First proton radiography of an animal patient

The purpose of this work is to show the feasibility of proton radiography in terms of radiation dose, imaging speed, image quality (density and spatial resolution), and image content under clinical conditions. Protons with 214 MeV energy can penetrate through most patients and were used for imaging. The measured residual range (or energy) of the protons behind the patient was subtracted from the range without an object in the beam path and used to create a projected image. The image content is therefore proportional to the range that protons have lost in the patient. We took proton images of the head of a dog after it received proton radiotherapy treatment of a nasal tumor. The spatial resolution by measuring for each proton separately its coordinate in front of and behind the patient was approximately 1 mm. The acquisition time was on the order of several seconds and was limited by the patient table movement. The range sensitivity of the images was approximately 0.6 mm, which is good enough to use the images for therapy range verification. The dose that the dog received during exposure was 0.03 mGy, which is approximately a factor 50-100 smaller than for a comparable x-ray image. The potential to obtain quantitative images of proton ranges with satisfying spatial and range resolution and low dose to the patient suggests that proton radiography should be applied to patients who are under proton radiotherapy treatment.     

Proton-induced characteristic x-rays: a versatile source of ultrasoft x-rays for biological and biochemical investigations

Very low energy ( ultrasoft ) x-rays of 0.3-5 keV have provided a unique tool for investigation of mechanisms of radiation action, especially with respect to the energy and spatial properties of critical radiation damage in mammalian cells. Experimental investigations to date have been partially limited by the availability and characteristics of suitable ultrasoft x-ray sources. The suitability of small electrostatic proton accelerators, such as exist in many laboratories, have been investigated as a means of producing a secondary beam of ultrasoft x-rays suitable for irradiation of biological and biochemical systems. Results are presented on the physical characteristic of carbon K (0.28 keV) and aluminium K (1.5 keV) ultrasoft x-ray beams produced by bombardment of solid targets of carbon and aluminium with protons of energies up to 750 kV and currents up to 500 microA. These characteristics are compared with those of a cold cathode discharge ultrasoft x-ray tube previously used for mammalian cell investigations. It is seen that the proton accelerator produces much more versatile beams of characteristic ultrasoft x-rays which greatly extend the scope for future experiments on mammalian cells, micro-organisms and biochemical systems. Nevertheless there are situations in which the cold-cathode discharge tube will remain the source of choice and there are other situations, requiring for example energies between characteristic lines, where the greatly more complex synchrotron radiation sources are required.     

Density and spatial resolutions of proton radiography using a range modulation technique

The image quality of proton radiography using the method of beam energy modulation was studied to look into its practical uses. Two different depth-dose distributions generated by modulation were applied to investigate their effects on the density and spatial resolutions of the radiographic image. A steeper slope was found to provide higher resolution for the matching thickness of a phantom. The image was taken on a scintillation screen, and the distance between the phantom and the screen was a sensitive parameter on the resolution. For a beam with a range of 1.2 cm in Lucite, high-resolution images were attainable in the whole range. The resolution of proton images for different kinds of phantoms was examined in comparison with x-ray images as well as images simulated by a Monte Carlo code MCNPX. For a longer range of 18 cm, images attained by simulations indicated that density resolution is better maintained compared to spatial resolution, which is deteriorated by multiple Coulomb scattering.     

Characterizing the response of miniature scintillation detectors when irradiated with proton beams

