Table of contents

Interstitial light delivery for therapeutic applications requires the use of fibre-based light diffusers. Such diffusers are presently manufactured to emit with a flat longitudinal power profile. Recently, diffusers with tailored longitudinal emission profiles have become available opening an avenue to improve conformal light delivery. This paper explores the ability of tailored diffusers to improve light dose confinement to the target volume. A formalism to calculate the light dose from an arbitrary source distribution is presented based on the convolution with an appropriate point source function. By choosing a source distribution corresponding to a cylindrical diffuser emitting with a sinusoidal profile, the set of attainable light dose distributions is characterized via a relationship between the diffuser's spatial frequency, the radial distance and the amplitude of the isodose contour.

The aim of this study was to investigate if microMOSFETs are suitable for the dosimetry and quality assurance of beta sources. The microMOSFET dosimeters have been tested for their angular dependence in a 6 MeV electron beam. The dose rate dependence was measured with an iridium-192 afterloading source. By varying the source-to-surface distance (SSD) in a 12 MeV electron beam the dose rate dependence in an electron beam was also investigated. To measure a depth dose curve the dose rate at 2, 5, 8 and 12 mm distance from the beta source train axis was determined with the OPTIDOS and the microMOSFET detector. A comparison between the two detector types shows that the microMOSFET is suitable for quality assurance of beta sources for endovascular brachytherapy (EVBT). The homogeneity of the source is checked by measurements at five points (for the 60 mm source at 10, 20, 30, 40 and 50 mm) along the source train. The microMOSFET was then used to evaluate the influence of a common stent type (single layer stainless steel) on the dose distribution in water. The stent led to a dose inhomogeneity of ±8.5%. Additionally the percentage depth dose curves with and without a stent were compared. The depth dose curves show good agreement which means that the stent does not change the beta spectrum significantly.

A multileaf collimator for electrons (eMLC) has been designed that fulfils the technical requirements for providing advanced irradiation techniques with electrons. In the present work, the basic design parameters of leaf material, leaf height, leaf width and number of leaves as well as leaf overtravel and leaf shape were determined such that an eMLC with motorized leaves can be manufactured by a company specialized in MLC technology. For this purpose, a manually driven eMLC with variable source-to-collimator distance (SCD) was used to evaluate the chosen leaf specification and investigate the impact of the SCD on the off-axis dose distribution. In order to select the final SCD of the eMLC, a compromise had to be found between maximum field size, minimum beam penumbra and necessary distance between eMLC and isocentre to eliminate patient realignments during gantry rotation. As a result, the eMLC is placed according to the target position at 72 and 84 cm SCD, respectively. This feature will be achieved by interchangeable distance holders. At these SCDs, the corresponding maximum field sizes at 100 cm source-to-isocentre distance are 20 × 20 cm and 17 × 17 cm, respectively. Finally, the off-axis dose distribution at the maximum opening of the eMLC was improved by fine-tuning the settings of the accelerator jaws and introducing trimmer bars above the eMLC. Following this optimization, a prototype eMLC consisting of 2 × 24 computer-controlled brass leaves is manufactured by 3D Line Medical Systems.

fMRI-constrained EEG/MEG source imaging can be a powerful tool in studying human brain functions with enhanced spatial and temporal resolutions. Recent studies on the combination of fMRI and EEG/MEG have suggested that fMRI prior information could be readily implemented by simply imposing different weighting factors to cortical sources overlapping with the fMRI activations. It has been also reported, however, that such a hard constraint may cause severe distortions or elimination of meaningful EEG/MEG sources when there are distinct mismatches between the fMRI activations and the EEG/MEG sources. If one wants to obtain the actual EEG/MEG source locations and uses the fMRI prior information as just an auxiliary tool to enhance focality of the distributed EEG/MEG sources, it is reasonable to weaken the strength of fMRI constraint when severe mismatches between fMRI and EEG/MEG sources are observed. The present study suggests an efficient technique to automatically adjust the strength of fMRI constraint according to the mismatch level. The use of the proposed technique rarely affects the results of conventional fMRI-constrained EEG/MEG source imaging if no major mismatch between the two modalities is detected; while the new results become similar to those of typical EEG/MEG source imaging without fMRI constraint if the mismatch level is significant. A preliminary simulation study using realistic EEG signals demonstrated that the proposed technique can be a promising tool to selectively apply fMRI prior information to EEG/MEG source imaging.

