Table of contents

A dynamic phantom has been developed to allow for measurement of 3D cell survival distributions and the corresponding distributions of the RBE-weighted dose (RBED) in the presence of motion. The phantom consists of two 96-microwell plates holding Chinese hamster ovary cells inside a container filled with culture medium and is placed on a movable stage. Basic biological properties of the phantom were investigated without irradiation and after irradiation with a carbon ion beam, using both a stationary (reference) exposure and exposure during motion of the phantom perpendicular to the beam with beam tracking. There was no statistically significant difference between plating efficiency measured in the microwells with and without motion (0.75) and values reported in the literature. Mean differences between measured and calculated cell survival for these two irradiation modes were within ±5% of the target dose of 6 Gy (RBE).

Accurate real-time prediction of respiratory motion is desirable for effective motion management in radiotherapy for lung tumor targets. Recently, nonparametric methods have been developed and their efficacy in predicting one-dimensional respiratory-type motion has been demonstrated. To exploit the correlation among various coordinates of the moving target, it is natural to extend the 1D method to multidimensional processing. However, the amount of learning data required for such extension grows exponentially with the dimensionality of the problem, a phenomenon known as the 'curse of dimensionality'. In this study, we investigate a multidimensional prediction scheme based on kernel density estimation (KDE) in an augmented covariate–response space. To alleviate the 'curse of dimensionality', we explore the intrinsic lower dimensional manifold structure and utilize principal component analysis (PCA) to construct a proper low-dimensional feature space, where kernel density estimation is feasible with the limited training data. Interestingly, the construction of this lower dimensional representation reveals a useful decomposition of the variations in respiratory motion into the contribution from semiperiodic dynamics and that from the random noise, as it is only sensible to perform prediction with respect to the former. The dimension reduction idea proposed in this work is closely related to feature extraction used in machine learning, particularly support vector machines. This work points out a pathway in processing high-dimensional data with limited training instances, and this principle applies well beyond the problem of target-coordinate-based respiratory-based prediction. A natural extension is prediction based on image intensity directly, which we will investigate in the continuation of this work. We used 159 lung target motion traces obtained with a Synchrony respiratory tracking system. Prediction performance of the low-dimensional feature learning-based multidimensional prediction method was compared against the independent prediction method where prediction was conducted along each physical coordinate independently. Under fair setup conditions, the proposed method showed uniformly better performance, and reduced the case-wise 3D root mean squared prediction error by about 30–40%. The 90% percentile 3D error is reduced from 1.80 mm to 1.08 mm for 160 ms prediction, and 2.76 mm to 2.01 mm for 570 ms prediction. The proposed method demonstrates the most noticeable improvement in the tail of the error distribution.

The purpose of this study was to evaluate the performance of an algorithm used to measure the volumetric breast density (VBD) from digital mammograms. The algorithm is based on the calibration of the detector signal versus the thickness and composition of breast-equivalent phantoms. The baseline error in the density from the algorithm was found to be 1.25 ± 2.3% VBD units (PVBD) when tested against a set of calibration phantoms, of thicknesses 3–8 cm, with compositions equivalent to fibroglandular content (breast density) between 0% and 100% and under x-ray beams between 26 kVp and 32 kVp with a Rh/Rh anode/filter. The algorithm was also tested against images from a dedicated breast computed tomography (CT) scanner acquired on 26 volunteers. The CT images were segmented into regions representing adipose, fibroglandular and skin tissues, and then deformed using a finite-element algorithm to simulate the effects of compression in mammography. The mean volume, VBD and thickness of the compressed breast for these deformed images were respectively 558 cm³, 23.6% and 62 mm. The displaced CT images were then used to generate simulated digital mammograms, considering the effects of the polychromatic x-ray spectrum, the primary and scattered energy transmitted through the breast, the anti-scatter grid and the detector efficiency. The simulated mammograms were analyzed with the VBD algorithm and compared with the deformed CT volumes. With the Rh/Rh anode filter, the root mean square difference between the VBD from CT and from the algorithm was 2.6 PVBD, and a linear regression between the two gave a slope of 0.992 with an intercept of −1.4 PVBD and a correlation with R² = 0.963. The results with the Mo/Mo and Mo/Rh anode/filter were similar.

