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Physics in Medicine & Biology (PMB) awards its 'Citations Prize' to the authors of the original research paper that has received the most citations in the preceding five years (according to the Institute for Scientific Information (ISI)). The lead author of the winning paper is presented with the Rotblat Medal (named in honour of Professor Sir Joseph Rotblat who was the second—and longest serving—Editor of PMB, from 1961–1972). The winning co-authors each receive a certificate.

Some of the winning authors with their certificates, and Christian Morel with the Rotblat Medal, at the award ceremony in Orsay, near Paris. From left to right are Corinne Groiselle, Lydia Maigne, David Brasse, Irène Buvat, Dimitris Visvikis, Giovanni Santin, Uwe Pietrzyk, Pierre-François Honore, Christian Morel, Sébastien Jan and Arion Chatziioannou.

The winner of the 2009 Citations Prize for the paper which has received the most citations in the previous 5 years (2004–2008) is

GATE: a simulation toolkit for PET and SPECT Authors: S Jan, G Santin, D Strul, S Staelens, K Assié, D Autret, S Avner, R Barbier, M Bardiès, P M Bloomfield, D Brasse, V Breton, P Bruyndonckx, I Buvat, A F Chatziioannou, Y Choi, Y H Chung, C Comtat, D Donnarieix, L Ferrer, S J Glick, C J Groiselle, D Guez, P-F Honore, S Kerhoas-Cavata, A S Kirov, V Kohli, M Koole, M Krieguer, D J van der Laan, F Lamare, G Largeron, C Lartizien, D Lazaro, M C Maas, L Maigne, F Mayet, F Melot, C Merheb, E Pennacchio, J Perez, U Pietrzyk, F R Rannou, M Rey, D R Schaart, C R Schmidtlein, L~Simon, T Y Song, J-M Vieira, D Visvikis, R Van de Walle, E Wieörs and C Morel Reference: S Jan et al 2004 Phys. Med. Biol.49 4543–61

Since its publication in 2004 this article has received over 200 citations. This extremely high figure is a testament to the great influence and usefulness of the work to the nuclear medicine community. More discussion of the winning paper can be found on medicalphysicsweb.

Steve Webb Editor-in-Chief

Simon HarrisPublisher

A method is proposed to determine the cone–beam x-ray acquisition geometry of an imaging system using a phantom consisting of discrete x-ray opaque markers defining two parallel rings sharing a common axis. The phantom generates an image of two ellipses which are fitted to an ellipse model. A phantom-centric coordinate system is used to simplify the equations describing the ellipse coefficients such that a solution describing the acquisition geometry can be obtained via numerical optimization of only three of the nine unknown variables. We perform simulations to show how errors in the fit of the ellipse coefficients affect estimates of the acquisition geometries. These simulations show that for ellipse projections sampled with 1200 markers, 25 µm errors in marker positions and a source–detector distance (SDD) of 1.6 m, we can measure angles describing detector rotation with a mean error of <0.002° and a standard deviation (SD) of <0.03°. The SDD has a mean error of 0.004 mm and SD = 0.24 mm. The largest error is associated with the determination of the point on the detector closest to the x-ray source (mean error = 0.05 mm, SD = 0.85 mm). A prototype phantom was built and results from x-ray experiments are presented.

Methods of measuring uncertainties in rigid body image registration of fan beam computed tomography (FBCT) to cone beam CT (CBCT) have been developed for automatic image registration algorithms in a commercial image guidance system (Synergy, Elekta, UK). The relationships between image registration uncertainty and both imaging dose and image resolution have been investigated with an anthropomorphic skull phantom and further measurements performed with patient images of the head. A new metric of target registration error is proposed. The metric calculates the mean distance traversed by a set of equi-spaced points on the surface of a 5 cm sphere, centred at the isocentre when transformed by the residual error of registration. Studies aimed at giving practical guidance on the use of the Synergy automated image registration, including choice of algorithm and use of the Clipbox are reported. The chamfer-matching algorithm was found to be highly robust to the increased noise induced by low-dose acquisitions. This would allow the imaging dose to be reduced from the current clinical norm of 2 mGy to 0.2 mGy without a clinically significant loss of accuracy. A study of the effect of FBCT slice thickness/spacing and CBCT voxel size showed that 2.5 mm and 1 mm, respectively, gave acceptable image registration performance. Registration failures were highly infrequent if the misalignment was typical of normal clinical set-up errors and these were easily identified. The standard deviation of translational registration errors, measured with patient images, was 0.5 mm on the surface of a 5 cm sphere centred on the treatment centre. The chamfer algorithm is suitable for routine clinical use with minimal need for close inspection of image misalignment.

