PR60020 diode detector and transverse profiles were measured with Gafchromic EBT3 film. Monte Carlo simulations were also performed - both for comparison with experimental data and to further explore the potential of magnetic focusing in silica. For example, beam spot areas (based on the 90% dose contour) were matched at Bragg depth between simulated 100 MeV collimated beams and simulated beams focused by two 400 T/m gradient magnets. Preliminary experimental results show 23% higher peak to entrance dose ratios and flatter spread out Bragg peak plateaus for 8 mm focused beams compared with uncollimated beams. Monte Carlo simulations showed 21% larger peak to entrance ratios and a ∼9 fold more efficient dose to target delivery compared to spot-sized matched collimated beams. Our latest results will be presented. Our results suggest that rare earth focusing magnet assemblies could reduce skin dose and beam number while delivering dose to nominally spherical radiosurgery targets over a much shorter time compared to unfocused beams. Immediate clinical applications include those associated with proton radiosurgery and functional radiosurgery of the brain and spine, however expanded treatment sites can be also envisaged.
    No preview · Article · Jun 2015 · Medical Physics
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    ABSTRACT: The small fields and sharp gradients typically encountered in proton radiosurgery require high spatial resolution dosimetric measurements, especially below 1–2 cm diameters. Radiochromic film provides high resolution, but requires postprocessing and special handling. Promising alternatives are diode detectors with small sensitive volumes (SV) that are capable of high resolution and real-time dose acquisition. In this study we evaluated the PTW PR60020 proton dosimetry diode using radiation fields and beam energies relevant to radiosurgery applications. Energies of 127 and 157 MeV (9.7 to 15 cm range) and initial diameters of 8, 10, 12, and 20mm were delivered using single-stage scattering and four modulations (0, 15, 30, and 60mm) to a water tank in our treatment room. Depth dose and beam profile data were compared with PTW Markus N23343 ionization chamber, EBT2 Gafchromic film, and Monte Carlo simulations. Transverse dose profiles were measured using the diode in “edge-on” orientation or EBT2 film. Diode response was linear with respect to dose, uniform with dose rate, and showed an orientation-dependent (i.e., beam parallel to, or perpendicular to, detector axis) response of less than 1%. Diodevs. Markus depth-dose profiles, as well as Markus relative dose ratio vs. simulated dose-weighted average lineal energy plots, suggest that any LET-dependent diode response is negligible from particle entrance up to the very distal portion of the SOBP for the energies tested. Finally, while not possible with the ionization chamber due to partial volume effects, accurate diode depth-dose measurements of 8, 10, and 12mm diameter beams were obtained compared to Monte Carlo simulations. Because of the small SV that allows measurements without partial volume effects and the capability of submillimeter resolution (in edge-on orientation) that is crucial for small fields and high-dose gradients (e.g., penumbra, distal edge), as well as negligible LET dependence over nearly the full the SOBP, the PTW proton diode proved to be a useful high-resolution, real-time metrology device for small proton field radiation measurements such as would be encountered in radiosurgery applications.
    Full-text · Book · Jan 2015
  • Grant A McAuley · James M Slater · Andrew J Wroe
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    ABSTRACT: 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. © The Author(s) 2014.
    No preview · Article · Nov 2014 · Technology in cancer research & treatment

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
  • A Teran · G McAuley · J D Slater · J M Slater · A Wroe
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    ABSTRACT: Purpose: To test the PTW PR60020 proton dosimetry diode in radiation fields relevant to proton radiosurgery applications and evaluate its suitability as a high resolution, real time dosimetry device.
    No preview · Article · Jun 2014 · Medical Physics