The purpose of this study is to test the hypothesis that gold nanoparticle (AuNP, nanogold)-enhanced radiation therapy (nanogold radiation therapy, NRT) is efficacious when treating the radiation resistant and highly aggressive mouse head and neck squamous cell carcinoma model, SCCVII, and to identify parameters influencing the efficacy of NRT. Subcutaneous (sc) SCCVII leg tumors in mice were irradiated with x-rays at the Brookhaven National Laboratory (BNL) National Synchrotron Light Source (NSLS) with and without prior intravenous (iv) administration of AuNPs. Variables studied included radiation dose, beam energy, temporal fractionation and hyperthermia. AuNP-mediated NRT was shown to be effective for the sc SCCVII model. AuNPs were more effective at 42 Gy than at 30 Gy (both at 68 keV median beam energy) compared to controls without gold. Similarly, at 157 keV median beam energy, 50.6 Gy NRT was more effective than 44 Gy NRT. At the same radiation dose (∼42 Gy), 68 keV was more effective than 157 keV. Hyperthermia and radiation therapy (RT) were synergistic and AuNPs enhanced this synergy, thereby further reducing TCD50 s (tumor control dose 50%) and increasing long-term survivals. It is concluded that gold nanoparticles enhance the radiation therapy of a radioresistant mouse squamous cell carcinoma. The data show that radiation dose, energy and hyperthermia influence efficacy and better define the potential utility of gold nanoparticles for cancer x-ray therapy.

We present a novel modified theory based upon Rayleigh scattering of ultrasound from composite nanoparticles with a liquid core and solid shell. We derive closed form solutions to the scattering cross-section and have applied this model to an ultrasound contrast agent consisting of a liquid-filled core (perfluorooctyl bromide, PFOB) encapsulated by a polymer shell (poly-caprolactone, PCL). Sensitivity analysis was performed to predict the dependence of the scattering cross-section upon material and dimensional parameters. A rapid increase in the scattering cross-section was achieved by increasing the compressibility of the core, validating the incorporation of high compressibility PFOB; the compressibility of the shell had little impact on the overall scattering cross-section although a more compressible shell is desirable. Changes in the density of the shell and the core result in predicted local minima in the scattering cross-section, approximately corresponding to the PFOB-PCL contrast agent considered; hence, incorporation of a lower shell density could potentially significantly improve the scattering cross-section. A 50% reduction in shell thickness relative to external radius increased the predicted scattering cross-section by 50%. Although it has often been considered that the shell has a negative effect on the echogeneity due to its low compressibility, we have shown that it can potentially play an important role in the echogeneity of the contrast agent. The challenge for the future is to identify suitable shell and core materials that meet the predicted characteristics in order to achieve optimal echogenity.

Monte Carlo simulation is the most accurate method for absorbed dose calculations in radiotherapy. Its efficiency still requires improvement for routine clinical applications, especially for online adaptive radiotherapy. In this paper, we report our recent development on a GPU-based Monte Carlo dose calculation code for coupled electron–photon transport. We have implemented the dose planning method (DPM) Monte Carlo dose calculation package (Sempau et al2000 Phys. Med. Biol.45 2263–91) on the GPU architecture under the CUDA platform. The implementation has been tested with respect to the original sequential DPM code on the CPU in phantoms with water–lung–water or water–bone–water slab geometry. A 20 MeV mono-energetic electron point source or a 6 MV photon point source is used in our validation. The results demonstrate adequate accuracy of our GPU implementation for both electron and photon beams in the radiotherapy energy range. Speed-up factors of about 5.0–6.6 times have been observed, using an NVIDIA Tesla C1060 GPU card against a 2.27 GHz Intel Xeon CPU processor.

