Preclinical investigation of the biomechanical properties of tissues and their treatment-induced changes are essential to support drug-discovery, clinical translation of biomarkers of treatment response, and studies of mechanobiology. Here we describe the first use of preclinical 3D elastography to map the shear wave speed (cs), which is related to tissue stiffness, in vivo and demonstrate the ability of our novel 3D vibrational shear wave elastography (3D-VSWE) system to detect tumour response to a therapeutic challenge. We investigate the use of one or two vibrational sources at vibrational frequencies of 700, 1000 and 1200 Hz. The within-subject coefficients of variation of our system were found to be excellent for 700 and 1000 Hz and 5.4 and 6.2%, respectively. The relative change in cs measured with our 3D-VSWE upon treatment with an anti-vascular therapy ZD6126 in two tumour xenografts reflected changes in tumour necrosis. U-87 MG drug vs vehicle: Δcs = −24.7 ± 2.5 % vs 7.5 ± 7.1%, (p = 0.002) and MDA-MB-231 drug vs vehicle: Δcs = −12.3 ± 2.7 % vs 4.5 ± 4.7%, (p = 0.02). Our system enables rapid (<5 min were required for a scan length of 15 mm and three vibrational frequencies) 3D mapping of quantitative tumour viscoelastic properties in vivo, allowing exploration of regional heterogeneity within tumours and speedy recovery of animals from anaesthesia so that longitudinal studies (e.g., during tumour growth or following treatment) may be conducted frequently..

Preclinical evaluation of novel therapies using models of cancer is an important tool in cancer research, where imaging can provide non-invasive tools to characterise the internal structure and function of tumours. The short propagation paths when imaging tumours and organs in small animals allow the use of high frequencies for both ultrasound and shear waves, providing the opportunity for high-resolution shear wave elastography and hence its use for studying the heterogeneity of tissue elasticity, where heterogeneity may be a predictor of tissue response. Here we demonstrate vibrational shear wave elastography (VSWE) using a mechanical actuator to produce high frequency (up to 1000 Hz) shear waves in preclinical tumours, an alternative to the majority of preclinical ultrasound SWE studies where an acoustic radiation force impulse is required to create a relatively low-frequency broad-band shear-wave pulse. We implement VSWE with a high frequency (17.8 MHz) probe running a focused line-by-line ultrasound imaging sequence which as expected was found to offer improved detection of 1000 Hz shear waves over an ultrafast planar wave imaging sequence in a homogenous tissue-mimicking phantom. We test the VSWE in anex vivotumour xenograft, demonstrating the ability to detect shear waves up to 10 mm from the contactor position at 1000 Hz. By reducing the kernel size used for shear wave speed estimation to 1 mm we are able to produce shear wave speed images with spatial resolution of this order. Finally, we present VSWE data from xenograft tumoursin vivo, demonstrating the feasibility of the technique in mice under isoflurane sedation. Mean shear wave speeds in the tumours are in good agreements with those reported by previous authors. Characterising the frequency dependence of shear wave speed demonstrates the potential to quantify the viscoelastic properties of tumoursin vivo..

In vivo ultrasound attenuation coefficient measurements are of interest as they can provide insight into tissue pathology. They are also needed so that measurements of the tissue's frequency dependent ultrasound backscattering coefficient may be corrected for attenuation. In vivo measurements of the attenuation coefficient are challenging because it has to be estimated from the depth dependent decay of backscatter signals that display a large degree of magnitude variation. In this study we describe and evaluate an improved backscatter method to estimate ultrasound attenuation which is tolerant to the presence of some backscatter inhomogeneity. This employs an automated algorithm to segment and remove atypically strong echoes to lessen the potential bias these may introduce on the attenuation coefficient estimates. The benefit of the algorithm was evaluated by measuring the frequency dependent attenuation coefficient of a gelatine phantom containing randomly distributed cellulose scatterers as a homogeneous backscattering component and planar pieces of cooked leek to provide backscattering inhomogeneities. In the phantom the segmentation algorithm was found to improve the accuracy and precision of attenuation coefficient estimates by up to 80% and 90%, respectively. The effect of the algorithm was then measured invivo using 32 radiofrequency B-mode datasets from the breasts of two healthy female volunteers, producing a 5 to 25% reduction in mean attenuation coefficient estimates and a 30 to 50% reduction in standard deviation of attenuation coefficient across different positions within each breast. The results suggest that the segmentation algorithm may improve the accuracy and precision of attenuation coefficient estimates invivo..

BACKGROUND: Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) therapy of pelvic tumors is currently assessed by visual estimation of the proportion of tumor that can be reached by the device's focus (coverage). Since it is important to assess whether enough energy reaches the tumor to achieve ablation, a methodology for estimating the proportion of the tumor that can be ablated (treatability) was developed. Predicted treatability was compared against clinically achieved thermal ablation. METHODS: MR Dixon sequence images of five patients with recurrent gynecological tumors were acquired during their treatment. Acousto-thermal simulations were performed using k-Wave for three exposure points (the deepest and shallowest reachable focal points within the tumor, identified from tumor coverage analysis, and a point halfway in-between) per patient. Interpolation between the resulting simulated ablated tissue volumes was used to estimate the maximum treatable depth and hence, tumor treatability. Predicted treatability was compared both to predicted tumor coverage and to the clinically treated tumor volume. The intended and simulated volumes and positions of ablated tissues were compared. RESULTS: Predicted treatability was less than coverage by 52% (range: 31-78%) of the tumor volume. Predicted and clinical treatability differed by 9% (range: 1-25%) of tumor volume. Ablated tissue volume and position varied with beam path length through tissue. CONCLUSION: Tumor coverage overestimated patient suitability for MRgHIFU therapy. Employing patient-specific simulations improved treatability assessment. Patient treatability assessment using simulations is feasible..

