Reinhard W. Schulte

Out-of-field dose equivalents delivered by proton therapy of prostate cancer

Measurements were performed to assess the dose equivalent outside a primary proton treatment field, using a silicon-on-insulator (SOI) microdosimeter. The SOI microdosimeter was placed on the surface of an anthropomorphic phantom and dose equivalents were determined as a function of lateral distance from a typical passively scattered and modulated prostate treatment field. Measurements were also completed within a polystyrene plate phantom as a function of depth for a distance of 5 cm from the field edge, as function of lateral distance from field edge at two different depths, and as a function of distance from the distal edge on the central beam axis. The dose equivalent at the surface of the anthropomorphic phantom decreases from 3.9 to 0.18 mSv/Gy when the lateral distance from the proton field edge increases from 2.5 to 60 cm. Measurements along the proton depth dose distribution at a constant distance of 5 cm from the primary field edge indicate a decrease in dose equivalent as a function of depth, with a 38% decrease relative to the surface dose at a depth of 5 cm in polystyrene. Measurements completed as a function of lateral distance from the primary field at two separate depths within polystyrene illustrate a convergence of the dose equivalent at approximately 20 cm from the primary field edge. Past the distal edge of the spread-out Bragg peak dose equivalents decrease exponentially for increasing distance, with an initial value of 1.6 mSv/Gy at 0.6 cm from the distal edge. Silicon microdosimetry measurements were also compared with published results obtained utilizing different measurement techniques. This study demonstrates the applicability of SOI microdosimetry in determining the dose equivalent outside proton treatment fields, and provides valuable information on the dose equivalent both at the surface and at depth experienced by prostate cancer patients treated with protons.

Reconstruction for proton computed tomography by tracing proton trajectories: A Monte Carlo study

Proton computed tomography (pCT) has been explored in the past decades because of its unique imaging characteristics, low radiation dose, and its possible use for treatment planning and on-line target localization in proton therapy. However, reconstruction of pCT images is challenging because the proton path within the object to be imaged is statistically affected by multiple Coulomb scattering. In this paper, we employ GEANT4-based Monte Carlo simulations of the two-dimensional pCT reconstruction of an elliptical phantom to investigate the possible use of the algebraic reconstruction technique (ART) with three different path-estimation methods for pCT reconstruction. The first method assumes a straight-line path (SLP) connecting the proton entry and exit positions, the second method adapts the most-likely path (MLP) theoretically determined for a uniform medium, and the third method employs a cubic spline path (CSP). The ART reconstructions showed progressive improvement of spatial resolution when going from the SLP [2 line pairs (lp) cm(-1)] to the curved CSP and MLP path estimates (5 lp cm(-1)). The MLP-based ART algorithm had the fastest convergence and smallest residual error of all three estimates. This work demonstrates the advantage of tracking curved proton paths in conjunction with the ART algorithm and curved path estimates.

Density resolution of proton computed tomography

Conformal proton radiation therapy requires accurate prediction of the Bragg peak position. Protons may be more suitable than conventional x-rays for this task since the relative electron density distribution can be measured directly with proton computed tomography (CT). However, proton CT has its own limitations, which need to be carefully studied before this technique can be introduced into routine clinical practice. In this work, we have used analytical relationships as well as the Monte Carlo simulation tool GEANT4 to study the principal resolution limits of proton CT. The noise level observed in proton CT images of a cylindrical water phantom with embedded tissue-equivalent density inhomogeneities, which were generated based on GEANT4 simulations, compared well with predictions based on Tschalars theory of energy loss straggling. The relationship between phantom thickness, initial energy, and the relative electron density resolution was systematically investigated to estimate the proton dose needed to obtain a given density resolution. We show that a reasonable density resolution can be achieved with a relatively small dose, which is comparable to or even lower than that of x-ray CT.