Boundary element methods represent a valuable approach for designing gradient coils; these methods are based on meshing the current carrying surface into an array of boundary elements. The temporally varying magnetic fields produced by gradient coils induce electric currents in conducting tissues and so the exposure of human subjects to these magnetic fields has become a safety concern, especially with the increase in the strength of the field gradients used in magnetic resonance imaging. Here we present a boundary element method for the design of coils that minimize the electric field induced in prescribed conducting systems. This work also details some numerical examples of the application of this coil design method. The reduction of the electric field induced in a prescribed region inside the coils is also evaluated.

The purpose of the study is to evaluate the limiting velocity (LV) of a multileaf collimator and the leaf position in various collimator and gantry angles. Both leading leaves and trailing leaves began to move with a constant acceleration from 0 to 4 cm s⁻¹. When the beam hold occurred, the leaf velocity was defined as the leaf LV. Dynamic irradiation was performed at eight gantry angles of every 45° with three different collimator angles. The analysis of the LV and the leaf position was performed with a log file from a leaf motion controller. The mean LVs for Varian Clinac 21EX (21EX) ranged from 2.51 to 3.10 cm s⁻¹. The mean LVs for Clinac 600C ranged from 2.91 to 3.12 cm s⁻¹. When only central 5 mm leaves of 21EX moved, LVs were significantly higher than those when all 60 pairs of leaf moved, while the leaf position inconsistencies of the two accelerators were within 1 mm at the leaf velocities from 0.5 to 2.0 cm s⁻¹. It was recognized that the LV was affected by gravity. This measurement method can be utilized as routine quality assurance for a dynamic multileaf collimator (DMLC) is and easily reproducible.

To avoid potentially adverse health effects of electromagnetic fields (EMF), the International Commission on Non-Ionizing Radiation Protection (ICNIRP) has defined EMF reference levels from the basic restrictions on the induced whole-body-averaged specific absorption rate (SAR_wb) and the peak 10 g spatial-averaged SAR (SAR_10g). The objective of this study is to assess if the SAR in children remains below the basic restrictions upon exposure at the reference levels. Finite difference time domain (FDTD) modeling was used to calculate the SAR in six children and two adults when exposed to all 12 orthogonal plane wave configurations. A sensitivity study showed an expanded uncertainty of 53% (SAR_wb) and 58% (SAR_10g) due to variations in simulation settings and tissue properties. In this study, we found that the basic restriction on the SAR_wb is occasionally exceeded for children, up to a maximum of 45% in small children. The maximum SAR_10g values, usually found at body protrusions, remain under the limit for all scenarios studied. Our results are in good agreement with the literature, suggesting that the recommended ICNIRP reference levels may need fine tuning.

The use of hand-held ultrasound strain imaging for the intra-operative real-time visualization of HIFU (high-intensity focused ultrasound) ablations produced in the liver by a toroidal transducer was investigated. A linear 12 MHz ultrasound imaging probe was used to obtain radiofrequency signals. Using a fast cross-correlation algorithm, strain images were calculated and displayed at 60 frames s⁻¹, allowing the use of hand-held strain imaging intra-operatively. Fourteen HIFU lesions were produced in four pigs. Intra-operative strain imaging of HIFU ablations in the liver was feasible owing to the high frame rate. The correlation between dimensions measured on gross pathology and dimensions measured on B-mode images and on strain images were R = 0.72 and R = 0.94 respectively. The contrast between ablated and non-ablated tissue was significantly higher (p < 0.05) in the strain images (22 dB) than in the B-mode images (9 dB). Strain images allowed equivalent or improved definition of ablated regions when compared with B-mode images. Real-time intra-operative hand-held strain imaging seems to be a promising complement to conventional B-mode imaging for the guidance of HIFU ablations produced in the liver during an open procedure. These results support that hand-held strain imaging outperforms conventional B-mode ultrasound and could potentially be used for the assessment of thermal therapies.