In this work we present a study of the impact of considering higher order terms in Molière's multiple Coulomb scattering (MCS) theory for the purpose of calculating scanning proton pencil beam lateral dose profiles in water. The proton beam profile in air, just before entering the target medium, was modeled with a sum of Gaussians fitted with measured data. The subsequent proton scattering in water was described using the three-term Molière distribution, which covers both small- and large-angle scatterings. We compared measured and computed lateral dose profiles at the 2 cm and at the near-Bragg peak depths for proton pencil beams with energies of 72.5 MeV, 121.2 MeV, 163.9 MeV and 221.8 MeV. At shallow depths, the Coulomb interaction model provided a good description of the profiles for all energies, except for 221.8 MeV. At the near-Bragg peak depths, the Coulomb interaction model provided a good description of the profiles only for the 72.5 MeV. The observed discrepancies may be attributed to the additional contributions from nuclear interactions, which may be quantified only after an accurate description of the MCS. The analysis presented in this work did not require user-adjustable parameters and may be carried out in a similar way for any other media, depths and proton energies.

In recent years, the temporal clustering analysis (TCA) method has been introduced to analyze functional MRI (fMRI) data without prior information about the activation patterns or experimental paradigms. It has been successfully applied to situations under which the timing of events of interest is not known. However, useful information regarding the spatial correlation of activation pixels with their neighbors is not taken into account in the original TCA (OTCA) method. In this study, we propose a new method called 'STCA' (spatial-TCA) which incorporates spatial information with the TCA method to improve the sensitivity in detecting the time window. The spatial information is defined as the correlation coefficient of the time activity curve between each pixel and its neighbors. The inclusion of spatial information can effectively reduce the contribution from noisy pixels and enhance the sensitivity. Both simulated data and in vivo fMRI experiments are employed to verify the method. Preliminary results show that the proposed method has increased the sensitivity significantly for in vivo fMRI data in detecting the activation response time as compared to both OTCA and modified TCA (MTCA). The OTCA/MTCA was applied to spatially smoothed data for various contrast–noise ratios and compared to STCA. The SNR improvements of both OCTA/MTCA are obvious but blurring effects are also visible. The STCA does not have this artifact.

The C57BL/6J laboratory mouse is commonly used in neurobiological research. Digital atlases of the C57BL/6J brain have been used for visualization, genetic phenotyping and morphometry, but currently lack the ability to accurately calculate deviations between individual mice. We developed a fully three-dimensional digital atlas of the C57BL/6J brain based on the histology atlas of Paxinos and Franklin (2001 The Mouse Brain in Stereotaxic Coordinates 2nd edn (San Diego, CA: Academic)). The atlas uses triangular meshes to represent the various structures. The atlas structures can be overlaid and deformed to individual mouse MR images. For this study, we selected 18 structures from the histological atlas. Average atlases can be created for any group of mice of interest by calculating the mean three-dimensional positions of corresponding individual mesh vertices. As a validation of the atlas' accuracy, we performed deformable registration of the lateral ventricles to 13 MR brain scans of mice in three age groups: 5, 8 and 9 weeks old. Lateral ventricle structures from individual mice were compared to the corresponding average structures and the original histology structures. We found that the average structures created using our method more accurately represent individual anatomy than histology-based atlases alone, with mean vertex deviations of 0.044 mm versus 0.082 mm for the left lateral ventricle and 0.045 mm versus 0.068 mm for the right lateral ventricle. Our atlas representation gives direct spatial deviations for structures of interest. Our results indicate that MR-deformable histology-based atlases represent an accurate method to obtain accurate morphometric measurements of a population of mice, and that this method may be applied to phenotyping experiments in the future as well as precision targeting of surgical procedures or radiation treatment.

The most efficient way of generating particles for Monte Carlo (MC) dose calculation is through a virtual source model (VSM) of the linear accelerator head. We have previously developed a VSM based on three sources: a primary photon source, a secondary photon source and an electron contamination source (Sikora et al 2007). In this work, we present an improvement of the electron contamination source. The VSM of contamination electrons (eVSM) is derived from a full MC simulation of the accelerator head with the BEAMnrc MC system. It comprises a Gaussian source located at the base of the flattening filter. The eVSM models two effects: an energy-dependent source diameter and an angular dependence of the particle fluence. The air scatter of the contamination electrons is approximated by energetic properties of the eVSM so that explicit in-air transport is not required during MC simulation of the dose distributions in the patient. The calculations of electron dose distributions were compared between the eVSM and the full MC simulation. Good agreement was achieved for various rectangular field sizes as well as for complex conformal segment shapes for the contamination electrons of 6 and 15 MV beams. The 3D dose evaluation of the surface dose in a CT-based patient geometry shows high accuracy (2%/2 mm) of the eVSM for both energies. The model has one tunable parameter, the mean energy of the spectrum at the patient surface. High accuracy and efficiency of particle generation make the eVSM a valuable virtual source of contamination electrons for MC treatment planning systems.

