Radiotherapy Monte Carlo simulation using cloud computing technology.

Cloud computing allows for vast computational resources to be leveraged quickly and easily in bursts as and when required. Here we describe a technique that allows for Monte Carlo radiotherapy dose calculations to be performed using GEANT4 and executed in the cloud, with relative simulation cost and completion time evaluated as a function of machine count. As expected, simulation completion time decreases as 1/n for n parallel machines, and relative simulation cost is found to be optimal where n is a factor of the total simulation time in hours. Using the technique, we demonstrate the potential usefulness of cloud computing as a solution for rapid Monte Carlo simulation for radiotherapy dose calculation without the need for dedicated local computer hardware as a proof of principal.

A CAD interface for GEANT4.

Often CAD models already exist for parts of a geometry being simulated using GEANT4. Direct import of these CAD models into GEANT4 however, may not be possible and complex components may be difficult to define via other means. Solutions that allow for users to work around the limited support in the GEANT4 toolkit for loading predefined CAD geometries have been presented by others, however these solutions require intermediate file format conversion using commercial software. Here within we describe a technique that allows for CAD models to be directly loaded as geometry without the need for commercial software and intermediate file format conversion. Robustness of the interface was tested using a set of CAD models of various complexity; for the models used in testing, no import errors were reported and all geometry was found to be navigable by GEANT4.

The 25th anniversary of BUA for the assessment of osteoporosis: time for a new paradigm?

The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone at the calcaneus for the assessment of osteoporosis was first described within this journal 25 years ago. It was recognized in 2006 by Universities UK as being one of the '100 discoveries and developments in UK Universities that have changed the world' over the past 50 years. In 2008, the UK's Department of Health also recognized BUA assessment of osteoporosis in a publication highlighting 11 projects that have contributed to '60 years of NHS research benefiting patients'. The BUA technique has been extensively clinically validated and is utilized worldwide, with at least seven commercial systems currently providing calcaneal BUA measurement. However, there is still no fundamental understanding of the dependence of BUA upon the material and structural properties of cancellous bone. This review aims to provide an 'engineering in medicine' perspective and proposes a new paradigm based upon phase cancellation due to variation in propagation transit time across the receive transducer face to explain the non-linear relationship between BUA and bone volume fraction in cancellous bone.

A hybrid radiation detector for simultaneous spatial and temporal dosimetry.

In this feasibility study an organic plastic scintillator is calibrated against ionisation chamber measurements and then embedded in a polymer gel dosimeter to obtain a quasi-4D radiation detector. This hybrid dosimeter was irradiated with megavoltage x-rays from a linear accelerator, with temporal measurements of the dose rate being acquired by the scintillator and spatial measurements acquired with the gel dosimeter. The detectors employed in this study are radiologically equivalent; and we show that neither detector perturbs the intensity of the radiation field of the other. By employing these detectors in concert, spatial and temporal variations in the radiation intensity can now be detected and gel dosimeters can be calibrated for absolute dose from a single irradiation.

Modeling a complex micro-multileaf collimator using the standard BEAMnrc distribution.

PURPOSE: The component modules in the standard BEAMnrc istribution may appear to be insufficient to model micro-multileaf collimators that have trifaceted leaf ends and complex leaf profiles. This note indicates, however, that accurate Monte Carlo simulations of radiotherapy beams defined by a complex collimation device can be completed using BEAMnrc's standard VARMLC component module. METHODS: That this simple collimator model can produce spatially and dosimetrically accurate microcollimated fields is illustrated using comparisons with ion chamber and film measurements of the dose deposited by square and irregular fields incident on planar, homogeneous water phantoms. RESULTS: Monte Carlo dose calculations for on-axis and off-axis fields are shown to produce good agreement with experimental values, even on close examination of the penumbrae. CONCLUSIONS: The use of a VARMLC model of the micro-multileaf collimator, along with a commissioned model of the associated linear accelerator, is therefore recommended as an alternative to the development or use of in-house or third-party component modules for simulating stereotactic radiotherapy and radiosurgery treatments. Simulation parameters for the VARMLC model are provided which should allow other researchers to adapt and use this model to study clinical stereotactic radiotherapy treatments.

