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Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs > 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Proton imaging is a promising technology for proton radiotherapy as it can be used for: (1) direct sampling of the tissue stopping power, (2) input information for multi-modality RSP reconstruction, (3) gold-standard calibration against concurrent techniques, (4) tracking motion and (5) pre-treatment positioning. However, no end-to-end characterization of the image quality (signal-to-noise ratio and spatial resolution, blurring uncertainty) against the dose has been done. This work aims to establish a model relating these characteristics and to describe their relationship with proton energy and object size. The imaging noise originates from two processes: the Coulomb scattering with the nucleus, producing a path deviation, and the energy loss straggling with electrons. The noise is found to increases with thickness crossed and, independently, decreases with decreasing energy. The scattering noise is dominant around high-gradient edge whereas the straggling noise is maximal in homogeneous regions. Image quality metrics are found to behave oppositely against energy: lower energy minimizes both the noise and the spatial resolution, with the optimal energy choice depending on the application and location in the imaged object. In conclusion, the model presented will help define an optimal usage of proton imaging to reach the promised application of this technology and establish a fair comparison with other imaging techniques.

A maximum likelihood approach to the problem of calculating the proton paths inside the scanned object in proton computed tomography is presented. Moliere theory is used for first time to derive a physical model that describes proton multiple Coulomb scattering, avoiding the need for the Gaussian approximation currently used. To enable this, the proposed method approximates proton paths with cubic Bezier curves and subsequently maximizes the path likelihood through parametric optimization, based on the Moliere model. Results from the Highland formula-based Gaussian approximation are also presented for comparison. The simplex method is utilized for optimisation. The scattering properties of the material(s) of the scanned object are taken into account by appropriately calculating the scattering parameters from the stopping power map that is calculated/updated at every iteration of the algebraic reconstruction process. Proton track length constraint imposed by the proton energy loss is also accounted for. The method is also applied in the case that no exit angle data are measured. Geant4 Monte Carlo simulations were performed for model validation. Our results show that use of Moliere probability density function for modelling the multiple Coulomb scattering presents a modest 2% accuracy improvement over the Gaussian approximation and most-likely-path method. Simulations of voxelized phantom showed no essential benefit from the inclusion of the material information into the optimization, while path optimization with energy constraint slightly increased path resolution in a bone/water interface phantom. Method error was found to depend on energy, proton track-length within the medium, and proportion of data filtering.

ObjectivesThe Dietetic Assessment and Intervention in Lung Cancer (DAIL) study was an observational cohort study. It triaged the need for dietetic input in patients with lung cancer, using questionnaires with 137 responses. This substudy tested if machine learning could predict need to see a dietitian (NTSD) using 5 or 10 measures.Methods76 cases from DAIL were included (Royal Surrey NHS Foundation Trust; RSH: 56, Frimley Park Hospital; FPH 20). Univariate analysis was used to find the strongest correlates with NTSD and ‘critical need to see a dietitian’ CNTSD. Those with a Spearman correlation above ±0.4 were selected to train a support vector machine (SVM) to predict NTSD and CNTSD. The 10 and 5 best correlates were evaluated.Results18 and 13 measures had a correlation above ±0.4 for NTSD and CNTSD, respectively, producing SVMs with 3% and 7% misclassification error. 10 measures yielded errors of 7% (NTSD) and 9% (CNTSD). 5 measures yielded between 7% and 11% errors. SVM trained on the RSH data and tested on the FPH data resulted in errors of 20%.ConclusionsMachine learning can predict NTSD producing misclassification errors

Highlights • A novel proton CT imaging system, based entirely on solid-state detector technology. • First proton CT scan with solid-state detectors. • Potential for short scan times as well as improvement in RSP accuracy., Purpose Proton CT is widely recognised as a beneficial alternative to conventional X-ray CT for treatment planning in proton beam radiotherapy. A novel proton CT imaging system, based entirely on solid-state detector technology, is presented. Compared to conventional scintillator-based calorimeters, positional sensitive detectors allow for multiple protons to be tracked per read out cycle, leading to a potential reduction in proton CT scan time. Design and characterisation of its components are discussed. An early proton CT image obtained with a fully solid-state imaging system is shown and accuracy (as defined in Section IV) in Relative Stopping Power to water (RSP) quantified. Method A solid-state imaging system for proton CT, based on silicon strip detectors, has been developed by the PRaVDA collaboration. The system comprises a tracking system that infers individual proton trajectories through an imaging phantom, and a Range Telescope (RT) which records the corresponding residual energy (range) for each proton. A back-projection-then-filtering algorithm is used for CT reconstruction of an experimentally acquired proton CT scan. Results An initial experimental result for proton CT imaging with a fully solid-state system is shown for an imaging phantom, namely a 75 mm diameter PMMA sphere containing tissue substitute inserts, imaged with a passively-scattered 125 MeV beam. Accuracy in RSP is measured to be ⩽1.6% for all the inserts shown. Conclusions A fully solid-state imaging system for proton CT has been shown capable of imaging a phantom with protons and successfully improving RSP accuracy. These promising results, together with system the capability to cope with high proton fluences (2×108 protons/s), suggests that this research platform could improve current standards in treatment planning for proton beam radiotherapy.