  • No preview · Article · Oct 2013 · International Journal of Radiation OncologyBiologyPhysics
  • A J Wroe · R W Schulte · S Barnes · G McAuley · J D Slater · J M Slater
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    ABSTRACT: 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.
    No preview · Article · Apr 2013 · Medical Physics
  • Samuel Barnes · Grant McAuley · James Slater · Andrew Wroe
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    ABSTRACT: 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.
    No preview · Article · Apr 2013 · Medical Physics
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    G A McAuley · S R S Barnes · J M Slater · A J Wroe
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    ABSTRACT: 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.
    Full-text · Article · Jan 2013 · Physics in Medicine and Biology
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    ABSTRACT: To evaluate the efficacy of fractionated proton radiotherapy for a population of patients with benign cavernous sinus meningiomas. Between 1991 and 2002, 72 patients were treated at Loma Linda University Medical Center with proton therapy for cavernous sinus meningiomas. Fifty-one patients had biopsy or subtotal resection; 47 had World Health Organization grade 1 pathology. Twenty-one patients had no histologic verification. Twenty-two patients received primary proton therapy; 30 had 1 previous surgery; 20 had more than 1 surgery. The mean gross tumor volume was 27.6 cm(3); mean clinical target volume was 52.9 cm(3). Median total doses for patients with and without histologic verification were 59 and 57 Gy, respectively. Mean and median follow-up periods were 74 months. The overall 5-year actuarial control rate was 96%; the control rate was 99% in patients with grade 1 or absent histologic findings and 50% for those with atypical histology. All 21 patients who did not have histologic verification and 46 of 47 patients with histologic confirmation of grade 1 tumor demonstrated disease control at 5 years. Control rates for patients without previous surgery, 1 surgery, and 2 or more surgeries were 95%, 96%, and 95%, respectively. Fractionated proton radiotherapy for grade 1 cavernous sinus meningiomas achieves excellent control rates with minimal toxicities, regardless of surgical intervention or use of histologic diagnosis. Disease control for large lesions can be achieved by primary fractionated proton therapy.
    No preview · Article · Aug 2012 · International journal of radiation oncology, biology, physics
  • Benjamin H. S.lau · Douglas S.wong · James M.slater
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    ABSTRACT: Of 22 subjects with allertic rhinitis who received a series of 6 acupuncture treatments, 11 (50%) were virtually symptom-free by the end of the series, 8 (36%) experienced a moderate reduction in symptoms, and 3 (14%) recieved no significant relief. Clinical assessment of symptoms was made on a 6-point scale before the first treatment and before each subsequent session. Laboratory tests included absolute blood eosinophils, percentage of nasal eosinophils, and radioimmunoassy of serum IgE, performed before the first treatment, at the end of the series, and 2 months later. A siginificant decrease in subjective clinical rating symptoms correlated with a concurrent drop in absolute numbers of blood eosinophils and percentage of nasal eosinophils. IgE levels decreased in 64% of the subjects by completion of treatment and in 76% at 2-month follow-up.
    No preview · Article · Apr 2012 · The American Journal of Chinese Medicine
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    ABSTRACT: Due to radiation-induced immune depression and development of pathologies such as cancer, there is increasing urgency to identify radiomitigators that are effective when administered after radiation exposure. The main goal of this study was to determine the radiomitigation capacity of MnTE-2-PyP[Mn(III) tetrakis (N-ethylpyridinium-2-yl) porphyrin], a superoxide dismutase (SOD) mimetic, and evaluate leukocyte parameters in spleen and blood. C57BL/6 mice were total-body exposed to 2 Gy γ-rays (Co-60), i.e., well below a lethal dose, followed by subcutaneous implantation of 5 3 10(5) RM-9 prostate tumor cells and initiation of MnTE-2-PyP treatment (day 0); interval between each procedure was 1-2 h. The drug was administered daily (12 times). Tumor progression was monitored and immunological analyses were performed on a subset per group on day 12. Animals treated with MnTE-2-PyP alone had significantly slower tumor growth compared to mice that did not receive the drug (P < 0.05), while radiation alone had no effect. Treatment of tumor-bearing mice with MnTE-2-PyP alone significantly increased spleen mass relative to body mass; the numbers of splenic white blood cells (WBC) and lymphocytes (B and T), as well as circulating WBC, granulocytes, and platelets, were high compared to one of more of the other groups (P <  0.05). The results show that MnTE-2-PyP slowed RM-9 tumor progression and up-regulated immune parameters, but mitigation of the effects of 2 Gy total-body irradiation were minimal. Key words: Ionizing radiation; Oxidative stress; Cancer; Leukocytes; Lymphocytes.
    Full-text · Article · Mar 2012 · Technology in cancer research & treatment
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    S.R.S. Barnes · G.A. McAuley · J.M. Slater · A.J. Wroe