The stacked-ellipse (SE) algorithm was developed to rapidly segment the uterus on 3-D ultrasound (US) for the purpose of enabling US-guided adaptive radiotherapy (RT) for uterine cervix cancer patients. The algorithm was initialised manually on a single sagittal slice to provide a series of elliptical initialisation contours in semi-axial planes along the uterus. The elliptical initialisation contours were deformed according to US features such that they conformed to the uterine boundary. The uterus of 15 patients was scanned with 3-D US using the Clarity System (Elekta Ltd.) at multiple days during RT and manually contoured (n = 49 images and corresponding contours). The median (interquartile range) Dice similarity coefficient and mean surface-to-surface-distance between the SE algorithm and manual contours were 0.80 (0.03) and 3.3 (0.2) mm, respectively, which are within the ranges of reported inter-observer contouring variabilities. The SE algorithm could be implemented in adaptive RT to precisely segment the uterus on 3-D US..

BACKGROUND AND PURPOSE: Daily image guidance is standard care for prostate radiotherapy. Innovations which improve the accuracy and efficiency of ultrasound guidance are needed, particularly with respect to reducing interobserver variation. This study explores automation tools for this purpose, demonstrated on the Elekta Clarity Autoscan®. The study was conducted as part of the Clarity-Pro trial (NCT02388308). MATERIALS AND METHODS: Ultrasound scan volumes were collected from 32 patients. Prostate matches were performed using two proposed workflows and the results compared with Clarity's proprietary software. Gold standard matches derived from manually localised landmarks provided a reference. The two workflows incorporated a custom 3D image registration algorithm, which was benchmarked against a third-party application (Elastix). RESULTS: Significant reductions in match errors were reported from both workflows compared to standard protocol. Median (IQR) absolute errors in the left-right, anteroposterior and craniocaudal axes were lowest for the Manually Initiated workflow: 0.7(1.0) mm, 0.7(0.9) mm, 0.6(0.9) mm compared to 1.0(1.7) mm, 0.9(1.4) mm, 0.9(1.2) mm for Clarity. Median interobserver variation was ≪0.01 mm in all axes for both workflows compared to 2.2 mm, 1.7 mm, 1.5 mm for Clarity in left-right, anteroposterior and craniocaudal axes. Mean matching times was also reduced to 43 s from 152 s for Clarity. Inexperienced users of the proposed workflows attained better match precision than experienced users on Clarity. CONCLUSION: Automated image registration with effective input and verification steps should increase the efficacy of interfraction ultrasound guidance compared to the current commercially available tools..

BACKGROUND: Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) ablation of pelvic tumors is initially evaluated clinically for treatment feasibility using referral images, acquired using standard supine diagnostic imaging, followed by MR screening of potential patients lying on the MRgHIFU couch in a 'best-guess' treatment position. Existing evaluation methods result in ≥40% of referred patients being screened out because of tumor non-targetability. We hypothesize that this process could be improved by development of a novel algorithm for predicting tumor coverage from referral imaging. METHODS: The algorithm was developed from volunteer images and tested with patient data. MR images were acquired for five healthy volunteers and five patients with recurrent gynaecological cancer. Subjects were MR imaged supine and in oblique-supine-decubitus MRgHIFU treatment positions. Body outline and bones were segmented for all subjects, with organs-at-risk and tumors also segmented for patients. Supine images were aligned with treatment images to simulate a treatment dataset. Target coverage (of patient tumors and volunteer intra-pelvic soft tissue), i.e. the volume reachable by the MRgHIFU focus, was quantified. Target coverage predicted from supine imaging was compared to that from treatment imaging. RESULTS: Mean (±standard deviation) absolute difference between supine-predicted and treatment-predicted coverage for 5 volunteers was 9 ± 6% (range: 2-22%) and for 4 patients, was 12 ± 7% (range: 4-21%), excluding a patient with poor acoustic coupling (coverage difference was 53%). CONCLUSION: Prediction of MRgHIFU target coverage from referral imaging appears feasible, facilitating further development of automated evaluation of patient suitability for MRgHIFU..

AIMS: Irradiation of the internal mammary chain (IMC) is increasing following recently published data, but the need for formal delineation of lymph node volumes is slowing implementation in some healthcare settings. A field-placement algorithm for irradiating locoregional lymph nodes including the IMC could reduce the resource impact of introducing irradiation of the IMC. This study describes the development and evaluation of such an algorithm. MATERIALS AND METHODS: An algorithm was developed in which six points representing lymph node clinical target volume borders (based on European Society for Radiotherapy and Oncology consensus nodal contouring guidelines) were placed on computed tomography-defined anatomical landmarks and used to place tangential and nodal fields. Single-centre testing in 20 cases assessed the success of the algorithm in covering planning target volumes (PTVs) and adequately sparing organs at risk. Plans derived using the points algorithm were also compared with plans generated following formal delineation of nodal PTVs, using the Wilcoxon signed rank test. Timing data for point placement were collected. Multicentre testing using the same methods was then carried out to establish whether the technique was transferable to other centres. RESULTS: Single-centre testing showed that 95% of cases met the nodal PTV coverage dose constraints (binomial probability confidence interval 75.1-99.9%) with no statistically significant reduction in mean heart dose or ipsilateral lung V17Gy associated with formal nodal delineation. In multicentre testing, 69% of cases met nodal PTV dose constraints and there was a statistically significant difference in IMC PTV coverage using the points algorithm when compared with formally delineated nodal volumes (P < 0.01). However, there was no difference in axillary level 1-4 PTV coverage (P = 0.11) with all cases meeting target volume constraints. CONCLUSIONS: The optimal strategy for breast and locoregional lymph node radiotherapy is target volume delineation. However, use of this novel points-based field-placement algorithm results in dosimetrically acceptable plans without the need for formal lymph node contouring in a single-centre setting and for the breast and level 1-4 axilla in a multicentre setting. Further quality assurance measures are needed to enable implementation of the algorithm for irradiation of the IMC in a multicentre setting..