Medical physics has been central to the scientific and technical development of radiotherapy since its inception as a treatment modality for cancer patients. Radiotherapy centres, as well as delivering a safe and effective cancer treatment, are routinely implementing innovations into the clinic (Jacobs et al 2016) and physicists are central to innovation generation and innovation adoption. Bortfeld and Jeraj (2011) highlighted the historic achievements of physics research in radiation therapy (radiotherapy) and argued for the continuing role, and need to develop academic medical physics and radiotherapy physics research. Following up on this, Bortfeld et al (2015) identified the potential risk of the radiotherapy physics profession having only a clinical physicist role and argued strongly for the need for academic positions. This was supported more recently by Klein et al (2017) who highlighted the need for physicists who can adapt to changes caused by the rapid evolution and expansion of radiotherapy technology and imaging options within the clinic. The recent review of global radiation therapy research by Aggarwal et al (2018) highlighted physics research as an important metric and area of research within radiation therapy.

Aims To evaluate the feasibility and heart-sparing ability of the voluntary breath-hold (VBH) technique in a multicentre setting. Materials and methods Patients were recruited from 10 UK centres. Following surgery for early left breast cancer, patients with any heart inside the 50% isodose from a standard free-breathing tangential field treatment plan underwent a second planning computed tomography (CT) scan using the VBH technique. A separate treatment plan was prepared on the VBH CT scan and used for treatment. The mean heart, left anterior descending coronary artery (LAD) and lung doses were calculated. Daily electronic portal imaging (EPI) was carried out and scanning/treatment times were recorded. The primary end point was the percentage of patients achieving a reduction in mean heart dose with VBH. Population systematic (Σ) and random errors (σ) were estimated. Within-patient comparisons between techniques used Wilcoxon signed-rank tests. Results In total, 101 patients were recruited during 2014. Primary end point data were available for 93 patients, 88 (95%) of whom achieved a reduction in mean heart dose with VBH. Mean cardiac doses (Gy) for free-breathing and VBH techniques, respectively, were: heart 1.8 and 1.1, LAD 12.1 and 5.4, maximum LAD 35.4 and 24.1 (all P

This study enables a comparison between two proposed algorithms in the literature for proton computed tomography (pCT) reconstruction; these are the analytical filtered back-projection (FBP) and the iterative algorithm of diagonally relaxed orthogonal projections (DROP) with total variation superiorization (TVS). The analytical model of the cubic spline path (CSP) has been implemented into DROP-TVS algorithm to account for scattering, using measurements of individual proton positions/trajectories and energy before and after traversing a selected phantom. Spatial resolution and relative stopping power (RSP) accuracy of the reconstructed images were used as comparison criteria. Parametric changes of projection angular ranges from 00 to 1800 and 00 to 3600, as well as angular steps of 0.50 and 10 have been investigated. Experimental data of the CT0404 "Sensitom" and the CTP528 "Line Pair" modules of the Catphan® 600 phantom were used. DROP-TVS appeared to provide better noise reduction compared to FBP while the resolution worsened with reduced projections. On the other hand, FBP resulted in degraded image quality with more noise and worse spatial resolution compared to that of the DROP-TVS scheme. Interplane artifacts were present with both algorithms which became more acute in FBP reconstructions and with a limited number of projections. Reduced number of projections had an adverse effect on both reconstruction methods. The study outcomes highlight the optimal acquisition for pCT reconstruction for superior image quality but there must always be a trade-off between noise and spatial resolution for optimal data acquisition.

Proton computed tomography (pCT) offers unique image formation attributes, with a potential for increasing accuracy of treatment planning in proton beam therapy. To maximize the potential of pCT it is necessary to develop advanced reconstruction algorithms that can accurately recover relative proton stopping power maps. This study aims to integrate pCT into STIR (Software for Tomographic Image Reconstruction), a popular Multi-Platform Object-Oriented framework for reconstruction in tomographic imaging to benefit from its software infrastructure. Open source STIR library is currently suitable for reconstructing and manipulating data from Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), which are based on cylindrical scanner geometries. Although pCT has a noncylindrical geometry, STIR provides the framework for single event detection and modelling of the proton interactions. This initial implementation includes classes and functions with new features such as general proton scanner geometry, binning of list mode proton data into sinograms and uses analytical reconstruction algorithms already available in STIR. The structure of the new implemented features is discussed. Future work will include additional components to establish STIR as a potential toolkit for pCT image reconstruction.

This paper studies the sensitivity of a range of image texture parameters used in radiomics to: (i) the number of intensity levels, (ii) the method of quantisation to select the intensity levels and (iii) the use of an intensity threshold. 43 commonly used texture features were studied for the gross target volume outlined on the CT component of PET/CT scans of 50 patients with non-small cell lung carcinoma (NSCLC). All cases were quantised for all values between 4 and 128 intensity levels using four commonly used quantisation methods. All results were analysed with and without a threshold range of -200 HU to 300 HU. Cases were ranked for each texture feature and for all quantisation methods with the Spearman's rank correlation coefficient determined to evaluate stability. Results showed large fluctuations in ranking, particularly for low numbers of levels, differences between quantisation methods and with the use of a threshold, with values Spearman's Rank Correlation for many parameters below 0.2. Our results demonstrated the sensitivity of radiomics features to the parameters used during analysis and highlight the risk of low reproducibility comparing studies with slightly different parameters. In terms of the lung cancer CT datasets, this study supports the use of 128 intensity levels, the same uniform quantiser applied to all scans and thresholding of the data. It also supports several of the features recommended in the literature for such studies such as skewness and kurtosis. A recommended framework is presented for curation of the data analysis process to ensure stability of results.