Generation of a 3D proximal femur shape from a single projection 2D radiographic image.

UNLABELLED: Generalized Procrustes analysis and thin plate splines were employed to create an average 3D shape template of the proximal femur that was warped to the size and shape of a single 2D radiographic image of a subject. Mean absolute depth errors are comparable with previous approaches utilising multiple 2D input projections. INTRODUCTION: Several approaches have been adopted to derive volumetric density (g cm(-3)) from a conventional 2D representation of areal bone mineral density (BMD, g cm(-2)). Such approaches have generally aimed at deriving an average depth across the areal projection rather than creating a formal 3D shape of the bone. METHODS: Generalized Procrustes analysis and thin plate splines were employed to create an average 3D shape template of the proximal femur that was subsequently warped to suit the size and shape of a single 2D radiographic image of a subject. CT scans of excised human femora, 18 and 24 scanned at pixel resolutions of 1.08 mm and 0.674 mm, respectively, were equally split into training (created 3D shape template) and test cohorts. RESULTS: The mean absolute depth errors of 3.4 mm and 1.73 mm, respectively, for the two CT pixel sizes are comparable with previous approaches based upon multiple 2D input projections. CONCLUSIONS: This technique has the potential to derive volumetric density from BMD and to facilitate 3D finite element analysis for prediction of the mechanical integrity of the proximal femur. It may further be applied to other anatomical bone sites such as the distal radius and lumbar spine.

Sensitivity of proximal femoral stiffness and areal bone mineral density to changes in bone geometry and density.

Areal bone mineral density (aBMD) is the most common surrogate measurement for assessing the bone strength of the proximal femur associated with osteoporosis. Additional factors, however, contribute to the overall strength of the proximal femur, primarily the anatomical geometry. Finite element analysis (FEA) is an effective and widely used computer-based simulation technique for modelling mechanical loading of various engineering structures, providing predictions of displacement and induced stress distribution due to the applied load. FEA is therefore inherently dependent upon both density and anatomical geometry. FEA may be performed on both three-dimensional and two-dimensional models of the proximal femur derived from radiographic images, from which the mechanical stiffness may be predicted. It is examined whether the outcome measures of two-dimensional FEA, two-dimensional, finite element analysis of X-ray images (FEXI), and three-dimensional FEA computed stiffness values of the proximal femur are more sensitive than aBMD to changes in trabecular bone density and femur geometry. It is assumed that if an outcome measure follows known trends with changes in density and geometric parameters, then an increased sensitivity will be indicative of an improved prediction of bone strength. All three outcome measures increased non-linearly with trabecular bone density, increased linearly with cortical shell thickness and neck width, decreased linearly with neck length, and were relatively insensitive to neck-shaft angle. For femoral head radius, aBMD was relatively insensitive, with two-dimensional FEXI and three-dimensional FEA demonstrating a non-linear increase and decrease in sensitivity respectively. For neck anteversion, aBMD decreased non-linearly, whereas both two-dimensional FEXI and three-dimensional FEA demonstrated a parabolic-type relationship, with the maximum stiffness being achieved at an angle of approximately 15 degrees. Multi-parameter analysis showed that all three outcome measures demonstrated their highest sensitivity to a change in cortical thickness. When changes in all input parameters were considered simultaneously, three and two-dimensional FEA had statistically equal sensitivities (0.41 +/- 0.20 and 0.42 +/- 0.16 respectively, p = ns) that were significantly higher than the sensitivity of aBMD (0.24 +/- 0.07; p = 0.014 and 0.002 for three-dimensional and two-dimensional FEA respectively). This simulation study suggests that since mechanical integrity and FEA are inherently dependent on anatomical geometry, FEXI stiffness, being derived from conventional two-dimensional radiographic images, may provide an improvement in the prediction of bone strength of the proximal femur than currently provided by aBMD.

Three dimensional stereolithography models of cancellous bone structures from muCT data: testing and validation of finite element results.