We develop and demonstrate improved image-forming optics for optical projection tomography (OPT), with which the parallel integral throughout an object can be obtained. This method results in an improved resolution for OPT images, especially for the cross sections far from the optical axis of the image-forming optics. We find the optimal configuration used in our OPT system by use of a point spread function and simulation technique. The new method is validated by both numerical simulations and experimental results. The spatial resolution of the OPT system presented is ∼40 µm.

The advantages and limitations of using partial differential analysis to assess the methodological uncertainty associated with the measurement of the dielectric properties of a material are discussed and an alternative pragmatic approach is proposed. It relies on repeat measurements of the dielectric properties of reference liquids and an analysis to estimate random and systematic uncertainties. Examples of measurement uncertainty are provided for well-defined monomolecular materials and for less homogeneous materials at microwave frequencies. All examples relate to measurement with an open-ended coaxial probe but the methodology is not specific to this technique. Examination of the components of uncertainty in the dielectric properties of biological tissue shows that, where the system is free of methodological bias, random fluctuations originating from sampling and natural inhomogeneity dominate the uncertainty budget. In such cases, the mean value of the measured parameter and the standard error of the mean can be taken as a good measure of the true value and its associated uncertainty.

Microvascular injury is recognized as a major tissue damage mechanism of ablative cryosurgery. Endothelial cells lining the vessel wall are thought to be the initial target of freezing. However, details of this injury mechanism are not yet completely understood. In this study, ECMatrix™ 625 was used to mimic the tumour environment and to allow the endothelial cells cultured in vitro to form the tube-like structure of the vasculature. The influence of water dehydration on the integrity of this structure was investigated. It was found that the initial cell shape change was mainly controlled by water dehydration, dependent on the cooling rate, resulting in the shrinkage of cells in the direction normal to the free surface. As the cooling was prolonged and temperature was lowered, further cell shape change could be induced by the chilling effects on intracellular proteins, and focal adhesions to the basement membrane. Quantitative analysis showed that the freezing induced dehydration greatly enhanced the cell surface stresses, especially in the axial direction. This could be one of the major causes of the final breaking of the cell junction and cell detachment.

Respiratory research with mice using micro-computed tomography (micro-CT) has been predominantly hindered by the limited resolution and signal-to-noise ratio (SNR) as a result of respiratory motion artefacts. In this study, we develop a novel technique for capturing the lung microstructure in vivo using micro-CT, through a computer-controlled intermittent iso-pressure breath hold (IIBH), to reduce respiratory motion, increasing resolution and SNR of reconstructed images. We compare four gating techniques, i.e. no gating, late expiratory (LE) gating, late inspiratory (LI) gating and finally intermittent iso-pressure breath hold (IIBH) gating. Quantitatively, we compare several common image analysis methods used to extract valuable physiologic and anatomic information from the respiratory system, and show that the IIBH technique produces the most representative and repeatable results.

The metal oxide semiconductor field-effect transistor (MOSFET) dosimeter has been widely studied for use as a dosimeter for patient dose verification. The major advantage of this detector is its size, which acts as a point dosimeter, and also its ease of use. The commercially available TN502RD MOSFET dosimeter manufactured by Thomson and Nielsen has never been used for proton dosimetry. Therefore we used the MOSFET dosimeter for the first time in proton dose measurements. In this study, the MOSFET dosimeter was irradiated with 190 MeV therapeutic proton beams. We experimentally evaluated dose reproducibility, linearity, fading effect, beam intensity dependence and angular dependence for the proton beam. Furthermore, the Bragg curve and spread-out Bragg peak were also measured and the linear-energy transfer (LET) dependence of the MOSFET response was investigated. Many characteristics of the MOSFET response for proton beams were the same as those for photon beams reported in previous papers. However, the angular MOSFET responses at 45, 90, 135, 225, 270 and 315 degrees for proton beams were over-responses of about 15%, and moreover the MOSFET response depended strongly on the LET of the proton beam. This study showed that the angular dependence and LET dependence of the MOSFET response must be considered very carefully for quantitative proton dose evaluations.