A Machine Learning approach to the problem of calculating the proton paths inside a scanned object in proton Computed Tomography is presented. The method is developed in order to mitigate the loss in both spatial resolution and quantitative integrity of the reconstructed images caused by multiple Coulomb scattering of protons traversing the matter. Two Machine Learning models were used: a forward neural network (NN) and the XGBoost method. A heuristic approach, based on track averaging was also implemented in order to evaluate the accuracy limits on track calculation, imposed by the statistical nature of the scattering. Synthetic data from anthropomorphic voxelized phantoms, generated by the Monte Carlo (MC) Geant4 code, were utilized to train the models and evaluate their accuracy, in comparison to a widely used analytical method that is based on likelihood maximization and Fermi−Eyges scattering model. Both NN and XGBoost model were found to perform very close or at the accuracy limit, further improving the accuracy of the analytical method (by 12% in the typical case of 200 MeV protons on 20 cm of water object), especially for protons scattered at large angles. Inclusion of the material information along the path in terms of radiation length did not show improvement in accuracy for the phantoms simulated in the study. A NN was also constructed to predict the error in path calculation, thus enabling a criterion to filter out proton events that may have a negative effect on the quality of the reconstructed image. By parametrizing a large set of synthetic data, the Machine Learning models were proved capable to bring—in an indirect and time efficient way—the accuracy of the MC method into the problem of proton tracking.

Background and purpose: To evaluate non-coplanar volumetric modulated arc radiotherapy (VMAT) trajectories for organ at risk (OAR) sparing in primary brain tumour radiotherapy. Materials and methods: Fifteen patients were planned using coplanar VMAT and compared against non-coplanar VMAT plans for three trajectory optimization techniques. A geometric heuristic technique (GH) combined beam scoring and Dijkstra's algorithm to minimize the importance-weighted sum of OAR volumes irradiated. Fluence optimization was used to perform a local search around coplanar and GH trajectories, producing fluence-based local search (FBLS) and FBLS+GH trajectories respectively. Results: GH, FBLS, and FBLS+GH trajectories reduced doses to the contralateral globe, optic nerve, hippocampus, temporal lobe, and cochlea. However, FBLS increased dose to the ipsilateral lens, optic nerve and globe. Compared to GH, FBLS+GH increased dose to the ipsilateral temporal lobe and hippocampus, contralateral optics, and the brainstem and body. GH and FBLS+GH trajectories reduced bilateral hippocampi normal tissue complication probability (p = 0.028 and p = 0.043, respectively). All techniques reduced PTV conformity; GH and FBLS+GH trajectories reduced homogeneity but less so for FBLS+GH. Conclusions: The geometric heuristic technique best spared OARs and reduced normal tissue complication probability, however incorporating fluence information into non-coplanar trajectory optimization maintained PTV homogeneity.

Several studies have recently reported on the value of CT texture analysis in predicting survival, although the topic remains controversial, with further validation needed in order to consolidate the evidence base. The aim of this study was to investigate the effect of varying the input parameters in the Kaplan–Meier analysis, to determine whether the resulting P-value can be considered to be a robust indicator of the parameter's prognostic potential. A retrospective analysis of the CT-based normalised entropy of 51 patients with lung cancer was performed and overall survival data for these patients were collected. A normalised entropy cut-off was chosen to split the patient cohort into two groups and log-rank testing was performed to assess the survival difference of the two groups. This was repeated for varying normalised entropy cut-offs and varying follow-up periods. Our findings were also compared with previously published results to assess robustness of this parameter in a multi-centre patient cohort. The P-value was found to be highly sensitive to the choice of cut-off value, with small changes in cut-off producing substantial changes in P. The P-value was also sensitive to follow-up period, with particularly noisy results at short follow-up periods. Using matched conditions to previously published results, a P-value of 0.162 was obtained. Survival analysis results can be highly sensitive to the choice in texture cut-off value in dichotomising patients, which should be taken into account when performing such studies to avoid reporting false positive results. Short follow-up periods also produce unstable results and should therefore be avoided to ensure the results produced are reproducible. Previously published findings that indicated the prognostic value of normalised entropy were not replicated here, but further studies with larger patient numbers would be required to determine the cause of the different outcomes.