Stereolithography (STL) models of complex cancellous bone structures have been produced from three-dimensional micro-computed tomography data sets of human cancellous bone histological samples from four skeletal sites. The STL models have been mechanically tested and the derived stiffness compared with that predicted by finite element analysis. The results show a strong correlation (R2 = 0.941) between the predicted and calculated stiffnesses of the structures and show promise for the use of STL as an additional technique to complement the use of finite element models, for the assessment of the mechanical properties of complex cancellous bone structures.

Bulk evaluation and comparison of radiotherapy treatment plans for breast cancer.

This study provides a bulk, retrospective analysis of 151 breast and chest wall radiotherapy treatment plans, as a small-scale demonstration of the potential breadth and value of the information that may be obtained from clinical data mining. The treatments were planned at three centres belonging to one organisation over a period of 3 months. All 151 plans were used to evaluate inter-centre consistency and compliance with a local planning protocol. A subset of 79 plans, from one centre, were used in a more detailed evaluation of the effects of anatomical asymmetry on heart and lung dose, the effects of a metallic temporary tissue expander port on dose homogeneity and the overall conformity and homogeneity achieved in routine breast treatment planning. Differences in anatomical structure contouring and nomenclature were identified between the three centres, with all centres showing some non-compliance with the local planning protocol. When evaluated against standard conformity indices, these breast plans performed relatively poorly. However, when evaluated against recommended organ-at-risk tolerances, all evaluated plans performed sufficiently well that tighter planning tolerances could be recommended for future planning. Heart doses calculated in left breast and chest wall treatments were significantly higher than heart doses calculated in right sided breast and chest wall treatments (p < 0.001). In the treatment involving a temporary tissue expander, the inflated implant effectively pushed the targeted breast tissue away from the healthy tissues, leading to a dose distribution that was relatively conformal, although attenuation through the tissue expander's metallic port may have been underestimated by the treatment planning system. The results of this study exemplify the use of bulk treatment planning data to evaluate clinical workloads and inform ongoing treatment planning.

Comparison of active-set method deconvolution and matched-filtering for derivation of an ultrasound transit time spectrum.

The quality of ultrasound computed tomography imaging is primarily determined by the accuracy of ultrasound transit time measurement. A major problem in analysis is the overlap of signals making it difficult to detect the correct transit time. The current standard is to apply a matched-filtering approach to the input and output signals. This study compares the matched-filtering technique with active set deconvolution to derive a transit time spectrum from a coded excitation chirp signal and the measured output signal. The ultrasound wave travels in a direct and a reflected path to the receiver, resulting in an overlap in the recorded output signal. The matched-filtering and deconvolution techniques were applied to determine the transit times associated with the two signal paths. Both techniques were able to detect the two different transit times; while matched-filtering has a better accuracy (0.13 µs versus 0.18 µs standard deviations), deconvolution has a 3.5 times improved side-lobe to main-lobe ratio. A higher side-lobe suppression is important to further improve image fidelity. These results suggest that a future combination of both techniques would provide improved signal detection and hence improved image fidelity.

Field size consistency of nominally matched linacs.

Given that there is increasing recognition of the effect that sub-millimetre changes in collimator position can have on radiotherapy beam dosimetry, this study aimed to evaluate the potential variability in small field collimation that may exist between otherwise matched linacs. Field sizes and field output factors were measured using radiochromic film and an electron diode, for jaw- and MLC-collimated fields produced by eight dosimetrically matched Varian iX linacs (Varian Medical Systems, Palo Alto, USA). This study used nominal sizes from 0.6 × 0.6 to 10 × 10 cm(2), for jaw-collimated fields, and from 1 × 1 to 10 × 10 cm(2) for MLC-collimated fields, delivered from a zero (head up, beam directed vertically downward) gantry angle. Differences between the field sizes measured for the eight linacs exceeded the uncertainty of the film measurements and the repositioning uncertainty of the jaws and MLCs on one linac. The dimensions of fields defined by MLC leaves were more consistent between linacs, while also differing more from their nominal values than fields defined by orthogonal jaws. The field output factors measured for the different linacs generally increased with increasing measured field size for the nominal 0.6 × 0.6 to 1 × 1 cm(2) fields, and became consistent between linacs for nominal field sizes of 2 × 2 cm(2) and larger. The inclusion in radiotherapy treatment planning system beam data of small field output factors acquired in fields collimated by jaws (rather than the more-reproducible MLCs), associated with either the nominal or the measured field sizes, should be viewed with caution. The size and reproducibility of the fields (especially the small fields) used to acquire treatment planning data should be investigated thoroughly as part of the linac or planning system commissioning process. Further investigation of these issues, using different linac models, collimation systems and beam orientations, is recommended.