Designing a plastic scintillation detector for proton radiation therapy requires careful consideration. Most of the plastic scintillators should not perturb a proton beam if they are sufficiently small but may exhibit some energy dependence due to the quenching effect. In this work, we studied the factors that would affect the performance of such scintillation detectors. We performed Monte Carlo simulations of proton beams with energies between 50 and 250 MeV to study signal amplitude, water equivalence, spatial resolution and quenching of light output. Implementation of the quenching effect in the Monte Carlo simulations was then compared with prior experimental data for validation. The signal amplitude of a plastic scintillating fiber detector was on the order of 300 photons per MeV of energy deposited in the detector, corresponding to a power of about 30 pW at a proton dose rate of 100 cGy min(-1). The signal amplitude could be increased by up to a factor of 2 with reflective coating. We also found that Cerenkov light was not a significant source of noise. Dose deposited in the plastic scintillator was within 2% of the dose deposited in a similar volume of water throughout the whole depth-dose curve for protons with energies higher than 50 MeV. A scintillation detector with a radius of 0.5 mm offers a sufficient spatial resolution for use with a proton beam of 100 MeV or more. The main disadvantage of plastic scintillators when irradiated by protons was the quenching effect, which reduced the amount of scintillation and resulted in dose underestimation by close to 30% at the Bragg peak for beams of 150 MeV or more. However, the level of quenching was nearly constant throughout the proximal half of the depth-dose curve for all proton energies considered. We therefore conclude that it is possible to construct an effective detector to overcome the problems traditionally encountered in proton dosimetry. Scintillation detectors could be used for surface or shallow measurements with a single calibration for specific beam energy. For deeper measurements, Monte Carlo simulations can be used to generate depth-dependent correction factors.     

Monochromatic minibeam radiotherapy: theoretical and experimental dosimetry for preclinical treatment plans

Monochromatic x-ray minibeam radiotherapy is a new radiosurgery approach based on arrays of submillimetric interlaced planar x-ray beams. The aim of this study was to characterize the dose distributions obtained with this new modality when being used for preclinical trials. Monte Carlo simulations were performed in water phantoms. Percentage depth-dose curves and dose profiles were computed for single incidences and interleaved incidences of 80 keV planar x-ray minibeam (0.6 × 5 mm) arrays. Peak to valley dose ratios were also computed at various depths for an increasing number of minibeams. 3D experimental polymer gel (nPAG) dosimetry measurements were performed using MRI devices designed for small animal imaging. These very high spatial resolution (50 μm) dose maps were compared to the simulations. Preclinical minibeams dose distributions were fully characterized. Experimental dosimetry correlated well with Monte Carlo calculations (Student t-tests: p > 0.1). F98 tumor-bearing rats were also irradiated with interleaved minibeams (80 keV, prescribed dose: 25 Gy). This associated preclinical trial serves as a proof of principle of the technique. The mean survival time of irradiated glioma-bearing rats increased significantly, when compared to the untreated animals (59.6 ± 2.8 days versus 28.25 ± 0.75 days, p < 0.001).     

Effect of x-ray energy dispersion in digital subtraction imaging at the iodine K-edge--a Monte Carlo study

The effect of the energy dispersion of a quasi-monochromatic x-ray beam on the performance of a dual-energy x-ray imaging system is studied by means of Monte Carlo simulations using MCNPX (Monte Carlo N-Particle eXtended) version 2.6.0. In particular, the case of subtraction imaging at the iodine K-edge, suitable for angiographic imaging application, is investigated. The average energies of the two beams bracketing the iodine K-edge are set to the values of 31.2 and 35.6 keV corresponding to the ones obtained with a compact source based on a conventional x-ray tube and a mosaic crystal monochromator. The energy dispersion of the two beams is varied between 0 and 10 keV of full width at half-maximum (FWHM). The signal and signal-to-noise ratio produced in the simulated images by iodine-filled cavities (simulating patient vessels) drilled in a PMMA phantom are studied as a function of the x-ray energy dispersion. The obtained results show that, for the considered energy separation of 4.4 keV, no dramatic deterioration of the image quality is observed with increasing x-ray energy dispersion up to a FWHM of about 2.35 keV. The case of different beam energies is also investigated by means of fast simulations of the phantom absorption.     

Nuclear scattering applied to radiography.

The possibility of using the nuclear scattering of 500-1000 MeV protons was investigated, in order to obtain direct, three-dimensional reconstruction of an object with only one exposure. The resolution should be about 1 mm3. Preliminary measurements with an incomplete set-up give a resolution of 10 mm3. Additional independent information on the relative concentration of hydrogen compared to other elements should also be obtainable by nuclear scattering radiography. The radiation doses involved are comparable to those of other techniques. The first experimental results are given.     