To determine the effect of image-guided radiotherapy on the dose distributions in breast boost treatments.Computed tomography images from a cohort of 60 patients treated within the IMPORT HIGH trial (CRUK/06/003) were used to create sequential and concomitant boost treatment plans (30 cases each). Two treatment plans were created for each case using tumour bed planning target volume (PTV) margins of 5 mm (achieved with image-guided radiotherapy) and 8 mm (required for bony anatomy verification). Dose data were collected for breast, lung and heart; differences with margin size were tested for statistical significance.A median decrease of 29 cm(3) (range 11-193 cm(3)) of breast tissue receiving 95% of the prescribed dose was observed where image-guided radiotherapy margins were used. Decreases in doses to lungs, contralateral breast and heart were modest, but statistically significant (P 0.01). Plan quality was compromised with the 8 mm PTV margin in one in eight sequential boost plans and one third of concomitant boost plans. Tumour bed PTV coverage was95% (91%) of the prescribed dose in 12 cases; in addition, the required partial breast median dose was exceeded in nine concomitant boost cases by 0.5-3.7 Gy.The use of image guidance and, hence, a reduced tumour bed PTV margin, in breast boost radiotherapy resulted in a modest reduction in radiation dose to breast, lung and heart tissues. Reduced margins enabled by image guidance were necessary to discriminate between dose levels to multiple PTVs in the concomitant breast boost plans investigated.

Recently CMOS Active Pixels Sensors (APSs) have become a valuable alternative to amorphous Silicon and Selenium Flat Panel Imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ≤ 1.9%. The uniformity of the image quality performance has been further investigated in a typical X-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practise. Finally, in order to compare the detection capability of this novel APS with the currently used technology (i.e. FPIs), theoretical evaluation of the Detection Quantum Efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this detector compared to FPIs. Optical characterization, X-ray contrast measurements and theoretical DQE evaluation suggest that a trade off can be found between the need of a large imaging area and the requirement of a uniform imaging performance, making the DynAMITe large area CMOS APS suitable for a range of bio-medical applications.

This study investigates the use of a mechanically-swept 3D ultrasound (3D-US) probe for soft-tissue displacement monitoring during prostate irradiation, with emphasis on quantifying the accuracy relative to CyberKnife® x-ray fiducial tracking. An US phantom, implanted with x-ray fiducial markers was placed on a motion platform and translated in 3D using five real prostate motion traces acquired using the Calypso system. Motion traces were representative of all types of motion as classified by studying Calypso data for 22 patients. The phantom was imaged using a 3D swept linear-array probe (to mimic trans-perineal imaging) and, subsequently, the kV x-ray imaging system on CyberKnife. A 3D cross-correlation block-matching algorithm was used to track speckle in the ultrasound data. Fiducial and US data were each compared with known phantom displacement. Trans-perineal 3D-US imaging could track superior–inferior (SI) and anterior–posterior (AP) motion to ≤0.81 mm root-mean-square error (RMSE) at a 1.7 Hz volume rate. The maximum kV x-ray tracking RMSE was 0.74 mm, however the prostate motion was sampled at a significantly lower imaging rate (mean: 0.04 Hz). Initial elevational (right–left; RL) US displacement estimates showed reduced accuracy but could be improved (RMSE

Objective: This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests, FEV1 (forced expiratory volume in 1 s) and TLCO (transfer factor of carbon monoxide). Methods: An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it. Results: Density and entropy scores were compared between a cohort of 29 fit patients (defined as FEV1 and TLCO above 50 % predicted value) and 32 unfit patients (FEV1 or TLCO below 50% predicted). Mean and median density and median entropy were significantly different between fit and unfit patients (p = 0.005, 0.0008 and 0.0418 respectively; two-sided Mann–Whitney test). Conclusion: Density and entropy assessment can differentiate between fit and unfit patients for radical radiotherapy, using standard CT imaging. Advances in knowledge: This study shows that a novel assessment can generate further data from standard CT imaging. These data could be combined with existing studies to form a multiorgan patient fitness assessment from a single CT scan.

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra's algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V-50 (Gy) and V-60 (Gy) were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

Purpose To determine whether voluntary deep-inspiratory breath-hold (v-DIBH) and deep-inspiratory breath-hold with the active breathing coordinator™ (ABC-DIBH) in patients undergoing left breast radiotherapy are comparable in terms of normal-tissue sparing, positional reproducibility and feasibility of delivery. Methods Following surgery for early breast cancer, patients underwent planning-CT scans in v-DIBH and ABC-DIBH. Patients were randomised to receive one technique for fractions 1-7 and the second technique for fractions 8-15 (40 Gy/15 fractions total). Daily electronic portal imaging (EPI) was performed and matched to digitally-reconstructed radiographs. Cone-beam CT (CBCT) images were acquired for 6/15 fractions and matched to planning-CT data. Population systematic (Σ) and random errors (σ) were estimated. Heart, left-anterior-descending coronary artery, and lung doses were calculated. Patient comfort, radiographer satisfaction and scanning/treatment times were recorded. Within-patient comparisons between the two techniques used the paired t-test or Wilcoxon signed-rank test. Results Twenty-three patients were recruited. All completed treatment with both techniques. EPI-derived Σ were ≤1.8 mm (v-DIBH) and ≤2.0 mm (ABC-DIBH) and σ ≤2.5 mm (v-DIBH) and ≤2.2 mm (ABC-DIBH) (all p non-significant). CBCT-derived Σ were ≤3.9 mm (v-DIBH) and ≤4.9 mm (ABC-DIBH) and σ ≤ 4.1 mm (v-DIBH) and ≤ 3.8 mm (ABC-DIBH). There was no significant difference between techniques in terms of normal-tissue doses (all p non-significant). Patients and radiographers preferred v-DIBH (p = 0.007, p = 0.03, respectively). Scanning/treatment setup times were shorter for v-DIBH (p = 0.02, p = 0.04, respectively). Conclusions v-DIBH and ABC-DIBH are comparable in terms of positional reproducibility and normal tissue sparing. v-DIBH is preferred by patients and radiographers, takes less time to deliver, and is cheaper than ABC-DIBH. © 2013 Elsevier Ireland Ltd. All rights reserved.

