Investigation of pulsed low dose rate radiotherapy using dynamic arc delivery techniques.

There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min⁻¹. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent cancers, which can be delivered using dynamic arc delivery techniques with ten full arcs and an effective dose rate of 6.7 ± 4.0 cGy min⁻¹.

The grid-walking test: assessment of sensorimotor deficits after moderate or severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and medial forebrain bundle.

The present study aims to evaluate the applicability of the grid-walking test in rats with moderate or severe dopamine-depletion incurred by unilateral nigro-striatal 6-hydroxydopamine (6-OHDA) lesions. Striatum samples were analyzed by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC) after behavioral testing. In Experiment 1, 2 weeks after the injection of 6-OHDA into the medial forebrain bundle, adult Wistar rats were divided into an l-3,4-dihydroxyphenylalanine (L-dopa) and a vehicle treatment group and their behaviors on the grid were compared. The severely lesioned animals (mean dopamine depletion of 92%) did not exhibit behavioral asymmetry in the number of contralateral foot-slips. However, L-dopa administration selectively reduced the number of foot-slips of the contralateral forelimb when compared with the vehicle group. In Experiment 2, 6-OHDA was injected into the dorsal striatum and foot-slips on the grid were analyzed 4, 9 and 13 days following the lesion. The rats with moderate dopamine-depletion (mean depletion of 54%) exhibited more contralateral forelimb-slips on all testing days. Compared with naive rats, hemiparkinsonian rats also showed more forelimb-slips. These results suggest that the grid-walking test should be a powerful and sensitive behavioral assay for sensory-motor deficits in rat models of nigro-striatal dopamine lesions.

A population-based study on incidence and economic burden of influenza-like illness in south China, 2007.

OBJECTIVES: The disease burden of influenza-like illness (ILI) in most tropical and subtropical countries has not been described adequately to date. The aim of this study was to determine the epidemiology and incidence of ILI, and to assess the economic burden in south China. STUDY DESIGN: Prospective study. METHODS: A population-based household survey was conducted quarterly in 2007 in Guangdong Province. RESULTS: The average number of subjects in each quarterly survey was 13,687. In total, 1002 cases of self-reported ILI were identified in all four surveys, indicating an annual incidence of 7.23 cases of ILI per 100 persons. The second quarter had the highest incidence of ILI (2.83 cases per 100 persons). Children aged 1-4 years, <1 year and 5-9 years had the highest annual incidence rates of ILI (49.87, 35.19 and 21.24 cases per 100 persons, respectively). The incidence of ILI was significantly higher in males than females (P < 0.001), and significantly higher in rural residents than urban residents (P < 0.001). The individual cost per episode of ILI represented approximately 20% of monthly per-capita income of residents. CONCLUSIONS: The results of this large-scale household study confirm that ILI places a substantial health and economic burden on south China. Ultimately, the results of this study will provide further information for understanding the disease burden of influenza in subtropical areas.

Advances in telemetric continuous intraocular pressure assessment.

With an ageing population showing an increasing prevalence of glaucoma, there is a pressing demand for continuous intraocular pressure (IOP) measurements which could surpass clinic-based measurements such as routine applanation tonometry. Glaucoma patients have fluctuations in IOP, and it has been proposed that these fluctuations are relevant to glaucoma progression. In addition, interindividual and intraindividual variation in corneal thickness and rigidity can lead to significant and poorly quantitated errors in applanation-based methods of estimating IOP. Microelectrical mechanical systems and complementary metal oxide semiconductor-based technology has enabled the development of smart miniaturised devices by augmenting the computational ability of microelectronics with capabilities of microsensors and microactuators. This review addresses various sensor technologies and both invasive and non-invasive approaches to the measurement of IOP. Advances in wireless communication (telemetry) between the implanted sensors and the external readout device are reviewed. In addition, biocompatibility of implantable sensors is discussed.

Ultra-thin TLDs for skin dose determination in high energy photon beams.

Estimation of surface dose is very important for patients undergoing radiation therapy. In this work we investigate the dose at the surface of a water phantom and at a depth of 0.007 cm, the practical reference depth for skin as recommended by ICRP and ICRU, with ultra-thin TLDs and Monte Carlo calculations. The calculations and measurements were carried out for fields ranging from 5 x 5 cm2 to 20 x 20 cm2 for 6 MV, 10 MV and 18 MV photon beams. The variation of the surface dose with angle of incidence and field size was investigated. Also, the exit dose was computed and measured for the same fields and angles of incidence. The dose at the ICRU reference depth was computed. Good agreement (+/-5%) was achieved between measurements and calculations. The surface dose at the entrance increased with the angle of incidence and/or the field size. The exit dose decreased with the angle of incidence but it increased with field size. The dose at the surface of the patient is mostly dependent on the beam energy, modality and beam obliquity rather than the field size and field separation. By correlating TLD measurements with Monte Carlo calculations, we were able to predict the dose at the skin surface with good accuracy. Knowing the dose received at the surface of the patient can lead to prediction of skin reactions helping with the design of new treatment techniques and alternative dose fractionation schemes.