PURPOSE: Adaptive radiation therapy strategies could account for interfractional uterine motion observed in patients with cervix cancer, but the current cone beam computed tomography (CBCT)-based treatment workflow is limited by poor soft-tissue contrast. The goal of the present study was to determine if ultrasound (US) could be used to improve visualization of the uterus, either as a single modality or in combination with CBCT. METHODS AND MATERIALS: Interobserver uterine contour agreement and confidence were compared on 40 corresponding CBCT, US, and CBCT-US-fused images from 11 patients with cervix cancer. Contour agreement was measured using the Dice similarity coefficient (DSC) and mean contour-to-contour distance (MCCD). Observers rated their contour confidence on a scale from 1 to 10. Pairwise Wilcoxon signed-rank tests were used to measure differences in contour agreement and confidence. RESULTS: CBCT-US fused images had significantly better contour agreement and confidence than either individual modality (P < .05), with median (interquartile range [IQR]) values of 0.84 (0.11), 1.26 (0.23) mm, and 7 (2) for the DSC, MCCD, and observer confidence ratings, respectively. Contour agreement was similar between US and CBCT, with median (IQR) DSCs of 0.81 (0.17) and 0.82 (0.14) and MCCDs of 1.75 (1.15) mm and 1.62 (0.74) mm. Observers were significantly more confident in their US-based contours than in their CBCT-based contours (P < .05), with median (IQR) confidence ratings of 7 (2.75) versus 5 (4). CONCLUSIONS: CBCT and US are complementary and improve uterine segmentation precision when combined. Observers could localize the uterus with a similar precision on independent US and CBCT images..

BACKGROUND: Seroma describes a collection of serous fluid within a cavity, occurring following surgery. Seroma is associated with normal tissue effects (NTE) following breast radiotherapy, as reported by clinicians and on photographs. This study investigates the association between seroma and the NTE breast appearance change collected using patient-reported outcome measures (PROMs) in IMPORT HIGH, as well as investigating the association between breast appearance change and patient/tumour/treatment factors. METHODS: Case-control methodology was used for seroma analysis within IMPORT HIGH. Cases were patients reporting moderate/marked breast appearance change and controls reported none/mild changes at year-3. One control was selected at random for each case. Seromas were graded as not visible/subtle or visible/highly visible on CT radiotherapy planning scans. Logistic regression tested associations, adjusting for patient/tumour/treatment factors. RESULTS: 1078/1149 patients consented to PROMs, of whom 836 (78%) reported whether they had 3-year breast appearance change; 231 cases and 231 controls were identified. 304/462 (66%) patients received chemotherapy. Seroma prevalence was 20% (41/202) in cases and 16% (32/205) in controls, and less frequent in patients receiving adjuvant chemotherapy [10% (24/246) compared with 29% (40/138) without]. Visible seroma was not significantly associated with breast appearance change [OR 1.38 (95%CI 0.83-2.29), p = 0.219]. Larger tumour size, haematoma, current smoking and body image concerns at baseline were independent risk factors. CONCLUSIONS: Seroma was not associated with patient-reported breast appearance change, but haematoma and smoking were significant risk factors. Lack of association may be related to lower prevalence of seroma compared with previous reports, perhaps reflecting patients receiving adjuvant chemotherapy in whom seroma resolves prior to radiotherapy..

Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT..

Contrast enhanced ultrasound (CEUS) and dynamic contrast enhanced ultrasound (DCE-US) can be used to provide information about the vasculature aiding diagnosis and monitoring of a number of pathologies including cancer. In the development of a CEUS imaging system, there are many choices to be made, such as whether to use plane wave (PW) or focused imaging (FI), and the values for parameters such as transmit frequency, F-number, mechanical index, and number of compounding angles (for PW imaging). CEUS image contrast may also be dependent on subject characteristics, e.g. flow speed and vessel orientation. We evaluated the effect of such choices on vessel contrast for PW and FI in vitro, using 2D ultrasound imaging. CEUS images were obtained using a VantageTM (Verasonics Inc.) and a pulse-inversion (PI) algorithm on a flow phantom. Contrast (C) and contrast reduction (CR) were calculated, where C was the initial ratio of signal in vessel to signal in background and CR was its reduction after 200 frames (acquired in 20 s). Two transducer orientations were used: parallel and perpendicular to the vessel direction. Similar C and CR was achievable for PW and FI by choosing optimal parameter values. PW imaging suffered from high frequency grating lobe artefacts, which may lead to degraded image quality and misinterpretation of data. Flow rate influenced the contrast based on: (1) false contrast increase due to the bubble motion between the PI positive and negative pulses (for both PW and FI), and (2) contrast reduction due to the incoherency caused by bubble motion between the compounding angles (for PW only). The effects were less pronounced for perpendicular transducer orientation compared to a parallel one. Although both effects are undesirable, it may be more straight forward to account for artefacts in FI as it only suffers from the former effect. In conclusion, if higher frame rate imaging is not required (a benefit of PW), FI appears to be a better choice of imaging mode for CEUS, providing greater image quality over PW for similar rates of contrast reduction..