Clinical use of diodes and micro-chambers to obtain accurate small field output factor measurements.

There have been substantial advances in small field dosimetry techniques and technologies, over the last decade, which have dramatically improved the achievable accuracy of small field dose measurements. This educational note aims to help radiation oncology medical physicists to apply some of these advances in clinical practice. The evaluation of a set of small field output factors (total scatter factors) is used to exemplify a detailed measurement and simulation procedure and as a basis for discussing the possible effects of simplifying that procedure. Field output factors were measured with an unshielded diode and a micro-ionisation chamber, at the centre of a set of square fields defined by a micro-multileaf collimator. Nominal field sizes investigated ranged from 6 × 6 to 98 × 98 mm(2). Diode measurements in fields smaller than 30 mm across were corrected using response factors calculated using Monte Carlo simulations of the diode geometry and daisy-chained to match micro-chamber measurements at intermediate field sizes. Diode measurements in fields smaller than 15 mm across were repeated twelve times over three separate measurement sessions, to evaluate the reproducibility of the radiation field size and its correspondence with the nominal field size. The five readings that contributed to each measurement on each day varied by up to 0.26  %, for the "very small" fields smaller than 15 mm, and 0.18 % for the fields larger than 15 mm. The diode response factors calculated for the unshielded diode agreed with previously published results, within uncertainties. The measured dimensions of the very small fields differed by up to 0.3 mm, across the different measurement sessions, contributing an uncertainty of up to 1.2 % to the very small field output factors. The overall uncertainties in the field output factors were 1.8 % for the very small fields and 1.1 % for the fields larger than 15 mm across. Recommended steps for acquiring small field output factor measurements for use in radiotherapy treatment planning system beam configuration data are provided.

Examination of the properties of IMRT and VMAT beams and evaluation against pre-treatment quality assurance results.

This study aimed to provide a detailed evaluation and comparison of a range of modulated beam evaluation metrics, in terms of their correlation with QA testing results and their variation between treatment sites, for a large number of treatments. Ten metrics including the modulation index (MI), fluence map complexity, modulation complexity score (MCS), mean aperture displacement (MAD) and small aperture score (SAS) were evaluated for 546 beams from 122 intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment plans targeting the anus, rectum, endometrium, brain, head and neck and prostate. The calculated sets of metrics were evaluated in terms of their relationships to each other and their correlation with the results of electronic portal imaging based quality assurance (QA) evaluations of the treatment beams. Evaluation of the MI, MAD and SAS suggested that beams used in treatments of the anus, rectum, head and neck were more complex than the prostate and brain treatment beams. Seven of the ten beam complexity metrics were found to be strongly correlated with the results from QA testing of the IMRT beams (p < 0.00008). For example, values of SAS (with multileaf collimator apertures narrower than 10 mm defined as 'small') less than 0.2 also identified QA passing IMRT beams with 100% specificity. However, few of the metrics are correlated with the results from QA testing of the VMAT beams, whether they were evaluated as whole 360° arcs or as 60° sub-arcs. Select evaluation of beam complexity metrics (at least MI, MCS and SAS) is therefore recommended, as an intermediate step in the IMRT QA chain. Such evaluation may also be useful as a means of periodically reviewing VMAT planning or optimiser performance.

Biot theory: a review of its application to ultrasound propagation through cancellous bone.

To facilitate an understanding of the dependence of ultrasound velocity and attenuation upon the material and structural properties of cancellous bone, several theoretical concepts for ultrasound propagation have been adapted or developed, including the Biot theory and several scattering theories. Biot theory considers wave propagation through an elastic porous solid interspersed with fluid, considering the separate motion of the trabecular framework and morrow, respectively. The success achieved with the Biot theory has, to date, tended to be greater for the prediction of velocity than for attenuation. This article provides a review of the relevant literature, describing the physical parameters required for the Biot theory and their experimental determination. It is suggested that future developments should consider additional attenuation mechanisms, in particular, those due to scattering, local flow in microcracks, and surface roughness of the trabeculae.