Radiation dose in diagnostic radiology: Monte Carlo simulation studies

We applied Monte Carlo calculations to determine the radiation dose absorbed in water phantoms. Monoenergetic incident x-ray beams with energies from 15 to 100 keV and phantom thicknesses from 5 to 20 cm were considered in this study. We calculated the spatial distributions of energy absorption in the phantom, the rad/R conversion factors, the average rad/R conversion factors, and the scatter-to-primary ratios of absorbed dose. We also compared the relative absorbed doses under various imaging conditions when the transmitted radiation produced a given optical density on radiographic film. The information provided will be useful for the estimation of radiation doses in various radiographic procedures.     

Prompt gamma imaging with a slit camera for real-time range control in proton therapy

Treatments delivered by proton therapy are affected by uncertainties on the range of the beam within the patient, requiring medical physicists to add safety margins on the penetration depth of the beam. To reduce these margins and deliver safer treatments, different projects are currently investigating real-time range control by imaging prompt gammas emitted along the proton tracks in the patient. This study reports on the feasibility, development and test of a new concept of prompt gamma camera using a slit collimator to obtain a one-dimensional projection of the beam path on a scintillation detector. This concept was optimized, using the Monte Carlo code MCNPX version 2.5.0, to select high energy photons correlated with the beam range and detect them with both high statistics and sufficient spatial resolution. To validate the Monte Carlo model, spectrometry measurements of secondary particles emitted by a PMMA target during proton irradiation at 160 MeV were realized. An excellent agreement with the simulations was observed when using subtraction methods to isolate the gammas in direct incidence. A first prototype slit camera using the HiCam gamma detector was consequently prepared and tested successfully at 100 and 160 MeV beam energies. Results confirmed the potential of this concept for real-time range monitoring with millimetre accuracy in pencil beam scanning mode for typical clinical conditions. If we neglect electronic dead times and rejection of detected events, the current solution with its collimator at 15 cm from the beam axis can achieve a 1-2 mm standard deviation on range estimation in a homogeneous PMMA target for numbers of protons that correspond to doses in water at the Bragg peak as low as 15 cGy at 100 MeV and 25 cGy at 160 MeV assuming pencil beams with a Gaussian profile of 5 mm sigma at target entrance.     

Effects of x-ray spectra on the DQE of a computed radiography system

The effect of incident x-ray beam quality on the measured detective quantum efficiency (DQE) of a computed radiography system was investigated. The incident x-ray beams used had peak tube potentials of 70, 95, and 120 kVp, were filtered with various thicknesses of a "patient equivalent phantom" (PEP), aluminum, and copper, and provided a consistent exposure to the storage phosphor. For each peak tube potential and filter combination, the one-dimensional modulation transfer function and noise power spectrum were measured and the square of the incident signal-to-noise ratio was estimated. The spatial frequency dependent DQE was calculated from these data. The DQE was integrated to provide an overall estimate of the efficiency and frequency response of the computed radiography system for the various x-ray beams. There was found to be a wide range of integral DQE (IDQE) values for the peak tube potential and filter combinations used. For example, the IDQE ranged from 3.0 to 0.9 mm(-2) using the peak tube potential and filter combinations 70 kVp with 5.1 cm PEP and 120 kVp with 30.3 cm PEP, respectively. Finally, peak tube potential and filter combinations 70 kVp with 10.2 cm PEP and 120 kVp with 20.2 cm PEP were chosen as standard x-ray beams that will be used at our facility to measure the DQE of digital radiographic imaging systems for evaluation and acceptance testing.     