AIMS: Radiotherapy target volumes in early breast cancer treatment increasingly include the internal mammary chain (IMC). In order to maximise survival benefits of IMC radiotherapy, doses to the heart and lung should be minimised. This dosimetry study compared the ability of three-dimensional conformal radiotherapy, arc therapy and proton beam therapy (PBT) techniques with and without breath-hold to achieve target volume constraints while minimising dose to organs at risk (OARs). MATERIALS AND METHODS: In 14 patients' datasets, seven IMC radiotherapy techniques were compared: wide tangent (WT) three-dimensional conformal radiotherapy, volumetric-modulated arc therapy (VMAT) and PBT, each in voluntary deep inspiratory breath-hold (vDIBH) and free breathing (FB), and tomotherapy in FB only. Target volume coverage and OAR doses were measured for each technique. These were compared using a one-way ANOVA with all pairwise comparisons tested using Bonferroni's multiple comparisons test, with adjusted P-values ≤ 0.05 indicating statistical significance. RESULTS: One hundred per cent of WT(vDIBH), 43% of WT(FB), 100% of VMAT(vDIBH), 86% of VMAT(FB), 100% of tomotherapy FB and 100% of PBT plans in vDIBH and FB passed all mandatory constraints. However, coverage of the IMC with 90% of the prescribed dose was significantly better than all other techniques using VMAT(vDIBH), PBT(vDIBH) and PBT(FB) (mean IMC coverage ± 1 standard deviation = 96.0% ± 4.3, 99.8% ± 0.3 and 99.0% ± 0.2, respectively). The mean heart dose was significantly reduced in vDIBH compared with FB for both the WT (P < 0.0001) and VMAT (P < 0.0001) techniques. There was no advantage in target volume coverage or OAR doses for PBT(vDIBH) compared with PBT(FB). CONCLUSIONS: Simple WT radiotherapy delivered in vDIBH achieves satisfactory coverage of the IMC while meeting heart and lung dose constraints. However, where higher isodose coverage is required, VMAT(vDIBH) is the optimal photon technique. The lowest OAR doses are achieved by PBT, in which the use of vDIBH does not improve dose statistics..

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PURPOSE: Our purpose was to perform an in vivo validation of ultrasound imaging for intrafraction motion estimation using the Elekta Clarity Autoscan system during prostate radiation therapy. The study was conducted as part of the Clarity-Pro trial (NCT02388308). METHODS AND MATERIALS: Initial locations of intraprostatic fiducial markers were identified from cone beam computed tomography scans. Marker positions were translated according to Clarity intrafraction 3-dimensional prostate motion estimates. The updated locations were projected onto the 2-dimensional electronic portal imager plane. These Clarity-based estimates were compared with the actual portal-imaged 2-dimensional marker positions. Images from 16 patients encompassing 80 fractions were analyzed. To investigate the influence of intraprostatic markers and image quality on ultrasound motion estimation, 3 observers rated image quality, and the marker visibility on ultrasound images was assessed. RESULTS: The median difference between Clarity-defined intrafraction marker locations and portal-imaged marker locations was 0.6 mm (with 95% limit of agreement at 2.5 mm). Markers were identified on ultrasound in only 3 of a possible 240 instances. No linear relationship between image quality and Clarity motion estimation confidence was identified. The difference between Clarity-based motion estimates and electronic portal-imaged marker location was also independent of image quality. Clarity estimation confidence was degraded in a single fraction owing to poor probe placement. CONCLUSIONS: The accuracy of Clarity intrafraction prostate motion estimation is comparable with that of other motion-monitoring systems in radiation therapy. The effect of fiducial markers in the study was deemed negligible as they were rarely visible on ultrasound images compared with intrinsic anatomic features. Clarity motion estimation confidence was robust to variations in image quality and the number of ultrasound-imaged anatomic features; however, it was degraded as a result of poor probe placement..

PURPOSE: 3D ultrasound (US) images of the uterus may be used to adapt radiotherapy (RT) for cervical cancer patients based on changes in daily anatomy. This requires accurate on-line segmentation of the uterus. The aim of this work was to assess the accuracy of Elekta's "Assisted Gyne Segmentation" (AGS) algorithm in semi-automatically segmenting the uterus on 3D transabdominal ultrasound images by comparison with manual contours. MATERIALS & METHODS: Nine patients receiving RT for cervical cancer were imaged with the 3D Clarity® transabdominal probe at RT planning, and 1 to 7 times during treatment. Image quality was rated from unusable (0)-excellent (3). Four experts segmented the uterus (defined as the uterine body and cervix) manually and using AGS on images with a ranking > 0. Pairwise analysis between manual contours was evaluated to determine interobserver variability. The accuracy of the AGS method was assessed by measuring its agreement with manual contours via pairwise analysis. RESULTS: 35/44 images acquired (79.5%) received a ranking > 0. For the manual contour variation, the median [interquartile range (IQR)] distance between centroids (DC) was 5.41 [5.0] mm, the Dice similarity coefficient (DSC) was 0.78 [0.11], the mean surface-to-surface distance (MSSD) was 3.20 [1.8] mm, and the uniform margin of 95% (UM95) was 4.04 [5.8] mm. There was no correlation between image quality and manual contour agreement. AGS failed to give a result in 19.3% of cases. For the remaining cases, the level of agreement between AGS contours and manual contours depended on image quality. There were no significant differences between the AGS segmentations and the manual segmentations on the images that received a quality rating of 3. However, the AGS algorithm had significantly worse agreement with manual contours on images with quality ratings of 1 and 2 compared with the corresponding interobserver manual variation. The overall median [IQR] DC, DSC, MSSD, and UM95 between AGS and manual contours was 5.48 [5.45] mm, 0.77 [0.14], 3.62 [2.7] mm, and 5.19 [8.1] mm, respectively. CONCLUSIONS: The AGS tool was able to represent uterine shape of cervical cancer patients in agreement with manual contouring in cases where the image quality was excellent, but not in cases where image quality was degraded by common artifacts such as shadowing and signal attenuation. The AGS tool should be used with caution for adaptive RT purposes, as it is not reliable in accurately segmenting the uterus on 'good' or 'poor' quality images. The interobserver agreement between manual contours of the uterus drawn on 3D US was consistent with results of similar studies performed on CT and MRI images..