This paper contains the recommendations of the high dose rate (HDR) brachytherapy working party of the UK Institute of Physics and Engineering in Medicine (IPEM). The recommendations consist of a Code of Practice (COP) for the UK for measuring the reference air kerma rate (RAKR) of HDR ¹⁹²Ir brachytherapy sources. In 2004, the National Physical Laboratory (NPL) commissioned a primary standard for the realization of RAKR of HDR ¹⁹²Ir brachytherapy sources. This has meant that it is now possible to calibrate ionization chambers directly traceable to an air kerma standard using an ¹⁹²Ir source (Sander and Nutbrown 2006 NPL Report DQL-RD 004 (Teddington: NPL) http://publications.npl.co.uk). In order to use the source specification in terms of either RAKR, (ICRU 1985 ICRU Report No 38 (Washington, DC: ICRU); ICRU 1997 ICRU Report No 58 (Bethesda, MD: ICRU)), or air kerma strength, S_K (Nath et al 1995 Med. Phys.22 209–34), it has been necessary to develop algorithms that can calculate the dose at any point around brachytherapy sources within the patient tissues. The AAPM TG-43 protocol (Nath et al 1995 Med. Phys.22 209–34) and the 2004 update TG-43U1 (Rivard et al 2004 Med. Phys.31 633–74) have been developed more fully than any other protocol and are widely used in commercial treatment planning systems. Since the TG-43 formalism uses the quantity air kerma strength, whereas this COP uses RAKR, a unit conversion from RAKR to air kerma strength was included in the appendix to this COP. It is recommended that the measured RAKR determined with a calibrated well chamber traceable to the NPL ¹⁹²Ir primary standard is used in the treatment planning system. The measurement uncertainty in the source calibration based on the system described in this COP has been reduced considerably compared to other methods based on interpolation techniques.

We have developed an image quality theory for filtered back-projection (FBP) and maximum likelihood expectation maximization (MLEM) based on quality measures like signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal and noise power spectra and the detective quantum efficiency (DQE) concept. Analytic expressions are derived for unattenuated SPECT reconstruction with ideal collimation to obtain the fundamental performance parameters of different reconstruction algorithms. This theory is verified by measurements of signal and noise power on simulated phantoms. We demonstrate that the noise power of reconstructed images is proportional to the diameter of the object given as a number of voxels. This is analytically proven for FBP and clarified by assessment of the convergence properties for MLEM. The latter technique is shown to be superior to FBP in terms of a noise level at least two times lower. The free choice of MLEM reconstruction parameters and correction for physical effects in the image acquisition enables quantitative evaluation of SPECT and PET images.

Fourier transform (FT)-based algorithms for magnetic resonance current density imaging (MRCDI) from one component of magnetic flux density have been developed for 2D and 3D problems. For 2D problems, where current is confined to the xy-plane and z-component of the magnetic flux density is measured also on the xy-plane inside the object, an iterative FT-MRCDI algorithm is developed by which both the current distribution inside the object and the z-component of the magnetic flux density on the xy-plane outside the object are reconstructed. The method is applied to simulated as well as actual data from phantoms. The effect of measurement error on the spatial resolution of the current density reconstruction is also investigated. For 3D objects an iterative FT-based algorithm is developed whereby the projected current is reconstructed on any slice using as data the Laplacian of the z-component of magnetic flux density measured for that slice. In an injected current MRCDI scenario, the current is not divergence free on the boundary of the object. The method developed in this study also handles this situation.

Ultrasound strain imaging is used to measure local tissue deformations. Usually, only strains along the ultrasound beam are estimated, because those estimates are most precise, due to the availability of phase information. For estimating strain in other directions we propose to steer the ultrasound beam at an angle, which allows estimating different projections of the 2D strain tensor, while phase information remains available. This study investigates beam steering at maximally three different angles to determine the full 2D strain tensor. The method was tested on simulated and experimental data of an inclusion phantom and a vessel phantom. The combination of data from a non-steered acquisition and acquisitions at a large positive and an equally large but negative steering angle enabled the most precise estimation of the strain components. The method outperforms conventional methods that do not use beam steering.