Particle in cell simulation of laser-accelerated proton beams for radiation therapy

In this article we present the results of particle in cell (PIC) simulations of laser plasma interaction for proton acceleration for radiation therapy treatments. We show that under optimal interaction conditions protons can be accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The proton acceleration is due to the dragging Coulomb force arising from charge separation induced by the ponderomotive pressure (light pressure) of high-intensity laser. The proton energy and phase space distribution functions obtained from the PIC simulations are used in the calculations of dose distributions using the GEANT Monte Carlo simulation code. Because of the broad energy and angular spectra of the protons, a compact particle selection and beam collimation system will be needed to generate small beams of polyenergetic protons for intensity modulated proton therapy.     

Design and evaluation of an LSO PET detector for breast cancer imaging

Functional imaging with positron emission tomography (PET) may be a promising technique in conjunction with x-ray mammography for breast cancer patient management. Conventional whole body PET scanners provide metabolic images of breast cancer patients with several shortcomings related to the general-purpose nature of these systems. In whole body scanners, the detectors are typically 20-30 cm away from the breast or axilla, reducing sensitivity, and these scanners have relatively large detector elements (> 4 mm), limiting spatial resolution. Dedicated PET systems for breast imaging aim to overcome these limitations and improve the overall diagnostic quality of the images by bringing the detectors closer to the area to be imaged, thereby improving sensitivity, and by using smaller detector elements to improve the spatial resolution. We have designed and developed a modular PET detector that is composed of a 9x9 array of 3x3x20 mm3 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to an optical fiber taper, which in turn is coupled to a Hamamatsu R5900-C8 position-sensitive photomultiplier tube. These detectors can be tiled together without gaps to construct large area detector arrays to form a dedicated PET breast cancer imaging system. Two complete detector modules have been built and tested. All detector elements are clearly visualized upon flood irradiation of the module. The intrinsic spatial resolution (full-width at half-maximum) was measured to be 2.26 mm (range 1.8-2.6 mm). The average energy resolution was 19.5% (range 17%-24%) at 511 keV. The coincidence time resolution was measured to be 2.4 ns. The detector efficiency for 511 keV gamma rays was 53% using a 350 keV energy threshold. These promising results support the feasibility of developing a high resolution, high sensitivity dedicated PET scanner for breast cancer applications.     

Analytical linear energy transfer calculations for proton therapy

As the relative biological effectiveness of protons depends on the linear energy transfer (LET), simple methods for LET calculations are desired for the optimization of proton therapy. This work provides an analytical model for the LET on the central axis of broad proton beams in water, which can also be applied to spread-out Bragg peaks. For realistic treatment situations with polyenergetic beams, the LET is here defined as a local mean of the proton stopping power, weighted by the local energy spectrum. The proposed model considers only Coulomb interactions and neglects nonelastic nuclear interactions. By assuming a Gaussian shape for the energy spectrum and by using a suitable parametrization of the stopping power, analytical expressions for the track averaged and the dose averaged LET are derived, which account for range straggling as well as for the initial width of the energy spectrum. The analytical model was evaluated by Monte Carlo simulations with GEANT 3.21. Local energy spectra were simulated to obtain LET distributions for several cases, using clinical energies between 70 and 250 MeV and varying widths of the initial energy spectrum. Good agreement was found between the analytical model and the Monte Carlo simulations (with maximum deviations of 0.5 keV per micrometer), which justifies the assumptions used in the derivation of the analytical model.     