PURPOSE: The aim of this study was to estimate changes in surface dose due to the presence of the Clarity Autoscan™ ultrasound (US) probe during prostate radiotherapy using Monte Carlo (MC) methods. METHODS: MC models of the Autoscan US probe were developed using the BEAMnrc/DOSXYZnrc code based on kV and MV CT images. CT datasets were converted to voxelized mass density phantoms using a CT number-to-mass density calibration. The dosimetric effect of the probe, in the contact region (an 8 mm × 12 mm single layer of voxels), was investigated using a phantom set-up mimicking two scenarios (a) a transperineal imaging configuration (radiation beam perpendicular to the central US axial direction), and (b) a transabdominal imaging configuration (radiation beam parallel to the central US axial direction). For scenario (a), the dosimetric effect was evaluated as a function of the probe to inferior radiation field edge distance. Clinically applicable distances from 5 mm separation to 2 mm overlap were determined from the radiotherapy plans of 27 patients receiving Clarity imaging. Overlaps of 3 to 14 (1 to 3 SD) mm were also considered to include the effect of interfraction motion correction. The influence of voxel size on surface dose estimation was investigated. Approved clinical plans from two prostate patients were used to simulate worst-case dosimetric impact of the probe when large couch translations were applied to correct for interfraction prostate motion. RESULTS: The dosimetric impact of both the MV and kV probe models agreed within ±2% for both beam configurations. For scenario (a) and 1 mm voxel model, the probe gave mean dose increases of 1.2% to 4.6% (of the dose at isocenter) for 5 mm separation to 0 mm overlap in the probe-phantom contact region, respectively. This increased to 27.5% for the largest interfraction motion correction considered (14 mm overlap). For separations of ≥ 2 mm dose differences were < 2%. Simulated dose perturbations were found to be superficial; for the 14 mm overlap the dose increase reduced to < 3% at 5.0 mm within the phantom. For scenario (b), dose increases due to the probe were < 5% in all cases. The dose increase was underestimated by up to ~13% when the voxel size was increased from 1 mm to 3 mm. MC simulated dose to the PTV and OARs for the two clinical plans considered showed good agreement with commercial treatment planning system results (within 2%). Mean dose increases due to the presence of the probe, after the maximum interfraction motion correction, were ~16.3% and ~8.0%, in the contact region, for plan 1 and plan 2, respectively. CONCLUSIONS: The presence of the probe results in superficial dose perturbations for patients with an overlap between the probe and the radiation field present in either the original treatment plan or due to translation of the radiation field to simulate correction of interfraction internal prostate motion..

PURPOSE: Ultrasound-based motion estimation is an expanding subfield of image-guided radiation therapy. Although ultrasound can detect tissue motion that is a fraction of a millimeter, its accuracy is variable. For controlling linear accelerator tracking and gating, ultrasound motion estimates must remain highly accurate throughout the imaging sequence. This study presents a temporal regularization method for correlation-based template matching which aims to improve the accuracy of motion estimates. METHODS: Liver ultrasound sequences (15-23 Hz imaging rate, 2.5-5.5 min length) from ten healthy volunteers under free breathing were used. Anatomical features (blood vessels) in each sequence were manually annotated for comparison with normalized cross-correlation based template matching. Five sequences from a Siemens Acuson™ scanner were used for algorithm development (training set). Results from incremental tracking (IT) were compared with a temporal regularization method, which included a highly specific similarity metric and state observer, known as the α-β filter/similarity threshold (ABST). A further five sequences from an Elekta Clarity™ system were used for validation, without alteration of the tracking algorithm (validation set). RESULTS: Overall, the ABST method produced marked improvements in vessel tracking accuracy. For the training set, the mean and 95th percentile (95%) errors (defined as the difference from manual annotations) were 1.6 and 1.4 mm, respectively (compared to 6.2 and 9.1 mm, respectively, for IT). For each sequence, the use of the state observer leads to improvement in the 95% error. For the validation set, the mean and 95% errors for the ABST method were 0.8 and 1.5 mm, respectively. CONCLUSIONS: Ultrasound-based motion estimation has potential to monitor liver translation over long time periods with high accuracy. Nonrigid motion (strain) and the quality of the ultrasound data are likely to have an impact on tracking performance. A future study will investigate spatial uniformity of motion and its effect on the motion estimation errors..

BACKGROUND: Large breast size is associated with increased risk of late adverse effects after surgery and radiotherapy for early breast cancer. It is hypothesised that effects of radiotherapy on adipose tissue are responsible for some of the effects seen. In this study, the association of breast composition with late effects was investigated along with other breast features such as fibroglandular tissue distribution, seroma and scar. METHODS: The patient dataset comprised of 18 cases with changes in breast appearance at 2 years follow-up post-radiotherapy and 36 controls with no changes, from patients entered into the FAST-Pilot and UK FAST trials at The Royal Marsden. Breast composition, fibroglandular tissue distribution, seroma and scar were assessed on planning CT scan images and compared using univariate analysis. The association of all features with late-adverse effect was tested using logistic regression (adjusting for confounding factors) and matched analysis was performed using conditional logistic regression. RESULTS: In univariate analyses, no statistically significant differences were found between cases and controls in terms of breast features studied. A statistically significant association (p < 0.05) between amount of seroma and change in photographic breast appearance was found in unmatched and matched logistic regression analyses with odds ratio (95% CI) of 3.44 (1.28-9.21) and 2.57 (1.05-6.25), respectively. CONCLUSIONS: A significant association was found between seroma and late-adverse effects after radiotherapy although no significant associations were noted with breast composition in this study. Therefore, the cause for large breast size as a risk factor for late effects after surgery and optimally planned radiotherapy remains unresolved..