A new nanodosimetry-based linear-quadratic (LQ) model of cell survival for mixed-LET radiations has been developed. The new model employs three physical quantities and three biological quantities. The three physical quantities are related to energy depositions at two nanometre scales, 5 nm and 25 nm. The three biological quantities are related to the lesion production and interaction probabilities and the lesion repair rate. The coefficients α and β of the LQ formula (αD + βD²) are explicitly expressed in terms of the three physical quantities and the three biological quantities. The new model is shown to be consistent with the previously published cell survival curves of V-79 cells. The advantage of this new model is that it can be conveniently adopted to estimate the iso-effect for radiotherapies that involve ionizing radiation of mixed LET. An example is given to estimate the cell survival fractions for a high-dose-rate mixed neutron and gamma-ray field from a ²⁵²Cf source.

Depth distributions of positron-emitting nuclei in PMMA phantoms are calculated within a Monte Carlo model for heavy-ion therapy (MCHIT) based on the GEANT4 toolkit (version 8.0). The calculated total production rates of ¹¹C, ¹⁰C and ¹⁵O nuclei are compared with experimental data and with corresponding results of the FLUKA and POSGEN codes. The distributions of e⁺ annihilation points are obtained by simulating radioactive decay of unstable nuclei and transporting positrons in the surrounding medium. A finite spatial resolution of the positron emission tomography (PET) is taken into account in a simplified way. Depth distributions of β⁺-activity as seen by a PET scanner are calculated and compared to available data for PMMA phantoms. The obtained β⁺-activity profiles are in good agreement with PET data for proton and ¹²C beams at energies suitable for particle therapy. The MCHIT capability to predict the β⁺-activity and dose distributions in tissue-like materials of different chemical composition is demonstrated.

For more information on this article, see medicalphysicsweb.org

The authors have been investigating metrics of extremely low frequency magnetic field exposure under different circumstances. In this paper, we describe the properties of magnetic fields in homes, in the vicinity of powerlines, on trains and from a library security system. We conclude that there are key differences between each of these fields. This suggests that there may be a characterizable pattern for magnetic fields in different situations.

The effect of covariance between the Kα and Kβ lead peak concentrations on the uncertainty in the ¹⁰⁹Cd K x-ray fluorescence measurement of lead in bone is addressed here. It is commonly believed that this covariance arises as a result of the mutual dependence of the ratios of x-ray to coherent amplitudes on the same coherent peak amplitude. Previous work assumes statistical independence between spectral quantities of interest, crudely estimates the uncertainties in the lead peak concentrations, and suggests that the effect of covariance on the measurement uncertainty is small and can be ignored. Consequently, the current method followed by most laboratories reports the measurement uncertainty as if the fluctuations in the measured peak concentrations were independent. The robustness of such assumption, however, is undermined by existing epidemiological data. This paper assesses the magnitude of the covariance effect, using a method based on the observed significant correlations between the ratios of x-ray to coherent peak amplitudes in series of repeat phantom measurements. The revised uncertainties following this approach can exceed the uncertainties estimated by the accepted method by as much as 40%, which suggests a much stronger effect of covariance on the measurement uncertainty than previously reported.

In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

In SPECT, simultaneous ^99mTc/¹²³I acquisitions allow comparison of the distribution of two radiotracers in the same physiological state, without any image misregistration, but images can be severely distorted due to cross-talk between the two isotopes. We propose a generalized spectral factor analysis (GSFA) method for solving the cross-talk issue in simultaneous ^99mTc/¹²³I SPECT. In GSFA, the energy spectrum of the photons in any pixel is expressed as a linear combination of five common spectra: ^99mTc and ¹²³I photopeaks and three scatter spectra. These basis spectra are estimated from a factor analysis of all spectra using physical priors (e.g. Klein–Nishina distributions). GSFA was evaluated on ^99mTc/¹²³I Monte Carlo simulated data and compared to images obtained using recommended spectral windows (WIN) and to the gold standard (GS) images (scatter-free, cross-talk-free and noise-free). Using GSFA, activity concentration differed by less than 9% compared to GS values against differences from −23% to 110% with WIN in the ¹²³I and ^99mTc images respectively. Using GSFA, simultaneous ^99mTc/¹²³I imaging can yield images of similar quantitative accuracy as when using sequential and scatter-free ^99mTc/¹²³I imaging in brain SPECT.