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    ABSTRACT: Simulations of a clinical proton treatment nozzle with GEANT4 were performed and compared against measured data to assess simulation accuracy. Various parameters were then adjusted to examine their effect of accuracy and determine optimal values. This analysis included GEANT version (9.3 and 9.5), range cuts, step max, and initial beam model. GEANT4 version 9.5 was found to give better range accuracy than version 9.3. Simulation accuracy was found to not be very sensitive to range cuts and step max parameters, but recommended values for high accuracy simulations are 250 11m for range cuts and 0.1 mm for step max. Finally, the initial beam model was shown to change the lateral profile in the phantom, however, lateral profiles still show significantly higher error rates than depth profiles.
    Full-text · Conference Paper · Jan 2012
  • James M. Slater
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    ABSTRACT: Radiation therapy (RT) developed in several eras. Patients' needs for more effective treatment guided the efforts. The development of ion beam therapy (IBT) can be seen as a corollary in this continuous endeavor to optimize disease control while minimizing normal-tissue damage. It could not have materialized, however, without the curiosity, ingenuity, and perseverance of researchers, engineers, and clinicians who developed important enabling technologies.
    No preview · Article · Jan 2012
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    ABSTRACT: Raw data derived from mass spectroscopic (MS) analyses of formalin-fixed paraffin-embedded (FFPE) tissue sections of the essential metabolic organ, liver, allocated by the provider (Amgen) from mice subjected to 13 days of microgravity on NASA Flight STS-118 were analyzed by two different search engines, using shotgun proteomics. With the eight statistically significant readouts in hand, Ingenuity Pathway Analysis (IPA) was employed to visualize probable biologic pathway relationships among proteins that might be associated with alterations in liver biochemistry due to space flight. Most noteworthy was the finding of up-regulation of the first urea cycle enzyme carbamoylphosphate synthetase, consistent with increased amino acid catabolism resulting from gravitational changes, and/ or other stress associated with missions in space. Down-regulation of fructose-bisphosphate aldolase B, regucalcin, ribonuclease UK114, alpha enolase, glycine N-methyltransferase and S-adenosyl methionine synthetase isoform type-1 was observed. 60 kDa heat shock protein was elevated.
    No preview · Article · Jan 2012 · Journal of Proteomics & Bioinformatics
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    ABSTRACT: To determine whether differences exist between proton and electron radiations on biological responses after total-body exposure. 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. 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. Collectively, the data demonstrate that at least some biological effects induced by electrons may not be directly extrapolated to protons.
    No preview · Article · Dec 2011 · International Journal of Radiation Biology
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    ABSTRACT: The James M. Slater, M.D. Proton Therapy Treatment and Research Center of the Loma Linda University Medical Center (LLUMC) has treated more than 15,000 patients with proton beams since its inception in 1990, and it is responsible for the majority of patients treated with protons in a hospital setting. Moreover, it is one of only a few institutions with approval by the Federal Drug Administration to treat patients with dynamically scanned proton beams with such beams available presently for experimentation at LLUMC. These features place LLUMC in a unique position for determining improved estimates of outcomes and risks associated with proton therapy including more precise risk estimates for second cancers in patients treated with active or passive proton delivery systems An ancillary benefit in the context of establishing the risks of doses in medical applications is that it would provide a much more solid basis for the estimation of effective doses and the application of microdosimetric spectral analyses to such risk estimations. Such results are important as both the number of institutions treating with protons and the number of patients treated with protons will be increasing rapidly over the next few years.
    No preview · Article · Dec 2011 · Radiation Measurements
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    Jerry R. Williams · Daila S. Gridley · James M. Slater

    Full-text · Chapter · Nov 2011
  • C. R. Sila · R. Schulte · R. Levy · J. D. Slater · J. M. Slater

    No preview · Article · Oct 2011 · Fuel and Energy Abstracts
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    ABSTRACT: The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.
    No preview · Article · Aug 2011 · Radiation Research

Publication Stats

4k Citations
528.87 Total Impact Points


  • 1974-2015
    • Loma Linda University
      • • Department of Radiation Medicine
      • • Department of Gynecology and Obstetrics
      • • Division of Biochemistry
      • • Division of Microbiology
      • • Department of Radiology
      • • Department of Medicine
      لوما ليندا، كاليفورنيا, California, United States
  • 2002
    • Zentralklinik Bad Berka
      Bad Berka, Thuringia, Germany
  • 1999
    • University of Innsbruck
      Innsbruck, Tyrol, Austria