PURPOSE: To quantify the performance of the Clarity ultrasound (US) imaging system (Elekta AB, Stockholm, Sweden) for real-time dynamic multileaf collimator (MLC) tracking. METHODS: The Clarity calibration and quality assurance phantom was mounted on a motion platform moving with a periodic sine wave trajectory. The detected position of a 30 mm hypoechogenic sphere within the phantom was continuously reported via Clarity's real-time streaming interface to an in-house tracking and delivery software and subsequently used to adapt the MLC aperture. A portal imager measured MV treatment field/MLC apertures and motion platform positions throughout each experiment to independently quantify system latency and geometric error. Based on the measured range of latency values, a prostate stereotactic body radiation therapy (SBRT) delivery was performed with three realistic motion trajectories. The dosimetric impact of system latency on MLC tracking was directly measured using a 3D dosimeter mounted on the motion platform. RESULTS: For 2D US imaging, the overall system latency, including all delay times from the imaging and delivery chain, ranged from 392 to 424 ms depending on the lateral sector size. For 3D US imaging, the latency ranged from 566 to 1031 ms depending on the elevational sweep. The latency-corrected geometric root-mean squared error was below 0.75 mm (2D US) and below 1.75 mm (3D US). For the prostate SBRT delivery, the impact of a range of system latencies (400-1000 ms) on the MLC tracking performance was minimal in terms of gamma failure rate. CONCLUSIONS: Real-time MLC tracking based on a noninvasive US input is technologically feasible. Current system latencies are higher than those for x-ray imaging systems, but US can provide full volumetric image data and the impact of system latency was measured to be small for a prostate SBRT case when using a US-like motion input..

BACKGROUND: Accurate segmentation of breast tissues is required for a number of applications such as model based deformable registration in breast radiotherapy. The accuracy of breast tissue segmentation is affected by the spatial distribution (or pattern) of fibroglandular tissue (FT). The goal of this study was to develop and evaluate texture features, determined from planning computed tomography (CT) data, to classify the spatial distribution of FT in the breast. METHODS: Planning CT data of 23 patients were evaluated in this study. Texture features were derived from the radial glandular fraction (RGF), which described the distribution of FT within three breast regions (posterior, middle, and anterior). Using visual assessment, experts grouped patients according to FT spatial distribution: sparse or non-sparse. Differences in the features between the two groups were investigated using the Wilcoxon rank test. Classification performance of the features was evaluated for a range of support vector machine (SVM) classifiers. RESULTS: Experts found eight patients and 15 patients had sparse and non-sparse spatial distribution of FT, respectively. A large proportion of features (>9 of 13) from the individual breast regions had significant differences (p <0.05) between the sparse and non-sparse group. The features from middle region had most significant differences and gave the highest classification accuracy for all the SVM kernels investigated. Overall, the features from middle breast region achieved highest accuracy (91%) with the linear SVM kernel. CONCLUSION: This study found that features based on radial glandular fraction provide a means for discriminating between fibroglandular tissue distributions and could achieve a classification accuracy of 91%..

Imaging has become an essential tool in modern radiotherapy (RT), being used to plan dose delivery prior to treatment and verify target position before and during treatment. Ultrasound (US) imaging is cost-effective in providing excellent contrast at high resolution for depicting soft tissue targets apart from those shielded by the lungs or cranium. As a result, it is increasingly used in RT setup verification for the measurement of inter-fraction motion, the subject of Part I of this review (Fontanarosa et al 2015 Phys. Med. Biol. 60 R77-114). The combination of rapid imaging and zero ionising radiation dose makes US highly suitable for estimating intra-fraction motion. The current paper (Part II of the review) covers this topic. The basic technology for US motion estimation, and its current clinical application to the prostate, is described here, along with recent developments in robust motion-estimation algorithms, and three dimensional (3D) imaging. Together, these are likely to drive an increase in the number of future clinical studies and the range of cancer sites in which US motion management is applied. Also reviewed are selections of existing and proposed novel applications of US imaging to RT. These are driven by exciting developments in structural, functional and molecular US imaging and analytical techniques such as backscatter tissue analysis, elastography, photoacoustography, contrast-specific imaging, dynamic contrast analysis, microvascular and super-resolution imaging, and targeted microbubbles. Such techniques show promise for predicting and measuring the outcome of RT, quantifying normal tissue toxicity, improving tumour definition and defining a biological target volume that describes radiation sensitive regions of the tumour. US offers easy, low cost and efficient integration of these techniques into the RT workflow. US contrast technology also has potential to be used actively to assist RT by manipulating the tumour cell environment and by improving the delivery of radiosensitising agents. Finally, US imaging offers various ways to measure dose in 3D. If technical problems can be overcome, these hold potential for wide-dissemination of cost-effective pre-treatment dose verification and in vivo dose monitoring methods. It is concluded that US imaging could eventually contribute to all aspects of the RT workflow..

OBJECTIVE: To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT). METHODS: Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated. RESULTS: For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone. CONCLUSION: If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility. ADVANCES IN KNOWLEDGE: Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others..

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In modern radiotherapy, verification of the treatment to ensure the target receives the prescribed dose and normal tissues are optimally spared has become essential. Several forms of image guidance are available for this purpose. The most commonly used forms of image guidance are based on kilovolt or megavolt x-ray imaging. Image guidance can also be performed with non-harmful ultrasound (US) waves. This increasingly used technique has the potential to offer both anatomical and functional information.This review presents an overview of the historical and current use of two-dimensional and three-dimensional US imaging for treatment verification in radiotherapy. The US technology and the implementation in the radiotherapy workflow are described. The use of US guidance in the treatment planning process is discussed. The role of US technology in inter-fraction motion monitoring and management is explained, and clinical studies of applications in areas such as the pelvis, abdomen and breast are reviewed. A companion review paper (O'Shea et al 2015 Phys. Med. Biol. submitted) will extensively discuss the use of US imaging for intra-fraction motion quantification and novel applications of US technology to RT..