This work investigates the feasibility of using a prototype complementary metal oxide semiconductor active pixel sensor (CMOS APS) for real-time verification of volumetric modulated arc therapy (VMAT) treatment. The prototype CMOS APS used region of interest read out on the chip to allow fast imaging of up to 403.6 frames per second (f/s). The sensor was made larger (5.4 cm × 5.4 cm) using recent advances in photolithographic technique but retains fast imaging speed with the sensor's regional read out. There is a paradigm shift in radiotherapy treatment verification with the advent of advanced treatment techniques such as VMAT. This work has demonstrated that the APS can track multi leaf collimator (MLC) leaves moving at 18 mm s(-1) with an automatic edge tracking algorithm at accuracy better than 1.0 mm even at the fastest imaging speed. Evaluation of the measured fluence distribution for an example VMAT delivery sampled at 50.4 f/s was shown to agree well with the planned fluence distribution, with an average gamma pass rate of 96% at 3%/3 mm. The MLC leaves motion and linac pulse rate variation delivered throughout the VMAT treatment can also be measured. The results demonstrate the potential of CMOS APS technology as a real-time radiotherapy dosimeter for delivery of complex treatments such as VMAT.

The AccuLeaf mMLC featuring four multileaf-collimator (MLC) banks has been used for the first time for an experimental comparison of conventional two-bank with novel four-bank dynamic MLC tracking of a two-dimensional sinusoidal respiratory motion. This comparison was performed for a square aperture, and for three conformal treatment apertures from clinical radiotherapy lung cancer patients. The system latency of this prototype tracking system was evaluated and found to be 1.0 s and the frequency at which MLC positions could be updated, 1 Hz, and therefore accurate MLC tracking of irregular patient motion would be difficult with the system in its current form. The MLC leaf velocity required for two-bank-MLC and four-bank-MLC tracking was evaluated for the apertures studied and a substantial decrease was found in the maximum MLC velocity required when four-banks were used for tracking rather than two. A dosimetric comparison of the two techniques was also performed and minimal difference was found between two-bank-MLC and four-bank-MLC tracking. The use of four MLC banks for dynamic MLC tracking is shown to be potentially advantageous for increasing the delivery efficiency compared with two-bank-MLC tracking where difficulties are encountered if large leaf shifts are required to track motion perpendicular to the direction of leaf travel.

Objective: The purpose of the work was to estimate the dose received by the heart throughout a course of breath-holding breast radiotherapy. Methods: 113 cone-beam CT (CBCT) scans were acquired for 20 patients treated within the HeartSpare 1A study, in which both an active breathing control (ABC) device and a voluntary breath-hold (VBH) method were used. Predicted mean heart doses were obtained from treatment plans. CBCT scans were imported into a treatment planning system, heart outlines defined, images registered to the CT planning scan and mean heart dose recorded. Two observers outlined two cases three times each to assess interobserver and intraobserver variation. Results: There were no statistically significant differences between ABC and VBH heart dose data from CT planning scans, or in the CBCT-based estimates of heart dose, and no effect from the order of the breath-hold method. Variation in mean heart dose per fraction over the three imaged fractions was

Purpose: To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer. Method: Doses from breast radiotherapy and kilovoltage cone beam CT(CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB. Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organdoses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCTimaging. Results: All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (

Purpose This study investigates (i) the effect of verification protocols on treatment accuracy and PTV margins for partial breast and boost breast radiotherapy with short fractionation schema (15 fractions), (ii) the effect of deformation of the excision cavity (EC) on PTV margin size, (iii) the imaging dose required to achieve specific PTV margins. Methods and materials Verification images using implanted EC markers were studied in 36 patients. Target motion was estimated for a 15 fraction partial breast regimen using imaging protocols based on on-line and off-line motion correction strategies (No Action Level (NAL) and the extended NAL (eNAL) protocols). Target motion was used to estimate a PTV margin for each protocol. To evaluate treatment errors due to deformation of the excision cavity, individual marker positions were obtained from 11 patients. The mean clip displacement and daily variation in clip position during radiotherapy were determined and the contribution of these errors to PTV margin calculated. Published imaging dose data were used to estimate total dose for each protocol. Finally the number of images required to obtain a specific PTV margin was evaluated and hence, the relationship between PTV margins and imaging dose was investigated. Results The PTV margin required to account for excision cavity motion, varied between 10.2 and 2.4mm depending on the correction strategy used. Average clip movement was 0.8mm and average variation in clip position during treatment was 0.4mm. The contribution to PTV margin from deformation was estimated to be small, less than 0.2mm for both off-line and on-line correction protocols. Conclusion A boost or partial breast PTV margin of ∼10mm, is possible with zero imaging dose and workload, however, patients receiving boost radiotherapy may benefit from a margin reduction of ∼4mm with imaging doses from 0.4cGy to 25cGy using an eNAL protocol. PTV margin contributions from deformation errors are likely to be small in comparison to other sources of error, i.e., set up or delineation.