An analytical solution to proton Bragg peak deflection in a magnetic field

The role of MR imaging for image-guided radiation therapy (IGRT) is becoming more and more important thanks to the excellent soft tissue contrast offered by MRI. Hybrid therapy devices with integrated MRI scanners are under active development for x-ray therapy. The combination of proton therapy with MRI imaging has only been investigated at the theoretical or conceptual level. Of concern is the deflection of the proton beam in the homogeneous magnetic field. A previous publication has come to the conclusion that the impact of a 0.5 T magnetic field on the dose distribution for proton therapy is very small and lateral deflections stay well below 2?mm. The purpose of this study is to provide new insights into the effects of magnetic fields on a proton beam coming to rest in a patient. We performed an analytical calculation of the lateral deflection of protons with initial energies between 50 MeV and 250 MeV, perpendicular to the beam direction and the magnetic field. We used a power-law range-energy relationship and the Lorentz force in both relativistic and non-relativistic conditions. Calculations were done for protons coming to rest in water or soft tissue, and generalized to other uniform and non-uniform media. Results were verified by comparisons with numerical calculations and Monte Carlo simulations. A key result of our calculations is that the maximum lateral deflection at the end of range is proportional to the third power of the initial energy. Accordingly, due to the strong dependence on the energy, even a relatively small magnetic field of 0.5 T will cause a deflection of the proton beam by 1?cm at the end of range of a 200 MeV beam. The maximum deflection at 200 MeV is more than 10?times larger than that of a 90 MeV beam. Relativistic corrections of the deflection are generally small but they can become non-negligible at higher energies around 200 MeV and above. Contrary to previous findings, the lateral deflection of a proton beam can be significant (1?cm and above) even in relatively small magnetic fields of 0.5 T. However, the curved path of a proton beam in a magnetic field is easily predictable and it should be possible to account for this in treatment planning.     

The x-ray light valve: a low-cost digital radiographic imaging system

In recent years new digital x-ray radiographic and fluoroscopic systems based on large-area flat-panel technology have revolutionized our capability of producing x-ray images. However, such imagers are extraordinarily expensive and their rapid image acquisition capability is not required for many applications such as radiography. Here we report a novel approach to achieve a high-quality digital radiographic system at a cost which is only a small fraction of competitive digital technologies. The results demonstrate that our proposed x-ray light valve system has excellent spatial resolution and adequate sensitivity compared to existing technologies.     

Spatial resolution measurements in quasimonochromatic x rays with mosaic crystals for mammography application

A novel x-ray source for mammography application is being investigated. Quasimonochromatic x rays have been produced via Bragg diffraction with a W-anode x-ray tube and a graphite mosaic crystal array. The system provides 18 keV x rays with an energy resolution deltaE/E approximately equals 0.12. A thorough analysis of the spatial resolution of the system has been performed in order to understand and quantify the effect of the introduction of an active optical element such as a mosaic crystal in the x-ray path. The focal spot of the source and its emission properties have been studied by using the slit camera method. Experiments have shown that the introduction of a mosaic crystal in the optical path modifies the resolution properties of the Bragg diffraction-based radiography system. Along the direction perpendicular to the diffraction plane the resolution properties of the imaging system mainly depend on the x-ray tube focal spot size and position. Along the diffraction plane the focal spot size depends on mosaic characteristics and on the geometrical setup. Hence, it could be modified by setting the appropriate experimental conditions.     

Quasi-monochromatic x-rays for diagnostic radiology

Monochromatic x-ray beams are desirable in various fields of diagnostic radiology; in fact a reduction of the dose and an enhancement of the contrast could be achieved. In this work two different methods to monochromatize x-ray beams produced by conventional tubes have been compared. In the first one the beam is obtained via Bragg diffraction on mosaic crystal and in the second one by attenuating the polychromatic beam with aluminium filters. We have simulated quasi-monochromatic x-ray spectra by setting suitable values of Bragg's angle to obtain beams tuned to 20, 30, 40 and 50 keV with the SHADOW code, an x-ray tracing program designed to study the propagation and the interaction of a photon beam through an optical system. We have validated such a program by comparing some calculated data with measurements carried out on an experimental apparatus. Attenuated polychromatic x-ray spectra have been simulated by setting appropriate values of aluminium filters and potential with the SPECTRUM PROCESSOR, the software version of the Catalogue of Spectral Data for Diagnostic X-Rays, which provides radiographic x-ray spectra that can be attenuated with several material filters. The relation between the energy resolution and the flux as a function of the mean energy has been investigated and results have been compared. Results show that quasi-monochromatic x-ray beams produced via Bragg diffraction exhibit, for a given mean energy and energy resolution, a higher total flux compared to attenuated spectra.     