The ability of ultrasound velocity to predict the stiffness of cancellous bone in vitro.

The mechanical status of bones is an important consideration in skeletal pathological conditions such as osteoporosis, which result in fracture at predominantly cancellous bone sites. Density is a good predictor of the stiffness and strength of cancellous bone. However, these mechanical properties are also dependent on the cancellous bone's architecture. The objective of this work was to investigate the ability of ultrasound velocity to predict the Young's modulus of elasticity of cancellous bone. The cancellous bone specimens were 20 mm cubes from bovine femur and 21 mm diameter mediolateral cylinders cored from human calcaneus. Ultrasound velocity (V) and Young's modulus (E) were determined in three orthogonal directions for the bovine cubes [anteroposterior (AP), mediolateral (ML), and proximodistal (PD)], and mediolaterally in the calcaneus. Apparent density (p) was determined after the other tests. Density alone explains 87.6% of the variance of Young's modulus in human calcaneal and bovine femoral bone tested in the PD direction only. Velocity, however, explains 95% and a combination of density and velocity 97%. Velocity and stiffness are not random with respect to the three directions in the bovine specimens. Further, for each cube we obtained the mean of the three values of E and of V, and characterized each value of E and V by their deviation from their mean. There is an extremely strong positive correlation (r = 0.80) showing that the degree of deviation is consistent for E and V, and of the same sign. These results demonstrate that the velocity of ultrasound in cubes of cancellous bone can give structure-specific information. In particular, knowledge of both density and velocity allows better predictions of stiffness than do density or ultrasound velocity on their own. Because there are noninvasive methods of measuring density that do not depend on ultrasonic measurement the combination of these two measurements promises, eventually, to give improved assessment of a bone's weakness and liability to fracture.

Prediction of mechanical properties of the human calcaneus by broadband ultrasonic attenuation.

Broadband ultrasonic attenuation (dB MHz cm-1, nBUA) was determined for specimens from 20 human calcanei, along with apparent density, elasticity (Young's modulus), and compressive strength. The calcanei were modified to provide "whole" (only soft tissue removed), "core" (mediolateral cores corresponding to in vivo measurement region), "can" (cortical end plates removed from core), and "def" (core defatted) samples. The nBUA values for the various modifications were highly correlated. The presence of the cortical endplates creates a significant nBUA, probably due to complex phase interactions. nBUAcan was a good predictor of elasticity (R2 = 75.7%) and strength (R2 = 73.6%). Apparent density was a better predictor of the mechanical variables than nBUA, with R2 values of 88.5% for elasticity and 87.6% for strength. The morphological anisotropy defined by "fabric" for the specimens was extremely uniform. The coefficient of variation in nBUA (40.5%) and compressive strength (64.4%) was significantly greater than for apparent density (23.5%) and fabric (6.7%). It is well known that a power law relationship exists between apparent density and elasticity or strength in cancellous bone. An interesting finding in this work is that there also appears to be a power law relationship between nBUA and apparent density, with an exponent of approximately 2, which, in the light of clinical implications, warrants further investigation.

Dynamic stochastic simulation of cancellous bone resorption.

A stochastic simulation of cancellous bone resorption was developed and applied to a simple two-dimensional lattice structure representing the vertebral body. The simulation is based upon the concept of a basic multicellular unit (BMU) where net resorption (-deltaB.BMU) is considered at bone/marrow surfaces. The cancellous bone structure is defined as a binary matrix with the size of the pixels corresponding to a square element of approximately 20 microm dimension. The simulation considers both the probability that any surface pixel will be activated into a BMU and, if activated, the length of the resorption cavity. The relationship between relative stiffness and density for the simulation was predicted by finite element analysis. The stochastic simulation was iterated eight times with the mechanical properties assessed after each stage. Perforation of a single trabeculae was first observed at step 2, the structure completely lacking connectivity and mechanical integrity by step 8. The slope of the stiffness-porosity graph was greater than unity for the first five steps, but thereafter approached zero because the structure had lost connectivity and effectively collapsed. The eight-step simulation was repeated five times and demonstrated that, although the stiffness/density relationships were similar at the extremes of density, the dependence of stiffness upon density varied. This clearly demonstrates the stochastic nature of the simulation upon cancellous bone structure, and is probably indicative of a significant dependence of mechanical integrity upon perforation effects.