Artifacts in treatment-room cone-beam reconstructions have been observed at the authors' center when cone-beam acquisition is simultaneous with radio frequency (RF) transponder tracking using the Calypso 4D system (Calypso Medical, Seattle, WA). These artifacts manifest as CT-number modulations and increased CT-noise. The authors present a method for the suppression of the artifacts.

Purpose: In this paper, the effect on image quality of significantly reducing the primary electron energy of a radiotherapy accelerator is investigated using a novel waveguide test piece. The waveguide contains a novel variable coupling device (rotovane), allowing for a wide continuously variable energy range of between 1.4 and 9 MeV suitable for both imaging and therapy.Method: Imaging at linac accelerating potentials close to 1 MV was investigated experimentally and via Monte Carlo simulations. An imaging beam line was designed, and planar and cone beam computed tomography images were obtained to enable qualitative and quantitative comparisons with kilovoltage and megavoltage imaging systems. The imaging beam had an electron energy of 1.4 MeV, which was incident on a water cooled electron window consisting of stainless steel, a 5 mm carbon electron absorber and 2.5 mm aluminium filtration. Images were acquired with an amorphous silicon detector sensitive to diagnostic x-ray energies. Results: The x-ray beam had an average energy of 220 keV and half value layer of 5.9 mm of copper. Cone beam CT images with the same contrast to noise ratio as a gantry mounted kilovoltage imaging system were obtained with doses as low as 2 cGy. This dose is equivalentmore » to a single 6 MV portal image. While 12 times higher than a 100 kVp CBCT system (Elekta XVI), this dose is 140 times lower than a 6 MV cone beam imaging system and 6 times lower than previously published LowZ imaging beams operating at higher (4-5 MeV) energies. Conclusions: The novel coupling device provides for a wide range of electron energies that are suitable for kilovoltage quality imaging and therapy. The imaging system provides high contrast images from the therapy portal at low dose, approaching that of gantry mounted kilovoltage x-ray systems. Additionally, the system provides low dose imaging directly from the therapy portal, potentially allowing for target tracking during radiotherapy treatment. There is the scope with such a tuneable system for further energy reduction and subsequent improvement in image quality.« less

Purpose: The purpose of this work was to investigate the use of an experimental complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) for tracking of moving fiducial markers during radiotherapy. Methods: The APS has an active area of 5.4 5.4 cm and maximum full frame read-out rate of 20 frame s -1, with the option to read out a region-of-interest (ROI) at an increased rate. It was coupled to a 4 mm thick ZnWO4 scintillator which provided a quantum efficiency (QE) of 8 for a 6 MV x-ray treatment beam. The APS was compared with a standard iViewGT flat panel amorphous Silicon (a-Si) electronic portal imaging device (EPID), with a QE of 0.34 and a frame-rate of 2.5 frame s -1. To investigate the ability of the two systems to image markers, four gold cylinders of length 8 mm and diameter 0.8, 1.2, 1.6, and 2 mm were placed on a motion-platform. Images of the stationary markers were acquired using the APS at a frame-rate of 20 frame s -1, and a dose-rate of 143 MU min -1 to avoid saturation. EPID images were acquired at the maximum frame-rate of 2.5 frame s -1, and a reduced dose-rate of 19 MU min -1 to provide a similar dose per frame to the APS. Signal-to-noise ratio (SNR) of the background signal and contrast-to-noise ratio (CNR) of the marker signal relative to the background were evaluated for both imagers at doses of 0.125 to 2 MU. Results: Image quality and marker visibility was found to be greater in the APS with SNR �5 times greater than in the EPID and CNR up to an order of magnitude greater for all four markers. To investigate the ability to image and track moving markers the motion-platform was moved to simulate a breathing cycle with period 6 s, amplitude 20 mm and maximum speed 13.2 mm s -1. At the minimum integration time of 50 ms a tracking algorithm applied to the APS data found all four markers with a success rate of 92 and positional error 90 m. At an integration time of 400 ms the smallest marker became difficult to detect when moving. The detection of moving markers using the a-Si EPID was difficult even at the maximum dose-rate of 592 MU min -1 due to the lower QE and longer integration time of 400 ms. Conclusions: This work demonstrates that a fast read-out, high QE APS may be useful in the tracking of moving fiducial markers during radiotherapy. Further study is required to investigate the tracking of markers moving in 3D in a treatment beam attenuated by moving patient anatomy. This will require a larger sensor with ROI read-out to maintain speed and a manageable data-rate. © 2011 American Association of Physicists in Medicine.