Particle selection for laser-accelerated proton therapy feasibility study

In this paper we present calculations for the design of a particle selection system for laser-accelerated proton therapy. Laser-accelerated protons coming from a thin high-density foil have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Our solution to this problem is a compact particle selection and collimation device that delivers small pencil beams of protons with desired energy spectra. We propose a spectrometer-like particle selection and beam modulation system in which the magnetic field will be used to spread the protons spatially according to their energies and emitting angles. Subsequently, an aperture will be used to select the protons within a therapeutic window of energy (energy modulation). It will be shown that for the effective proton spatial differentiation, the primary collimation device should be used, which will collimate protons to the desired angular distribution and limit the spatial mixing of different energy protons once they have traveled through the magnetic system. Due to the angular proton distribution, the spatial mixing of protons of different energies will always be present and it will result in a proton energy spread with the width depending on the energy. For 250 MeV protons, the width (from the maximum to the minimum energy) is found to be 50 MeV for the magnetic field configuration used in our calculations. As the proton energy decreases, its energy width decreases as well, and for 80 MeV protons it equals 9 MeV. The presence of the energy width in the proton energy distribution will modify the depth dose curves needed for the energy modulation calculation. The matching magnetic field setup will ensure the refocusing of the selected protons and the final beam will be collimated by the secondary collimator. The calculations presented in this article show that the dose rate that the selection system can yield is on the order of D=260 Gy/min for a field size of 1 x 1 cm2.     

Variations in dose response with x-ray energy of LiF:Mg,Cu,P thermoluminescence dosimeters: implications for clinical dosimetry

In many medical procedures where accurate radiation dose measurements are needed, the variation of detector response with x-ray energy is of concern. The response of LiF:Mg,Cu,P TLDs to a range of x-ray energies was analysed in monoenergetic (synchrotron), diagnostic and therapy radiation beams with the aim of implementing this dosimeter into clinical practice where existing dosimetry techniques are limited due to lack of sensitivity or tissue equivalence (e.g. neonatal radiography, mammography and brachytherapy). LiF:Mg,Cu,P TLDs in different forms from two manufacturers (MCP-N: TLD Poland, GR200: SDDML China) were irradiated using x-ray beams covering 10 keV to 18 MVp. Dose readings were compared with an ionization chamber. The effect of different TLD types and annealing cycles on clinical utility was investigated. The measured energy response of LiF:Mg,Cu,P TLDs was fit to a simple model devised by Kron et al (1998 Phys. Med. Biol. 43 3235-59) to describe the variation of TLD response with x-ray energy. If TLDs are handled as recommended in the present paper, the energy response of LiF:Mg,Cu,P deviates by a maximum of 15% from unity and agrees with the model to within 5% or experimental uncertainty between 15 keV and 10 MeV. LiF:Mg,Cu,P TLDs of all forms have consistent and superior energy response compared to the standard material LiF:Mg,Ti and are therefore suitable for a wide range of applications in diagnostic radiology and radiotherapy.     

A prototype of a quasi-monochromatic system for mammography applications

Improvement in image contrast and dose reduction, in mammographic x-ray imaging, can be achieved using narrow energy band x-ray beams in the 16-24 keV range. As part of an Italian Government funded project, a quasi-monochromatic system for mammography applications has been developed. The system is based on a tunable narrow energy band x-ray source operating in the 16-24 keV energy range. The bremsstrahlung beam is monochromatized via Bragg diffraction by a highly oriented pyrolytic graphite mosaic crystal (HOPG). The scanning system provides a large field (18 x 24 cm2) of quasi-monochromatic x-rays with energy resolution ranging from 10% at 18 keV to 17.2% at 24 keV. The system has been characterized in terms of fluence rate and energy resolution. An x-ray tube developed ad hoc allows us to acquire images in a reasonable time to minimize the motion blur. A qualitative analysis has been performed in order to know if the prototype system performances are far from a clinical application, by evaluating the spatial resolution, the field uniformity and the image quality as a function of the quasi-monochromatic beam energy. Dose evaluation has been performed as a function of the energy and compared to a conventional system for mammography. The quasi-monochromatic prototype system can produce comparable image quality at half the dose.