Stochastically simulated assessment of anabolic treatment following varying degrees of cancellous bone resorption.

The aim of this study was to investigate the recovery in cancellous bone stiffness resulting from anabolic treatment following varying degrees of resorption, using a stochastic simulation applied to a simplistic structure consisting of five vertical and five horizontal trabeculae. The structure was initially resorbed, and "bone" elements were stochastically removed until nominal resorptions of 10%, 15%, 20%, 25%, and 30% were achieved. A stochastic simulation of anabolic treatment was then applied where bone elements were added, continuing until the original stiffness had been regained, for example, simulating treatment of a patient with an anabolic agent after a period of postmenopausal resorption. The resorption and anabolic simulations were repeated three times for each of the nominal resorptions. The stiffness of the bone structure decreased linearly with resorption, with a slope of approximately -2 and an R(2) of 97.0%; hence, the stiffness fell at approximately twice the rate of the reduction in density. When the various structures regained their original density, the resultant stiffness also had a linear relationship with the original resorption, with a slope of -1 and a lower R(2) of 86.1%. This implies that the reduction in stiffness, when original density was regained, fell proportionately with the degree of initial resorption and, therefore, after a resorption of 30%, when original density was regained, the stiffness of the resultant structure was approximately 30% less than that of the original structure. The density required for the original stiffness to be regained increased linearly with the degree of initial resorption, with a slope of approximately 0.5 and an R(2) of 65.2%, lower than that observed for the previous relationships. This indicates a greater spread of data and suggests greater variability in the formation phase beyond the point of regained original density. Because irreversible connectivity reduction is widely considered to be one of the earliest manifestations of estrogen loss, these findings, although obtained on a simulation of a simplistic cancellous bone structure, support the concept of early intervention to prevent potentially irreversible deterioration of trabecular architecture after menopause.

The non-linear relationship between BUA and porosity in cancellous bone.

There is growing interest in assessing the clinical value of ultrasound in the prediction and management of osteoporosis. However, the mechanism of ultrasound propagation in cancellous bone is not well understood. The Biot theory is one approach to modelling the interaction of sound waves with cancellous structure, and porosity is one of its input parameters. In this paper we report the relationship between broadband ultrasonic attenuation (BUA) corrected for specimen thickness (nBUA) and porosity in a porous Perspex cancellous bone mimic, a stereolithography cancellous bone mimic and in natural human and bovine tissue. nBUA and porosity have a non-linear parabolic relationship. The maximum nBUA value (nBUAmax) occurs at approximately 30% porosity in the Perspex mimic, approximately 70% in the stereolithography mimic and approximately 75% in natural cancellous bone. We discuss the effect of structure on the form of the nBUA-porosity relationship.

Fractal dimension predicts broadband ultrasound attenuation in stereolithography models of cancellous bone.

There has been considerable debate on the relative dependence of broadband ultrasound attenuation (nBUA, dB MHz(-1) cm(-1)) upon the density and structure of cancellous bone. A nonlinear relationship between nBUA and porosity has recently been demonstrated using stereolithography models, indicating a high structural dependence for nBUA. We report here on the measurement of trabecular perimeter and fractal dimension on the two-dimensional images used to create the stereolithography models. Adjusted coefficients of determination (R2) with nBUA were 94.4% (p < 0.0001) and 98.4% (p < 0.0001) for trabecular perimeter and fractal dimension respectively. The feature of fractal dimension representing both the porosity and connectivity of a given structure is most exciting. Further work is required to determine the relationship between broadband ultrasound attenuation and fractal dimension in complex three-dimensional cancellous bone structures.