In this study we investigate the use of a new knowledge-based fuzzy logic technique to derive radiotherapy margins based on radiotherapy uncertainties and their radiobiological effects. The main radiotherapy uncertainties considered and used to build the model were delineation, set-up and organ motion-induced errors. The radiobiological effects of these combined errors, in terms of prostate tumour control probability and rectal normal tissue complication probability, were used to formulate the rule base and membership functions for a Sugeno type fuzzy system linking the error effect to the treatment margin. The defuzzified output was optimized by convolving it with a Gaussian convolution kernel to give a uniformly varying transfer function which was used to calculate the required treatment margins. The margin derived using the fuzzy technique showed good agreement compared to current prostate margins based on the commonly used margin formulation proposed by van Herk et al (2000 Int. J. Radiat. Oncol. Biol. Phys.47 1121–35), and has nonlinear variation above combined errors of 5 mm standard deviation. The derived margin is on average 0.5 mm bigger than currently used margins in the region of small treatment uncertainties where margin reduction would be applicable. The new margin was applied in an intensity modulated radiotherapy prostate treatment planning example where margin reduction and a dose escalation regime were implemented, and by inducing equivalent treatment uncertainties, the resulting target and organs at risk doses were found to compare well to results obtained using currently recommended margins.

The aim of this study was to investigate the dose response relationship of dicentrics in human lymphocytes after CT scans at tube voltages of 80 and 140 kV. Blood samples from a healthy donor placed in tissue equivalent abdomen phantoms of standard, pediatric and adipose sizes were exposed at dose levels up to 0.1 Gy using a 64-slice CT scanner. It was found that both the tube voltage and the phantom size significantly influenced the CT scan-induced linear dose–response relationship of dicentrics in human lymphocytes. Using the same phantom (standard abdomen), 80 kV CT x-rays were biologically more effective than 140 kV CT x-rays. However, it could also be determined that the applied phantom size had much more influence on the biological effectiveness. Obviously, the increasing slopes of the CT scan-induced dose response relationships of dicentrics in human lymphocytes obtained in a pediatric, a standard and an adipose abdomen have been induced by scattering effects of photons, which strongly increase with increasing phantom size.

Estimation of the cerebral metabolic rate of oxygen (CMRO₂) and cerebral blood flow (CBF) is important to investigate the neurovascular coupling and physiological components in blood oxygenation level-dependent (BOLD) signals quantitatively. Although there are methods that can determine CMRO₂ changes using functional MRI (fMRI) or near-infrared spectroscopy (NIRS), current approaches require a separate hypercapnia calibration process and have the potential to incur bias in many assumed model parameters. In this paper, a novel method to estimate CMRO₂ without hypercapnia is described using simultaneous measurements of NIRS and fMRI. Specifically, an optimization framework is proposed that minimizes the differences between the two forms of the relative CMRO₂–CBF coupling ratio from BOLD and NIRS biophysical models, from which hypercapnia calibration and model parameters are readily estimated. Based on the new methods, we found that group average CBF, CMRO₂, cerebral blood volume (CBV), and BOLD changes within activation of the primary motor cortex during a finger tapping task increased by 39.5 ± 21.4%, 18.4 ± 8.7%, 12.9 ± 6.7%, and 0.5 ± 0.2%, respectively. The group average estimated flow-metabolism coupling ratio was 2.38 ± 0.65 and the hypercapnia parameter was 7.7 ± 1.7%. These values are within the range of values reported from other literatures. Furthermore, the activation maps from CBF and CMRO₂ were well localized on the primary motor cortex, which is the main target region of the finger tapping task.

When delivering intensity-modulated radiation therapy (IMRT) using the volumetric modulated arc therapy (VMAT) technique on an Elekta accelerator equipped with the Elekta Beam Modulator multileaf collimator (MLC), the orientation of the MLC, relative to the accelerator head, is generally fixed during the delivery. However, it has the ability to rotate about its axis as the gantry simultaneously rotates. This note shows that this can confer a potential advantage when planning and delivering IMRT via VMAT. A computer model has been built in which the MLC rotation angle could be varied with each control point (gantry location) within the constraints of the specified MLC rotation speed and the time available for rotation. The model was used to optimize the orientation trajectory in such a way as to minimize the number of parked gaps between leaves which are needed for some gantry orientations but not for others (and which cannot reach the shielding safety of surrounding jaws in the time available). The presented work started with the simple situation of collimating gantry-successive single convex shapes. As a broad statement some 40% reduction in such parked gaps could be achieved. The study was then extended to investigate the optimized trajectories for multiple separate concave shapes with, once again, a saving in unwanted parked gaps or unwanted over-irradiation.