OBJECTIVE: Cone beam CT (CBCT) enables soft-tissue registration to planning CT for position verification in radiotherapy. The aim of this study was to determine the interobserver error (IOE) in prostate position verification using a standard CBCT protocol, and the effect of reducing CBCT scan length or increasing exposure, compared with standard imaging protocol. METHODS: CBCT images were acquired using a novel 7 cm length image with standard exposure (1644 mAs) at Fraction 1 (7), standard 12 cm length image (1644 mAs) at Fraction 2 (12) and a 7 cm length image with higher exposure (2632 mAs) at Fraction 3 (7H) on 31 patients receiving radiotherapy for prostate cancer. Eight observers (two clinicians and six radiographers) registered the images. Guidelines and training were provided. The means of the IOEs were compared using a Kruzkal-Wallis test. Levene's test was used to test for differences in the variances of the IOEs and the independent prostate position. RESULTS: No significant difference was found between the IOEs of each image protocol in any direction. Mean absolute IOE was the greatest in the anteroposterior direction. Standard deviation (SD) of the IOE was the least in the left-right direction for each of the three image protocols. The SD of the IOE was significantly less than the independent prostate motion in the anterior-posterior (AP) direction only (1.8 and 3.0 mm, respectively: p = 0.017). IOEs were within 1 SD of the independent prostate motion in 95%, 77% and 96% of the images in the RL, SI and AP direction. CONCLUSION: Reducing CBCT scan length and increasing exposure did not have a significant effect on IOEs. To reduce imaging dose, a reduction in CBCT scan length could be considered without increasing the uncertainty in prostate registration. Precision of CBCT verification of prostate radiotherapy is affected by IOE and should be quantified prior to implementation. ADVANCES IN KNOWLEDGE: This study shows the importance of quantifying the magnitude of IOEs prior to CBCT implementation..

PURPOSE: There is substantial observer variability in the delineation of target volumes for post-surgical partial breast radiotherapy because the tumour bed has poor x-ray contrast. This variability may result in substantial variations in planned dose distribution. Ultrasound elastography (USE) has an ability to detect mechanical discontinuities and therefore, the potential to image the scar and distortion in breast tissue architecture. The goal of this study was to compare USE techniques: strain elastography (SE), shear wave elastography (SWE) and acoustic radiation force impulse (ARFI) imaging using phantoms that simulate features of the tumour bed, for the purpose of incorporating USE in breast radiotherapy planning. METHODS: Three gelatine-based phantoms (10% w/v) containing: a stiff inclusion (gelatine 16% w/v) with adhered boundaries, a stiff inclusion (gelatine 16% w/v) with mobile boundaries and fluid cavity inclusion (to mimic seroma), were constructed and used to investigate the USE techniques. The accuracy of the elastography techniques was quantified by comparing the imaged inclusion with the modelled ground-truth using the Dice similarity coefficient (DSC). For two regions of interest (ROI), the DSC measures their spatial overlap. Ground-truth ROIs were modelled using geometrical measurements from B-mode images. RESULTS: The phantoms simulating stiff scar tissue with adhered and mobile boundaries and seroma were successfully developed and imaged using SE and SWE. The edges of the stiff inclusions were more clearly visible in SE than in SWE. Subsequently, for all these phantoms the measured DSCs were found to be higher for SE (DSCs: 0.91-0.97) than SWE (DSCs: 0.68-0.79) with an average relative difference of 23%. In the case of seroma phantom, DSC values for SE and SWE were similar. CONCLUSION: This study presents a first attempt to identify the most suitable elastography technique for use in breast radiotherapy planning. Further analysis will include comparison of ARFI with SE and SWE. This work is supported by the EPSRC Platform Grant, reference number EP/H046526/1..

PURPOSE: This study investigates the use of a mechanically swept 3D ultrasound (US) probe to estimate intra-fraction motion of the prostate during radiation therapy using an US phantom and simulated transperineal imaging. METHODS: A 3D motion platform was used to translate an US speckle phantom while simulating transperineal US imaging. Motion patterns for five representative types of prostate motion, generated from patient data previously acquired with a Calypso system, were using to move the phantom in 3D. The phantom was also implanted with fiducial markers and subsequently tracked using the CyberKnife kV x-ray system for comparison. A normalised cross correlation block matching algorithm was used to track speckle patterns in 3D and 2D US data. Motion estimation results were compared with known phantom translations. RESULTS: Transperineal 3D US could track superior-inferior (axial) and anterior-posterior (lateral) motion to better than 0.8 mm root-mean-square error (RMSE) at a volume rate of 1.7 Hz (comparable with kV x-ray tracking RMSE). Motion estimation accuracy was poorest along the US probe's swept axis (right-left; RL; RMSE < 4.2 mm) but simple regularisation methods could be used to improve RMSE (< 2 mm). 2D US was found to be feasible for slowly varying motion (RMSE < 0.5 mm). 3D US could also allow accurate radiation beam gating with displacement thresholds of 2 mm and 5 mm exhibiting a RMSE of less than 0.5 mm. CONCLUSION: 2D and 3D US speckle tracking is feasible for prostate motion estimation during radiation delivery. Since RL prostate motion is small in magnitude and frequency, 2D or a hybrid (2D/3D) US imaging approach which also accounts for potential prostate rotations could be used. Regularisation methods could be used to ensure the accuracy of tracking data, making US a feasible approach for gating or tracking in standard or hypo-fractionated prostate treatments..