In studying bioelectromagnetic problems, finite element analysis (FEA) offers several advantages over conventional methods such as the boundary element method. It allows truly volumetric analysis and incorporation of material properties such as anisotropic conductivity. For FEA, mesh generation is the first critical requirement and there exist many different approaches. However, conventional approaches offered by commercial packages and various algorithms do not generate content-adaptive meshes (cMeshes), resulting in numerous nodes and elements in modelling the conducting domain, and thereby increasing computational load and demand. In this work, we present efficient content-adaptive mesh generation schemes for complex biological volumes of MR images. The presented methodology is fully automatic and generates FE meshes that are adaptive to the geometrical contents of MR images, allowing optimal representation of conducting domain for FEA. We have also evaluated the effect of cMeshes on FEA in three dimensions by comparing the forward solutions from various cMesh head models to the solutions from the reference FE head model in which fine and equidistant FEs constitute the model. The results show that there is a significant gain in computation time with minor loss in numerical accuracy. We believe that cMeshes should be useful in the FEA of bioelectromagnetic problems.

Techniques for quantitative magnetic resonance imaging (MRI) have been developed for non-invasive estimation of the mineral density and structure of trabecular bone. The R*₂ relaxation rate (i.e. 1/T*₂) is sensitive to bone mineral density (BMD) via susceptibility differences between trabeculae and bone marrow, and by binarizing MRI images, structural variables, such as apparent bone volume fraction, can be assessed. In the present study, trabecular bone samples of human patellae were investigated in vitro at 1.5 T to determine the ability of MRI-derived variables (R*₂ and bone volume fraction) to predict the mechanical properties (Young's modulus, yield stress and ultimate strength). Further, the MRI variables were correlated with reference measurements of volumetric BMD and bone area fraction as determined with a clinical pQCT system. The MRI variables correlated significantly (p < 0.01) with the mechanical variables (r = 0.32–0.46), BMD (r = 0.56) and bone structure (r = 0.51). A combination of R*₂ and MRI-derived bone volume fraction further improved the prediction of yield stress and ultimate strength. Although pQCT showed a trend towards better prediction of the mechanical properties, current results demonstrate the feasibility of combined MR imaging of marrow susceptibility and bone volume fraction in predicting the mechanical strength of trabecular bone and bone mineral density.

To replace the conventional pinhole (normal cone-beam) collimator, a novel skew-slit collimator was previously proposed and a Novikov-type algorithm developed to reconstruct images using the skew-slit geometry. The goal of this paper is to develop a reconstruction algorithm that has better noise control than the Novikov-type algorithm. The new algorithm is able to compensate for uniform attenuation, and computer simulation results show that reconstructed images are less noisy.

We calculate the induced electric stress forces on transient hydrophobic pores in the membrane of an erythrocyte exposed to an electric field. For this purpose, we use a finite element numerical technique and a realistic shape for the biconcave erythrocyte represented by a set of parametric equations in terms of Jacobi elliptic functions. The results clearly show that the electrical forces on the base and sidewalls of the pore favour the opening of the pore. A comparison of the force densities obtained for an unstretched flat membrane and for the realistic erythrocyte model shows that the thinning and curvature of the membrane cannot be neglected. We also show that the pore deformation depends strongly on the orientation of the pore with respect to the external field, and in particular is very small when the field is tangent to the membrane surface