Three-dimensional (3D) soft tissue tracking using 3D ultrasound is of interest for monitoring organ motion during therapy. Previously we demonstrated feature tracking of respiration-induced liver motion in vivo using a 3D swept-volume ultrasound probe. The aim of this study was to investigate how object speed affects the accuracy of tracking ultrasonic speckle in the absence of any structural information, which mimics the situation in homogenous tissue for motion in the azimuthal and elevational directions. For object motion prograde and retrograde to the sweep direction of the transducer, the spatial sampling frequency increases or decreases with object speed, respectively. We examined the effect object motion direction of the transducer on tracking accuracy. We imaged a homogenous ultrasound speckle phantom whilst moving the probe with linear motion at a speed of 0-35 mm s⁻¹. Tracking accuracy and precision were investigated as a function of speed, depth and direction of motion for fixed displacements of 2 and 4 mm. For the azimuthal direction, accuracy was better than 0.1 and 0.15 mm for displacements of 2 and 4 mm, respectively. For a 2 mm displacement in the elevational direction, accuracy was better than 0.5 mm for most speeds. For 4 mm elevational displacement with retrograde motion, accuracy and precision reduced with speed and tracking failure was observed at speeds of greater than 14 mm s⁻¹. Tracking failure was attributed to speckle de-correlation as a result of decreasing spatial sampling frequency with increasing speed of retrograde motion. For prograde motion, tracking failure was not observed. For inter-volume displacements greater than 2 mm, only prograde motion should be tracked which will decrease temporal resolution by a factor of 2. Tracking errors of the order of 0.5 mm for prograde motion in the elevational direction indicates that using the swept probe technology speckle tracking accuracy is currently too poor to track homogenous tissue over a series of volume images as these errors will accumulate. Improvements could be made through increased spatial sampling in the elevational direction.

Stitched, large area, complementary metal-oxide-semiconductor (CMOS), active pixel sensors (APS) show promises for X-ray imaging applications. In this paper we present an investigation of the effects of stitching on uniformity of sensor response for an experimental APS. The sensor, known as LAS (large area sensor), was made by reticular stitching onto a single silicon wafer of a 5×5 array of regions consisting of 270×270 pixels with 40 μm pixel pitch, to yield 1350×1350 pixels and an imaging area of 54×54 mm. Data acquired from two different sensors of the same type were filtered to remove spiking pixels and electromagnetic interference (EMI). The non-linear compensation (NLC) technique for CMOS sensor analysis was used to determine the variation in gain, read noise, full well capacity and dynamic range between stitched regions. Variations across stitched regions were analysed using profiles, analysis of pixel variations at stitch boundaries and using a measurement of non-uniformity within a stitched region. The results showed that non-uniformity variations were present, which increased with signal (1.5–3.5% at dark signal, rising to 3–8%). However, these were found to be smaller than variations caused by differences in readout electronics, particularly at low signal levels. The results suggest these variations should be correctable using standard calibration methods.

The characteristics of an Elekta Precise treatment machine with a gating interface were investigated. Three detectors were used: a Farmer ionization chamber, a MatriXX ionization chamber array and an in-house, single pulse-measurement ionization chamber (IVC). Measurements were made of dosimetric accuracy, flatness and symmetry characteristics and duty cycle for a range of beam-on times and gating periods. Results were compared with a standard ungated delivery as a reference. For all beam-on times, down to 0.5 s, dosimetric differences were below +/-1% and flatness and symmetry parameter variations were below +/-1.5%. For the shorter beam-on times the in-house detector deviated from the other two detectors, suggesting that this device should be used in conjunction with other detectors for absolute dosimetry purposes. However, it was found to be useful for studying gated beam characteristics pulse by pulse.

Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed “radiomics” and includes semantic and agnostic approaches. Textural analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue subtypes of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarize the current published data and understand the potential future role of TA in managing lung cancer.

Methods: Data were acquired using a human torso phantom comprised of a hot F-18-filled spheroidal "tumor" (40 mm in diameter) suspended in an air-filled "lung" cylinder and surrounded by a warm F-18-filled background. Two different sphere-to-background (S/B) ratios were used. The tumor was connected to a 3-axis computer-controlled motion stage and could be moved during PET data acquisition. Images were acquired with a range of count statistics, motion blurring, and CT attenuation correction (CTAC) misalignment. Four simple models were proposed for the assignment of clonogenic cell density according to the voxel value. The impact of image artifacts was then assessed by calculating the TCP, which is the probability that no clonogenic tumor cell remains after a given dose of radiation. TCP was calculated for a uniform dose distribution in the tumor. Results: Reduced count statistics and misaligned CTAC images had the most detrimental impact on the image fidelity. It was found that in both cases the images became less intense, demonstrated by smaller number of voxels at the maximum values. The maximum TCP difference between images with the least and most noise was 3.4% (S/B=3), and with weakest and strongest CT misalignment artifacts, it was 3.2% (S/B=10). Motion blurring only contributed weakly to the TCP imprecision at 1.7% (S/B=10) between best- and worst-case images. However, the model-calculated TCP showed increasing differences from the ground truth as the complexity of the model increased [maximum difference of similar to 8% (model 3)], which could be attributed to the partial volume effect. Conclusions: Based on the results of this study, it is believed that simple techniques of biologically guided radiotherapy planning for lung cancer should be feasible at intermediate contrast levels (tumor-to-background ratio of similar to 10) with the clinically achievable image quality.