Our aim is to investigate the impact of respiratory motion on tumor quantification and delineation in static PET/CT imaging using a population of patient respiratory traces. A total of 1295 respiratory traces acquired during whole body PET/CT imaging were classified into three types according to the qualitative shape of their signal histograms. Each trace was scaled to three diaphragm motion amplitudes (6 mm, 11 mm and 16 mm) to drive a whole body PET/CT computer simulation that was validated with a physical phantom experiment. Three lung lesions and one liver lesion were simulated with diameters of 1 cm and 2 cm. PET data were reconstructed using the OS-EM algorithm with attenuation correction using CT images at the end-expiration phase and respiratory-averaged CT. The errors of the lesion maximum standardized uptake values (SUV_max) and lesion volumes between motion-free and motion-blurred PET/CT images were measured and analyzed. For respiration with 11 mm diaphragm motion and larger quiescent period fraction, respiratory motion can cause a mean lesion SUV_max underestimation of 28% and a mean lesion volume overestimation of 130% in PET/CT images with 1 cm lesions. The errors of lesion SUV_max and volume are larger for patient traces with larger motion amplitudes. Smaller lesions are more sensitive to respiratory motion than larger lesions for the same motion amplitude. Patient respiratory traces with relatively larger quiescent period fraction yield results less subject to respiratory motion than traces with long-term amplitude variability. Mismatched attenuation correction due to respiratory motion can cause SUV_max overestimation for lesions in the lower lung region close to the liver dome. Using respiratory-averaged CT for attenuation correction yields smaller mismatch errors than those using end-expiration CT. Respiratory motion can have a significant impact on static oncological PET/CT imaging where SUV and/or volume measurements are important. The impact is highly dependent upon motion amplitude, lesion location and size, attenuation map and respiratory pattern. To overcome the motion effect, motion compensation techniques may be necessary in clinical practice to improve the tumor quantification for determining the response to therapy or for radiation treatment planning.

The dosimetric performance of a Monte Carlo algorithm as implemented in a commercial treatment planning system (iPlan, BrainLAB) was investigated. After commissioning and basic beam data tests in homogenous phantoms, a variety of single regular beams and clinical field arrangements were tested in heterogeneous conditions (conformal therapy, arc therapy and intensity-modulated radiotherapy including simultaneous integrated boosts). More specifically, a cork phantom containing a concave-shaped target was designed to challenge the Monte Carlo algorithm in more complex treatment cases. All test irradiations were performed on an Elekta linac providing 6, 10 and 18 MV photon beams. Absolute and relative dose measurements were performed with ion chambers and near tissue equivalent radiochromic films which were placed within a transverse plane of the cork phantom. For simple fields, a 1D gamma (γ) procedure with a 2% dose difference and a 2 mm distance to agreement (DTA) was applied to depth dose curves, as well as to inplane and crossplane profiles. The average gamma value was 0.21 for all energies of simple test cases. For depth dose curves in asymmetric beams similar gamma results as for symmetric beams were obtained. Simple regular fields showed excellent absolute dosimetric agreement to measurement values with a dose difference of 0.1% ± 0.9% (1 standard deviation) at the dose prescription point. A more detailed analysis at tissue interfaces revealed dose discrepancies of 2.9% for an 18 MV energy 10 × 10 cm² field at the first density interface from tissue to lung equivalent material. Small fields (2 × 2 cm²) have their largest discrepancy in the re-build-up at the second interface (from lung to tissue equivalent material), with a local dose difference of about 9% and a DTA of 1.1 mm for 18 MV. Conformal field arrangements, arc therapy, as well as IMRT beams and simultaneous integrated boosts were in good agreement with absolute dose measurements in the heterogeneous phantom. For the clinical test cases, the average dose discrepancy was 0.5% ± 1.1%. Relative dose investigations of the transverse plane for clinical beam arrangements were performed with a 2D γ-evaluation procedure. For 3% dose difference and 3 mm DTA criteria, the average value for γ_>1 was 4.7% ± 3.7%, the average γ_1% value was 1.19 ± 0.16 and the mean 2D γ-value was 0.44 ± 0.07 in the heterogeneous phantom. The iPlan MC algorithm leads to accurate dosimetric results under clinical test conditions.