In this paper is investigated the use of the scan statistic for evaluating the detectability of small nodules in medical images. The scan-statistic method is often used in applications in which random fields must be searched for abnormal local features. Several results of the detection with localization theory are reviewed and a generalization is presented using the noise nodule distribution obtained by scanning arbitrary areas. One benefit of the noise nodule model is that it enables determination of the scan-statistic distribution by using only a few image samples in a way suitable both for simulation and experimental setups. Also, based on the noise nodule model, the case of multiple targets per image is addressed and an image abnormality test using the likelihood ratio and an alternative test using multiple decision thresholds are derived. The results obtained reveal that in the case of low contrast nodules or multiple nodules the usual test strategy based on a single decision threshold underperforms compared with the alternative tests. That is a consequence of the fact that not only the contrast or the size, but also the number of suspicious nodules is a clue indicating the image abnormality. In the case of the likelihood ratio test, the multiple clues are unified in a single decision variable. Other tests that process multiple clues differently do not necessarily produce a unique ROC curve, as shown in examples using a test involving two decision thresholds. We present examples with two-dimensional time-of-flight (TOF) and non-TOF PET image sets analysed using the scan statistic for different search areas, as well as the fixed position observer.

Experimental data from 593 photon beams were used to quantify the errors in dose calculations using a previously published pencil kernel model. A correction of the kernel was derived in order to remove the observed systematic errors. The remaining residual error for individual beams was modelled through uncertainty associated with the kernel model. The methods were tested against an independent set of measurements. No significant systematic error was observed in the calculations using the derived correction of the kernel and the remaining random errors were found to be adequately predicted by the proposed method.

Gafchromic^® XR-R films are a useful tool to evaluate entrance skin dose in interventional radiology. Another dosimetric quantity of interest in diagnostic and interventional radiology is the dose area product (DAP). In this study, a method to evaluate DAP using Gafchromic^® XR-R films and a flat-bed scanner was developed and tested. Film samples were exposed to an x-ray beam of 80 kVp over a dose range of 0–10 Gy. DAP measurements with films were obtained from the digitalization of a film sample positioned over the x-ray beam window during the exposure. DAP values obtained with this method were compared for 23 cardiological interventional procedures with DAP values displayed by the equipment. The overall one-sigma dose measurement uncertainty depended on the absorbed dose, with values below 6% for doses above 1 Gy. A maximum discrepancy of 16% was found, which is of the order of the differences in the DAP measurements that may occur with different calibration procedures. Based on the results presented, after an accurate calibration procedure and a thorough inspection of the relationship between the actual dose and the direct measured quantity (net optical density or net pixel value variation), Gafchromic^® XR-R films can be used to assess the DAP.

The purpose of this work was to investigate the dependence of whole-body averaged specific energy absorption rate (SAR), calculated using the finite-difference time-domain (FDTD) method, on the width of the free space region between a numerical phantom and the perfectly matched layer (pml) absorbing boundary. Results show that an increase in this width from 2 cells to 70 cells caused variations in the calculated whole-body averaged SAR of less than 2% for the FDTD code employing split-field pmls. Similarly, an increase in the width of the pml layer had little effect on the whole-body SAR values.

SIRAD badge dosimeters are a new type of personal dosimeter designed to measure radiation exposure up to 200 R and give a visual qualitative measurement of exposure. This is performed using the active dosimeter window, which contains a radiochromic material amalgamated in the badge assembly. When irradiated, the badges active window turns blue, which can be matched against the given colour chart for a qualitative assessment of the exposure received. Measurements have been performed to analyse the absorption spectra of the active window, and results show that the window automatically turns a blue colour upon irradiation and produces two peaks in the absorption spectra located at 617 nm and 567 nm. When analysed with a common computer desktop scanner, the optical density response of the film to radiation exposure is non-linear but reproducible. The net OD of the film was 0.21 at 50 R exposure and 0.31 at 200 R exposure when irradiated with a 6 MV x-ray energy beam. When compared to the calibration colour strips at 6 MV x-ray energy the film's OD response matches relatively well within 3.5%. An approximate 8% reduction in measured OD to exposure was seen for 250 kVp x-rays compared to 6 MV x-rays. The film provides an adequate measurement and visually qualitative assessment of radiation exposure for levels in the range of 0 to 200 R.

Radiotherapy treatment planning is associated with uncertainties. Examples are uncertainties in the tumour location due to organ movement or the inter/intra observer variability in target definition. Different approaches to incorporate uncertainties into IMRT optimization have been proposed. In this note, we point out a relation between two previously published methods: the coverage probability approach and the concept of optimizing the expectation value of an objective function that depends on a set of random variables. Both concepts are generally different, but turn out to be equivalent in special cases.