Effect of statistical uncertainties on Monte Carlo treatment planning.

This paper reviews the effect of statistical uncertainties on radiotherapy treatment planning using Monte Carlo simulations. We discuss issues related to the statistical analysis of Monte Carlo dose calculations for realistic clinical beams using various variance reduction or time saving techniques. We discuss the effect of statistical uncertainties on dose prescription and monitor unit calculation for conventional treatment and intensity-modulated radiotherapy (IMRT) based on Monte Carlo simulations. We show the effect of statistical uncertainties on beamlet dose calculation and plan optimization for IMRT and other advanced treatment techniques such as modulated electron radiotherapy (MERT). We provide practical guidelines for the clinical implementation of Monte Carlo treatment planning and show realistic examples of Monte Carlo based IMRT and MERT plans.

A particle track-repeating algorithm for proton beam dose calculation.

A particle track-repeating algorithm has been developed for proton beam dose calculation for radiotherapy. Monoenergetic protons with 250 MeV kinetic energy were simulated in an infinite water phantom using the GEANT3 Monte Carlo code. The changes in location, angle and energy for every transport step and the energy deposition along the track were recorded for the primary protons and all secondary particles. When calculating dose for a patient with a realistic proton beam, the pre-generated particle tracks were repeated in the patient geometry consisting of air, soft tissue and bone. The medium and density for each dose scoring voxel in the patient geometry were derived from patient CT data. The starting point, at which a proton track was repeated, was determined according to the incident proton energy. Thus, any protons with kinetic energy less than 250 MeV can be simulated. Based on the direction of the incident proton, the tracks were first rotated and for the subsequent steps, the scattering angles were simply repeated for air and soft tissue but adjusted properly based on the scattering power for bone. The particle step lengths were adjusted based on the density for air and soft tissue and also on the stopping powers for bone while keeping the energy deposition unchanged in each step. The difference in nuclear interactions and secondary particle generation between water and these materials was ignored. The algorithm has been validated by comparing the dose distributions in uniform water and layered heterogeneous phantoms with those calculated using the GEANT3 code for 120, 150, 180 and 250 MeV proton beams. The differences between them were within 2%. The new algorithm was about 13 times faster than the GEANT3 Monte Carlo code for a uniform phantom geometry and over 700 times faster for a heterogeneous phantom geometry.

Modelling of electron contamination in clinical photon beams for Monte Carlo dose calculation.

The purpose of this work is to model electron contamination in clinical photon beams and to commission the source model using measured data for Monte Carlo treatment planning. In this work, a planar source is used to represent the contaminant electrons at a plane above the upper jaws. The source size depends on the dimensions of the field size at the isocentre. The energy spectra of the contaminant electrons are predetermined using Monte Carlo simulations for photon beams from different clinical accelerators. A 'random creep' method is employed to derive the weight of the electron contamination source by matching Monte Carlo calculated monoenergetic photon and electron percent depth-dose (PDD) curves with measured PDD curves. We have integrated this electron contamination source into a previously developed multiple source model and validated the model for photon beams from Siemens PRIMUS accelerators. The EGS4 based Monte Carlo user code BEAM and MCSIM were used for linac head sinulation and dose calculation. The Monte Carlo calculated dose distributions were compared with measured data. Our results showed good agreement (less than 2% or 2 mm) for 6, 10 and 18 MV photon beams.

Monitor unit calculation for Monte Carlo treatment planning.

In this work, we investigate a formalism for monitor unit (MU) calculation in Monte Carlo based treatment planning. By relating MU to dose measured under reference calibration conditions (central axis, depth of dose maximum in water, 10 cm x 10 cm field defined at 100 cm source-to-surface distance) our formalism determines the MU required for a treatment plan based on the prescription dose and Monte Carlo calculated dose distribution. Detailed descriptions and formulae are given for various clinical situations including conventional treatments and advanced techniques such as intensity-modulated radiotherapy (IMRT) and modulated electron radiotherapy (MERT). Analysis is made of the effects of source modelling, beam modifier simulation and patient dose calculation accuracy, all of which are important factors for absolute dose calculations using Monte Carlo simulations. We have tested the formalism through phantom measurements and the predicted MU values were consistent with measured values to within 2%. The formalism has been used for MU calculation and plan comparison for advanced treatment techniques such as MERT, extracranial stereotactic IMRT, MRI-based treatment planning and intensity-modulated laser-proton therapy studies. It is also used for absolute dose calculations using Monte Carlo simulations for treatment verification, which has become part of our comprehensive IMRT quality assurance programme.