A maximum likelihood proton path formalism for application in proton computed tomography

The limited spatial resolution in proton computed tomography (pCT) in comparison to x-ray CT is related to multiple Coulomb scattering (MCS) within the imaged object. The current generation pCT design utilizes silicon detectors that measure the position and direction of individual protons prior to and post-traversing the patient to maximize the knowledge of the path of the proton within the imaged object. For efficient reconstruction with the proposed pCT system, one needs to develop compact and flexible mathematical formalisms that model the effects of MCS as the proton traverses the imaged object. In this article, a compact, matrix-based most likely path (MLP) formalism is presented employing Bayesian statistics and a Gaussian approximation of MCS. Using GEANT4 simulations in a homogeneous 20 cm water cube, the MLP expression was found to be able to predict the Monte Carlo tracks of 200 MeV protons to within 0.6 mm on average when employing 3sigma cuts on the relative exit angle and exit energy. These cuts were found to eliminate the majority of events not conforming to the Gaussian model of MCS used in the MLP derivation. M riszwana Banu

Total variation superiorization schemes in proton computed tomography image reconstruction

PURPOSE Iterative projection reconstruction algorithms are currently the preferred reconstruction method in proton computed tomography (pCT). However, due to inconsistencies in the measured data arising from proton energy straggling and multiple Coulomb scattering, the noise in the reconstructed image increases with successive iterations. In the current work, the authors investigated the use of total variation superiorization (TVS) schemes that can be applied as an algorithmic add-on to perturbation-resilient iterative projection algorithms for pCT image reconstruction. METHODS The block-iterative diagonally relaxed orthogonal projections (DROP) algorithm was used for reconstructing GEANT4 Monte Carlo simulated pCT data sets. Two TVS schemes added on to DROP were investigated; the first carried out the superiorization steps once per cycle and the second once per block. Simplifications of these schemes, involving the elimination of the computationally expensive feasibility proximity checking step of the TVS framework, were also investigated. The modulation transfer function and contrast discrimination function were used to quantify spatial and density resolution, respectively. RESULTS With both TVS schemes, superior spatial and density resolution was achieved compared to the standard DROP algorithm. Eliminating the feasibility proximity check improved the image quality, in particular image noise, in the once-per-block superiorization, while also halving image reconstruction time. Overall, the greatest image quality was observed when carrying out the superiorization once per block and eliminating the feasibility proximity check. CONCLUSIONS The low-contrast imaging made possible with TVS holds a promise for its incorporation into future pCT studies.

Combined proton and photon conformal radiation therapy for locally advanced carcinoma of the prostate: Preliminary results of a phase I II study

PURPOSE A study was developed to evaluate the use of combined photons and protons for the treatment of locally advanced carcinoma of the prostate. This report is a preliminary assessment of treatment-related morbidity and tumor response. METHODS AND MATERIALS One hundred and six patients in stages T2b (B2), T2c (B2), and T3 (C) were treated with 45 Gy photon-beam irradiation to the pelvis and an additional 30 Cobalt Gray Equivalent (CGE) to the prostate with 250-MeV protons, yielding a total prostate dose of 75 CGE in 40 fractions. Median follow-up time was 20.2 months (range: 10-30 months). Toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) grading system; local control was evaluated by serial digital rectal examination (DRE) and prostate specific antigen (PSA) measurements. RESULTS Morbidity evaluation was available on 104 patients. The actuarial 2-year rate of Grade 1 or 2 late morbidity was 12% (8% rectal, 4% urinary). No patients demonstrated Grade 3 or 4 late morbidity. Treatment response was evaluated on 100 patients with elevated pretreatment serum PSA levels. The actuarial 2-year rate of PSA normalization was 96%, 97%, and 63% for pretreatment PSAs of > 4-10, > 10-20, and > 20, respectively. The 13 patients with rising PSA demonstrated local recurrence (3 patients), distant metastasis (8 patients), or no evidence of disease except increasing PSA (2 patients). CONCLUSIONS The low incidence of side effects, despite the tumor dose of 75 CGE, demonstrates that conformal protons can deliver higher doses of radiation to target tissues without increasing complications to surrounding normal tissues. The initial tumor response, as assessed by the high actuarial rate of normalization with pretreatment PSA < or = 20, and the low rate of recurrences within the treatment field (2.8%), are encouraging.