Introduction One method to overcome the problem of lung tumour movement in patients treated with radiotherapy is to restrict tumour motion with an active breathing control (ABC) device. This study evaluated the feasibility of using ABC in patients receiving radical radiotherapy for non-small cell lung cancer. Methods Eighteen patients, median (range) age of 66 (44–82) years, consented to the study. A training session was conducted to establish the patient’s breath hold level and breath hold time. Three planning scans were acquired using the ABC device. Reproducibility of breath hold was assessed by comparing lung volumes measured from the planning scans and the volume recorded by ABC. Patients were treated with a 3-field coplanar beam arrangement and treatment time (patient on and off the bed) and number of breath holds recorded. The tolerability of the device was assessed by weekly questionnaire. Quality assurance was performed on the two ABC devices used. Results 17/18 patients completed 32 fractions of radiotherapy using ABC. All patients tolerated a maximum breath hold time >15 s. The mean (SD) patient training time was 13.8 (4.8) min and no patient found the ABC very uncomfortable. Six to thirteen breath holds of 10–14 s were required per session. The mean treatment time was 15.8 min (5.8 min). The breath hold volumes were reproducible during treatment and also between the two ABC devices. Conclusion The use of ABC in patients receiving radical radiotherapy for NSCLC is feasible. It was not possible to predict a patient’s ability to hold breath. A minimum tolerated breath hold time of 15 s is recommended prior to commencing treatment.

Monte Carlo simulation is the gold standard method for modelling scattering processes in medical x-ray imaging. General-purpose Monte Carlo codes, however, typically use the independent atom approximation (IAA). This is known to be inaccurate for Rayleigh scattering, for many materials, in the forward direction. This work addresses whether the IAA is sufficient for the typical modelling tasks in medical kilovoltage x-ray imaging. As a means of comparison, we incorporate a more realistic 'interference function' model into a custom-written Monte Carlo code. First, we conduct simulations of scatter from isolated voxels of soft tissue, adipose, cortical bone and spongiosa. Then, we simulate scatter profiles from a cylinder of water and from phantoms of a patient's head, thorax and pelvis, constructed from diagnostic-quality CT data sets. Lastly, we reconstruct CT numbers from simulated sets of projection images and investigate the quantitative effects of the approximation. We show that the IAA can produce errors of several per cent of the total scatter, across a projection image, for typical x-ray beams and patients. The errors in reconstructed CT number, however, for the phantoms simulated, were small (typically < 10 HU). The IAA can therefore be considered sufficient for the modelling of scatter correction in CT imaging. Where accurate quantitative estimates of scatter in individual projection images are required, however, the appropriate interference functions should be included.

This work evaluates a three-dimensional (3D) freehand ultrasound-based localisation system with new probe pressure correction for use in partial breast irradiation. Accuracy and precision of absolute position measurement was measured as a function of imaging depth (ID), object depth, scanning direction and time using a water phantom containing crossed wires. To quantify the improvement in accuracy due to pressure correction, 3D scans of a breast phantom containing ball bearings were obtained with and without pressure. Ball bearing displacements were then measured with and without pressure correction. Using a single scan direction (for all imaging depths), the mean error was

The Large Area Sensor (LAS) is a 1350 times1350 array of active pixels on a 40 Im pitch fabricated in a 0.35 im CMOS process. Stitching technology is employed to achieve an area of 5.4 cm times5.4 cm. The sensor includes 'regions of reset', whereby three different integration times can be set on the array to achieve a large imaging range for static scenes. Characterization of the noise performance included temporal and fixed pattern sources. LAS was found to have a read noise of 62 e-, a full well capacity of 61 times103 e- and a conversion gain of 5 e- per digital number (DN). The fixed pattern noise (FPN) was evaluated at half saturation; within a single stitched section of the array, column-to-column FPN was found to be 0.6%, while the pixel-to-pixel FPN was 3%. Both FPN sources were found to be gain related and could be corrected via flat fielding. Based on the results of characterization, LAS was coupled to a structured CsI:Tl scintillator and included in an X-ray diffraction system developed for the analysis of breast biopsy samples. Data acquired with plastic test objects agrees with that acquired by a previous prototype sensor. It is demonstrated that an imaging output range of 140 dB can be achieved using integration times of 0.1 ms to record the transmitted X-ray beam and 2.3 s to record the lower intensity scattered radiation.

The technical feasibility and potential benefits of voxel-based nonuniform dose prescriptions for biologically heterogeneous tumors have been widely demonstrated. In some cases, an “ideal” dose prescription has been generated by individualizing the dose to every voxel within the target, but often this voxel-based prescription has been discretized into a small number of compartments. The number of dose levels utilized and the methods used for prescribing doses and assigning tumor voxels to different dose compartments have varied significantly. The authors present an investigation into the relationship between the complexity of the dose prescription and the tumor control probability TCP for a number of these methods. The linear quadratic model of cell killing was used in conjunction with a number of modeled tumors heterogeneous in clonogen density, oxygenation, or proliferation. Models based on simple mathematical functions, published biological data, and biological image data were investigated. Target voxels were assigned to dose compartments using i simple rules based on the initial biological distribution, ii iterative methods designed to maximize the achievable TCP, or iii methods based on an ideal dose prescription. The relative performance of the simple rules was found to depend on the form of heterogeneity of the tumor, while the iterative and ideal dose methods performed comparably for all models investigated. In all cases the maximum achievable TCP was approached within the first few typically two to five compartments. Results suggest that irrespective of the pattern of heterogeneity, the optimal dose prescription can be well approximated using only a few dose levels but only if both the compartment boundaries and prescribed dose levels are well chosen. © 2009 American Association of Physicists in Medicine. DOI: 10.1118/1.3213519