Intensity modulated radiation therapy using laser-accelerated protons: a Monte Carlo dosimetric study.

In this paper we present Monte Carlo studies of intensity modulated radiation therapy using laser-accelerated proton beams. Laser-accelerated protons coming out of a solid high-density target have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Through the introduction of a spectrometer-like particle selection system that delivers small pencil beams of protons with desired energy spectra it is feasible to use laser-accelerated protons for intensity modulated radiotherapy. The method presented in this paper is a three-dimensional modulation in which the proton energy spectrum and intensity of each individual beamlet are modulated to yield a homogeneous dose in both the longitudinal and lateral directions. As an evaluation of the efficacy of this method, it has been applied to two prostate cases using a variety of beam arrangements. We have performed a comparison study between intensity modulated photon plans and those for laser-accelerated protons. For identical beam arrangements and the same optimization parameters, proton plans exhibit superior coverage of the target and sparing of neighbouring critical structures. Dose-volume histogram analysis of the resulting dose distributions shows up to 50% reduction of dose to the critical structures. As the number of fields is decreased, the proton modality exhibits a better preservation of the optimization requirements on the target and critical structures. It is shown that for a two-beam arrangement (parallel-opposed) it is possible to achieve both superior target coverage with 5% dose inhomogeneity within the target and excellent sparing of surrounding tissue.

A Monte Carlo dose calculation tool for radiotherapy treatment planning.

A Monte Carlo user code, MCDOSE, has been developed for radiotherapy treatment planning (RTP) dose calculations. MCDOSE is designed as a dose calculation module suitable for adaptation to host RTP systems. MCDOSE can be used for both conventional photon/electron beam calculation and intensity modulated radiotherapy (IMRT) treatment planning. MCDOSE uses a multiple-source model to reconstruct the treatment beam phase space. Based on Monte Carlo simulated or measured beam data acquired during commissioning, source-model parameters are adjusted through an automated procedure. Beam modifiers such as jaws, physical and dynamic wedges, compensators, blocks, electron cut-outs and bolus are simulated by MCDOSE together with a 3D rectilinear patient geometry model built from CT data. Dose distributions calculated using MCDOSE agreed well with those calculated by the EGS4/DOSXYZ code using different beam set-ups and beam modifiers. Heterogeneity correction factors for layered-lung or layered-bone phantoms as calculated by both codes were consistent with measured data to within 1%. The effect of energy cut-offs for particle transport was investigated. Variance reduction techniques were implemented in MCDOSE to achieve a speedup factor of 10-30 compared to DOSXYZ.

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.

Verification of IMRT dose distributions using a water beam imaging system.

A water beam imaging system (WBIS) has been developed and used to verify dose distributions for intensity modulated radiotherapy using dynamic multileaf collimator. This system consisted of a water container, a scintillator screen, a charge-coupled device camera, and a portable personal computer. The scintillation image was captured by the camera. The pixel value in this image indicated the dose value in the scintillation screen. Images of radiation fields of known spatial distributions were used to calibrate the device. The verification was performed by comparing the image acquired from the measurement with a dose distribution from the IMRT plan. Because of light scattering in the scintillator screen, the image was blurred. A correction for this was developed by recognizing that the blur function could be fitted to a multiple Gaussian. The blur function was computed using the measured image of a 10 cm x 10 cm x-ray beam and the result of the dose distribution calculated using the Monte Carlo method. Based on the blur function derived using this method, an iterative reconstruction algorithm was applied to recover the dose distribution for an IMRT plan from the measured WBIS image. The reconstructed dose distribution was compared with Monte Carlo simulation result. Reasonable agreement was obtained from the comparison. The proposed approach makes it possible to carry out a real-time comparison of the dose distribution in a transverse plane between the measurement and the reference when we do an IMRT dose verification.

Validation of a Monte Carlo dose calculation tool for radiotherapy treatment planning.

A new EGS4/PRESTA Monte Carlo user code, MCDOSE, has been developed as a routine dose calculation tool for radiotherapy treatment planning. It is suitable for both conventional and intensity modulated radiation therapy. Two important features of MCDOSE are the inclusion of beam modifiers in the patient simulation and the implementation of several variance reduction techniques. Before this tool can be used reliably for clinical dose calculation, it must be properly validated. The validation for beam modifiers has been performed by comparing the dose distributions calculated by MCDOSE and the well-benchmarked EGS4 user codes BEAM and DOSXYZ. Various beam modifiers were simulated. Good agreement in the dose distributions was observed. The differences in electron cutout factors between the results of MCDOSE and measurements were within 2%. The accuracy of MCDOSE with various variance reduction techniques was tested by comparing the dose distributions in different inhomogeneous phantoms with those calculated by DOSXYZ without variance reduction. The agreement was within 1.0%. Our results demonstrate that MCDOSE is accurate and efficient for routine dose calculation in radiotherapy treatment planning, with or without beam modifiers.