The incorporation of accurately aligned anatomical information as a prior to guide reconstruction and noise regularization in positron emission tomography (PET) has been suggested in many previous studies. However, the advantages of this approach can only be realized if the exact lesion outline is also available. In practice, the anatomical imaging modality may be unable to differentiate between normal and pathological tissues, and thus the edges of lesions seen in the anatomical image may not correspond to functional boundaries in the emission image. In this study, we explored an alternative approach to incorporating an anatomical prior into PET image reconstruction. Of particular interest was the realistic situation where lesions are apparent in the emission images but not in the corresponding anatomical images. In the proposed method, regional information obtained from the anatomical prior was used to estimate an anatomically adaptive anisotropic median-diffusion filtering (AAMDF) prior. This smoothing prior was determined and applied adaptively to each anatomical region on the emission image and then assembled to form a prior image for the next iteration in the reconstruction process. We formulated a two-step joint estimation reconstruction scheme to update the estimated image and prior image iteratively. The proposed AAMDF prior was evaluated and compared with maximum a posteriori (MAP) reconstruction methods with and without anatomical side information. In experiments using synthetic and physical phantom data, the AAMDF prior yielded overall higher lesion-to-background contrast and less error in lesion estimation than other algorithms for a comparable level of background noise. We conclude that lesion contrast and quantification can be improved using an anatomically derived smoothing prior without requiring knowledge of the lesion boundary. This may have important implications in clinical PET/CT, where lesion boundaries are often not obtainable from CT images.

We sought to characterize interchangeability and agreement between cone-beam computed tomography (CBCT) and digital stereoscopic kV x-ray (KVX) acquisition, two methods of isocenter positional verification currently used for IGRT of head and neck cancers (HNC). A cohort of 33 patients were near-simultaneously imaged by in-room KVX and CBCT. KVX and CBCT shifts were suggested using manufacturer software for the lateral (X), vertical (Y) and longitudinal (Z) dimensions. Intra-method repeatability, systematic and random error components were calculated for each imaging modality, as were recipe-based PTV expansion margins. Inter-method agreement in each axis was compared using limits of agreement (LOA) methodology, concordance analysis and orthogonal regression. 100 daily positional assessments were performed before daily therapy in 33 patients with head and neck cancer. Systematic error was greater for CBCT in all axes, with larger random error components in the Y- and Z-axis. Repeatability ranged from 9 to 14 mm for all axes, with CBCT showing greater repeatability in 2/3 axes. LOA showed paired shifts to agree 95% of the time within ±11.3 mm in the X-axis, ±9.4 mm in the Y-axis and ±5.5 mm in the Z-axis. Concordance ranged from 'mediocre' to 'satisfactory'. Proportional bias was noted between paired X- and Z-axis measures, with a constant bias component in the Z-axis. Our data suggest non-negligible differences in software-derived CBCT and KVX image-guided directional shifts using formal method comparison statistics.

A correction was made to the first line of page 7404 of this article on 26 November 2009. The corrected electronic version is identical to the print version.

A comprehensive system characterisation was performed of the Eckert & Ziegler BEBIG GmbH MultiSource® High Dose Rate (HDR) brachytherapy treatment unit with an ¹⁹²Ir source. The unit is relatively new to the UK market, with the first installation in the country having been made in the summer of 2009. A detailed commissioning programme was devised and is reported including checks of the fundamental parameters of source positioning, dwell timing, transit doses and absolute dosimetry of the source. Well chamber measurements, autoradiography and video camera analysis techniques were all employed. The absolute dosimetry was verified by the National Physical Laboratory, UK, and compared to a measurement based on a calibration from PTB, Germany, and the supplied source certificate, as well as an independent assessment by a visiting UK centre. The use of the 'Krieger' dosimetry phantom has also been evaluated. Users of the BEBIG HDR system should take care to avoid any significant bend in the transfer tube, as this will lead to positioning errors of the source, of up to 1.0 mm for slight bends, 2.0 mm for moderate bends and 5.0 mm for extreme curvature (depending on applicators and transfer tube used) for the situations reported in this study. The reason for these errors and the potential clinical impact are discussed. Users should also note the methodology employed by the system for correction of transit doses, and that no correction is made for the initial and final transit doses. The results of this investigation found that the uncorrected transit doses lead to small errors in the delivered dose at the first dwell position, of up to 2.5 cGy at 2 cm (5.6 cGy at 1 cm) from a 10 Ci source, but the transit dose correction for other dwells was accurate within 0.2 cGy. The unit has been mechanically reliable, and source positioning accuracy and dwell timing have been reproducible, with overall performance similar to other existing HDR equipment. The unit is capable of high quality brachytherapy treatment delivery, taking the above factors into account.

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