Different technological tools have been developed to aid in the diagnosis of pigmented skin lesions, including cameras working with conventional RGB colour systems, epiluminescence microscopy and spectrophotometric methods using visible and near infrared wavelengths. All the different procedures should provide in an objective and reproducible fashion quantitative measurements of the colour and shape features of a given skin mole.

At present, many devices have been introduced in experimental stages for clinical diagnosis, mainly used to provide to the clinicians an objective, computer-assisted second opinion. As for any diagnostic instruments, optical devices should also be subjected to a dedicated quality assurance protocol in order to evaluate the response repeatability of each device (intra-instrument agreement) and to check the accordance among the responses of different devices (inter-instrument agreement).

The aim of this study was to design a quality assurance protocol for optical devices dedicated to image analysis of pigmented skin lesions and, in case, to detect cutaneous melanoma by using suitable tissue-like phantoms as standard references that enable testing of both hardware and software components.

As an example, we report the results of intra-instrument and inter-instrument agreement when the protocol was applied on a series of 30 SpectroShade® instruments, a novel optical device based on multi-spectral image analysis of colour and shape features of pigmented skin lesion.

The Monte Carlo (MC) method provides the most accurate to-date dose calculations in heterogeneous media and complex geometries, and this spawns increasing interest in incorporating MC calculations in the treatment planning quality assurance process. This process involves MC dose calculations for the treatment plans produced clinically. Commonly used in radiotherapy, MC codes are BEAMnrc and DOSXYZnrc, which transport particles in a coordinate system (c.s.) that has been established historically and does not correspond to the c.s. of treatment planning systems (TPSs). Relative rotations of these c.s. are not straightforward, especially for non-coplanar treatments. Transformation equations are therefore required to re-calculate a treatment plan using BEAM/DOSXYZnrc codes. This paper presents such transformations for beam angles defined in a DICOM-compliant treatment planning coordinate system. Verification of the derived transformations with two three-field plans simulated on a phantom using TPS as well as MC codes has been performed demonstrating exact geometrical agreement of the MC treatment fields' placement.

A corrigendum for this article has been published in 2007 Phys. Med. Biol.52 4007.

This book provides comprehensive coverage of the subject of intensity modulated radiotherapy and the associated imaging. Most of the names associated with advanced radiotherapy can be found among the 80 authors and the book is therefore an authoritative reference text. The early chapters deal with the basic principles and include an interesting comparison between views of quality assurance for IMRT from Europe and North America. It is refreshing to see that the advice given has moved on from the concept of individual patient based quality control to more generic testing of the delivery system. However, the point is made that the whole process including the data transfer needs to be quality assured and the need for thorough commissioning of the process is emphasised. The `tricks' needed to achieve a dose based IMRT plan are well covered by the group at Ghent and there is an interesting summary of biological aspects of treatment planning for IMRT by Andrzej Niemierko.

The middle section of the book deals with advanced imaging aspects of both treatment planning and delivery. The contributions of PET and MR imaging are well covered and there is a rather rambling section on molecular imaging. Image guidance in radiotherapy treatment is addressed including the concept of adaptive radiotherapy. The treatment aspects could perhaps have merited some more coverage, but there is a very thorough discussion of 4D techniques. The final section of the book considers each site of the body in turn. This will be found useful by those wishing to embark on IMRT in a new area, although some of the sections are more comprehensive than others.

The book contains a wealth of interesting and thought provoking articles giving details as well as broad principles, and would be a useful addition to every departmental library. The editors have done a good job of ensuring that the different chapters are complementary, and of encouraging a systematic approach to the descriptions of IMRT in different anatomical sites, each of which ends with a look ahead to the future. It is something of a challenge to keep a book devoted to a rapidly developing technique up to date. Inspection of the references suggests that most of the text was completed in 2004, but the choice of world renowned authors means that the text very much represents the state of the art. The book is well presented with many colour images and justifies its £110 price tag. However, there are some signs of it having been produced within a short time scale, such as an inadequate index which cannot be relied on to lead the reader to all, or even the most relevant, discussion on a particular topic. This book should make a significant contribution to widening the use of this important advance in radiation therapy techniques.