In treatment planning for ultrasound therapy, it is desirable to know the 3D structure of the ultrasound field. However, mapping an ultrasound field in 3D is very slow, with even a single planar raster scan taking typically several hours. Additionally, hydrophones that are used for field mapping are expensive and can be damaged in some therapy fields. So there is value in rapid methods which enable visualization and mapping of the ultrasound field in about 1 min. In this note we explore the feasibility of mapping the intensity distribution by measuring the temperature distribution produced in a thin sheet of absorbing material. A 0.2 mm thick acetate sheet forms a window in the wall of a water tank containing the transducer. The window is oriented at 45° to the beam axis, and the distance from the transducer to the window can be varied. The temperature distribution is measured with an infrared camera; thermal images of the inclined plane could be viewed in real time or images could be captured for later analysis and 3D field reconstruction. We conclude that infrared thermography can be used to gain qualitative information about ultrasound fields. Thermal images are easily visualized with good spatial and thermal resolutions (0.044 mm and 0.05 °C in our system). The focus and field structure such as side lobes can be identified in real time from the direct video output. 3D maps and image planes at arbitrary orientations to the beam axis can be obtained and reconstructed within a few minutes. In this note we are primarily interested in the technique for characterization of high intensity focused ultrasound (HIFU) fields, but other applications such as physiotherapy fields are also possible.

A radiotherapy treatment plan is based on an anatomical 'snapshot' of the patient acquired during the preparation stage using a kVCT (kilovolt computed tomography) scanner. Anatomical changes will occur during the treatment course, in some cases requiring a new treatment plan to deliver the prescribed dose. With the introduction of 3D volumetric on-board imaging devices, it became feasible to use the produced images for dose recalculation. However, the use of these on-board imaging devices in clinical routine for the calculation of dose depends on the stability of the images. In this study the validation of tomotherapy MVCT (megavolt computed tomography) produced images, for the purpose of dose recalculation by the Planned Adaptive software, has been performed. To investigate the validity of MVCT images for dose calculation, a treatment plan was created based on kVCT-acquired images of a solid water phantom. During a period of 4 months, MVCT images of the phantom have been acquired and were used by the planned adaptive software to recalculate the initial kVCT-based dose on the MVCT images. The influence of the adapted IVDTs (image value-to-density tables) has been investigated as well as the effect of image acquisition with or without preceding airscan. Output fluctuations and/or instabilities of the imaging beam result in MV images of different quality yielding different results when used for dose calculation. It was shown that the output of the imaging beam is not stable, leading to differences of nearly 3% between the original kV-based dose and the recalculated MV-based dose, for solid water only. MVCT images can be used for dose calculation purposes bearing in mind that the output beam is liable to fluctuations. The acquisition of an IVDT together with the MVCT image set, that is going to be used for dose calculation, is highly recommended.

This study examined the variation of dose–volume histogram (DVH) data sourced from multiple radiotherapy treatment planning systems (TPSs). Treatment plan exports were obtained from 33 Australian and New Zealand centres during a dosimetry study. Plan information, including DVH data, was exported from the TPS at each centre and reviewed in a digital review system (SWAN). The review system was then used to produce an independent calculation of DVH information for each delineated structure. The relationships between DVHs extracted from each TPS and independently calculated were examined, particularly in terms of the influence of CT scan slice and pixel widths, the resolution of dose calculation grids and the TPS manufacturer. Calculation of total volume and DVH data was consistent between SWAN and each TPS, with the small discrepancies found tending to increase with decreasing structure size. This was significantly influenced by the TPS model used to derive the data. For target structures covered with relatively uniform dose distributions, there was a significant difference between the minimum dose in each TPS-exported DVH and that calculated independently.