Monte Carlo verification of IMRT dose distributions from a commercial treatment planning optimization system.

The purpose of this work was to use Monte Carlo simulations to verify the accuracy of the dose distributions from a commercial treatment planning optimization system (Corvus, Nomos Corp., Sewickley, PA) for intensity-modulated radiotherapy (IMRT). A Monte Carlo treatment planning system has been implemented clinically to improve and verify the accuracy of radiotherapy dose calculations. Further modifications to the system were made to compute the dose in a patient for multiple fixed-gantry IMRT fields. The dose distributions in the experimental phantoms and in the patients were calculated and used to verify the optimized treatment plans generated by the Corvus system. The Monte Carlo calculated IMRT dose distributions agreed with the measurements to within 2% of the maximum dose for all the beam energies and field sizes for both the homogeneous and heterogeneous phantoms. The dose distributions predicted by the Corvus system, which employs a finite-size pencil beam (FSPB) algorithm, agreed with the Monte Carlo simulations and measurements to within 4% in a cylindrical water phantom with various hypothetical target shapes. Discrepancies of more than 5% (relative to the prescribed target dose) in the target region and over 20% in the critical structures were found in some IMRT patient calculations. The FSPB algorithm as implemented in the Corvus system is adequate for homogeneous phantoms (such as prostate) but may result in significant under or over-estimation of the dose in some cases involving heterogeneities such as the air-tissue, lung-tissue and tissue-bone interfaces.

Energy- and intensity-modulated electron beams for radiotherapy.

This work investigates the feasibility of optimizing energy- and intensity-modulated electron beams for radiation therapy. A multileaf collimator (MLC) specially designed for modulated electron radiotherapy (MERT) was investigated both experimentally and by Monte Carlo simulations. An inverse-planning system based on Monte Carlo dose calculations was developed to optimize electron beam energy and intensity to achieve dose conformity for target volumes near the surface. The results showed that an MLC with 5 mm leaf widths could produce complex field shapes for MERT. Electron intra- and inter-leaf leakage had negligible effects on the dose distributions delivered with the MLC, even at shallow depths. Focused leaf ends reduced the electron scattering contributions to the dose compared with straight leaf ends. As anticipated, moving the MLC position toward the patient surface reduced the penumbra significantly. There were significant differences in the beamlet distributions calculated by an analytic 3-D pencil beam algorithm and the Monte Carlo method. The Monte Carlo calculated beamlet distributions were essential to the accuracy of the MERT dose distribution in cases involving large air gaps, oblique incidence and heterogeneous treatment targets (at the tissue-bone and bone-lung interfaces). To demonstrate the potential of MERT for target dose coverage and normal tissue sparing for treatment of superficial targets, treatment plans for a hypothetical treatment were compared using photon beams and MERT.

Intraoperative echocardiography during congenital heart operations: experience from 1,000 cases.

BACKGROUND: This article provides an overview of the application of intraoperative echocardiography during repair of congenital heart defects based on our experience with 1,000 patients. METHODS: The patients in this study all underwent repair of a congenital heart defect between 1987 and 1994 at Duke University Medical Center. Echocardiography was performed on all patients in the operating room both before and after repair using epicardial or transesophageal imaging (or both). Hospital costs and outcome data were obtained for all patients. RESULTS: Overall, 44 patients (4.4%) underwent intraoperative revision of their repair based on echocardiographic findings. There was an initial learning phase during which 8.5% of repairs needed to be revised. With experience, the number of revisions fell to as low as 3% to 4%, but need for revision continued to occur throughout the series. Thirty-nine patients (88.6%) had a successful revision. It was not possible for the surgeon to predict the need for a revision based on his confidence in the repair: in 2.6% of patients thought by the surgeon to have a good repair, intraoperative echocardiography revealed the need for operative revision. The average cost for patients who return to the operating room during their hospitalization for revision of a repair is significantly greater than for those whose repairs are revised before they leave the operating room ($94,180.28 +/- $33,881.63 versus $21,415.79 +/- $8,215.74). There were no significant complication attributable to intraoperative echocardiography. CONCLUSIONS: In an era where complete repair of congenital heart defects is emphasized, intraoperative echocardiography provides information that can guide successful operative revision so that babies leave the operating room with optimal results.