Proton therapy for pediatric cranial tumors: Preliminary report on treatment and disease-related morbidities

PURPOSE Accelerated protons were used in an attempt to limit treatment-related morbidity in children with tumors in or near the developing brain, by reducing the integral dose to adjacent normal tissues. METHODS AND MATERIALS Children treated with protons at Loma Linda University Medical Center between August 1991 and December 1994 were analyzed retrospectively. Twenty-eight children, aged 1 to 18 years, were identified as at risk for brain injury from treatment. Medical records, physical examinations, and correspondence with patients, their parents, and referring physicians were analyzed. The investigators tabulated post-treatment changes in pre-treatment signs and symptoms and made judgments as to whether improvement, no change, or worsening related to disease or treatment had supervened. Magnetic resonance images were correlated with clinical findings and radiographic impressions were tabulated. RESULTS Follow-up ranged from 7 to 49 months (median 25 months). Four instances of treatment-related morbidity were identified. Forty-one instances of site-specific, disease-related morbidity were identified: 15 improved or resolved and 26 remained unchanged after treatment. Four patients had radiographic evidence of local failure. Three of these patients, including two with high-grade glioma, have died. CONCLUSION Early treatment-related morbidity associated with proton therapy is low. Tumor progression remains a problem when treating certain histologies such as high-grade glioma. Escalating the dose delivered to target volumes may benefit children with tumors associated with poor rates of local control. Long-term follow-up, including neurocognitive testing, is in progress to assess integral-dose effects on cognitive, behavioral and developmental outcomes in children with cranial tumors.

The performance of a novel ion-counting nanodosimeter

Abstract We present the performance of a novel device conceived for measuring minute energy deposits in a low-density gas, capable of operating in various radiation fields, including in an accelerator environment. The ion-counting nanodosimeter provides a precise measurement of the ionization distribution deposited within a small wall-less gas volume, modeling nanometer-scales of condensed matter, e.g. the DNA molecule. We describe the instrument and its data acquisition system. The results of systematic studies with low-energy alpha particles, protons and carbon ions are compared to model simulations; they demonstrate the capabilities and indicate the limitations of this novel technique.

Evaluation of lesion clustering in irradiated plasmid DNA.

Purpose: To measure the yield of DNA strand breaks and clustered lesions in plasmid DNA irradiated with protons, helium nuclei, and γ-rays. Materials and methods: Plasmid DNA was irradiated with 1.03, 19.3 and 249 MeV protons (linear energy transfer = 25.5, 2.7, and 0.39 keV μm – 1 respectively), 26 MeV helium nuclei (25.5 keV μm) and γ-rays (137Cs or 60Co) in phosphate buffer containing 2 mM or 200 mM glycerol. Single-and double-strand breaks (SSB and DSB) were measured by gel electrophoresis, and clustered lesions containing base lesions were quantified by converting them into irreparable DSB in transformed bacteria. Results: For protons, SSB yield decreased with increasing LET (linear energy transfer). The yield of DSB and all clustered lesions seemed to reach a minimum around 3 keV μm – 1. There was a higher yield of SSB, DSB and total clustered lesions for protons compared to helium nuclei at 25.5 keV μm – 1. A difference in the yields between 137Cs and 60Co γ-rays was also observed, especially for SSB. Conclusion: In this work we have demonstrated the complex LET dependence of clustered-lesion yields, governed by interplay of the radical recombination and change in track structure. As expected, there was also a significant difference in clustered lesion yields between various radiation fields, having the same or similar LET values, but differing in nanometric track structure.

Water-equivalent path length calibration of a prototype proton CT scanner

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.