PURPOSE: In breast radiotherapy, the target volume may change during treatment and need adaptation of the treatment plan. This is possible for both tumour bed (TB) and whole breast (WB) target volumes. Delineation of the target (to detect changes) is also subject to uncertainty due to intra- and inter-observer variability. This work measured the uncertainty, due to intraobserver variability, in the quantification of tissue deformation. METHODS: Datasets consisting of paired prone and supine CT scans of three patients were used. Significant deformation in target volumes is expected between prone and supine patient positions. The selected cases had 1) no seroma, 2) some seroma, and 3) large seroma. The TB and WB were outlined on each dataset three times by one clinician. Delineation variability was defined as the standard deviations of the distances between observer outlines. For each target volume and each case, tissue deformation between prone and supine delineations was quantified using the Dice similarity coefficient (DSC) and the average surface distance (ASD). The uncertainty in the tissue deformation (due to delineation variability) was quantified by measuring the ranges of DSC and ASD using all combinations of pairs of outlines (9 pairs). RESULTS: For the TB, the range of delineation variability was 0.44-1.16 mm. The deformation, DSC and ASD, (and uncertainty in measurement) of the TB between prone and supine position of the cases were: 1) 0.21 (0.17-0.28) and 12.4 mm (11.8-13 mm); 2) 0.54 (0.51-0.57) and 3.3 mm (3.1-3.5 mm); 3) 0.62 (0.61-0.64) and 4.9 mm (4.6-5.2 mm). WB deformation measurements were subject to less uncertainty due to delineation variability than TB deformation measurements. CONCLUSION: For the first time, the uncertainty, due to observer variability, in the measurement of the deformation of breast target volumes was investigated. Deformations in these ranges would be difficult to detect. This work was supported in part by Cancer Research-UK under Programme Grant C46/A10588 and in part by the National Institute for Health Research (NIHR) through funding of the biomedical research imaging centre. P. Juneja is supported by the EPSRC Platform Grant EP/H046526/1..

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 <2.0 mm) using a correlation threshold in the ultrasound tracking code to remove erroneous inter-volume displacement estimates. Mechanically-swept 3D-US can track the major components of intra-fraction prostate motion accurately but exhibits some limitations. The largest US RMSE was for elevational (RL) motion. For the AP and SI axes, accuracy was sub-millimetre. It may be feasible to track prostate motion in 2D only. 3D-US also has the potential to improve high tracking accuracy for all motion types. It would be advisable to use US in conjunction with a small (∼2.0 mm) centre-of-mass displacement threshold in which case it would be possible to take full advantage of the accuracy and high imaging rate capability..

AIMS: To determine the effect of image-guided radiotherapy on the dose distributions in breast boost treatments. MATERIALS AND METHODS: 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. RESULTS: 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 was <95% (>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. CONCLUSIONS: 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..

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Background

Whole-breast radiotherapy (WBRT) is the standard treatment for breast cancer following breast-conserving surgery. Evidence shows that tumour recurrences occur near the original cancer: the tumour bed. New treatment developments include increasing dose to the tumour bed during WBRT (synchronous integrated boost) and irradiating only the region around the tumour bed, for patients at high and low risk of tumour recurrence, respectively. Currently, standard imaging uses bony anatomy to ensure accurate delivery of WBRT. It is debatable whether or not more targeted treatments such as synchronous integrated boost and partial-breast radiotherapy require image-guided radiotherapy (IGRT) focusing on implanted tumour bed clips (clip-based IGRT).

Objectives

Primary – to compare accuracy of patient set-up using standard imaging compared with clip-based IGRT. Secondary – comparison of imaging techniques using (1) tumour bed radiotherapy safety margins, (2) volume of breast tissue irradiated around tumour bed, (3) estimated breast toxicity following development of a normal tissue control probability model and (4) time taken.

Design

Multicentre observational study embedded within a national randomised trial: IMPORT-HIGH (Intensity Modulated and Partial Organ Radiotherapy – HIGHer-risk patient group) testing synchronous integrated boost and using clip-based IGRT.

Setting

Five radiotherapy departments, participating in IMPORT-HIGH.

Participants

Two-hundred and eighteen patients receiving breast radiotherapy within IMPORT-HIGH.

Interventions

There was no direct intervention in patients’ treatment. Experimental and control intervention were clip-based IGRT and standard imaging, respectively. IMPORT-HIGH patients received clip-based IGRT as routine; standard imaging data were obtained from clip-based IGRT images.

Main outcome measures

Difference in (1) set-up errors, (2) safety margins, (3) volume of breast tissue irradiated, (4) breast toxicity and (5) time, between clip-based IGRT and standard imaging.

Results

The primary outcome of overall mean difference in clip-based IGRT and standard imaging using daily set-up errors was 2–2.6 mm (p < 0.001). Heterogeneity testing between centres found a statistically significant difference in set-up errors at one centre. For four centres (179 patients), clip-based IGRT gave a mean decrease in the systematic set-up error of between 1 mm and 2 mm compared with standard imaging. Secondary outcomes were as follows: clip-based IGRT and standard imaging safety margins were less than 5 mm and 8 mm, respectively. Using clip-based IGRT, the median volume of tissue receiving 95% of prescribed boost dose decreased by 29 cm3 (range 11–193 cm3) compared with standard imaging. Difference in median time required to perform clip-based IGRT compared with standard imaging was X-ray imaging technique dependent (range 8–76 seconds). It was not possible to estimate differences in breast toxicity, the normal tissue control probability model indicated that for breast fibrosis maximum radiotherapy dose is more important than volume of tissue irradiated.

Conclusions and implications for clinical practice

Margins of less than 8 mm cannot be used safely without clip-based IGRT for patients receiving concomitant tumour bed boost, as there is a risk of geographical miss of the tumour bed being treated. In principle, smaller but accurately placed margins may influence local control and toxicity rates, but this needs to be evaluated from mature clinical trial data in the future.

Funding

This project is/was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership..

PURPOSE: International consensus has not been reached regarding the optimal number of implanted tumour bed (TB) markers for partial breast/breast boost radiotherapy target volume delineation. Four common methods are: insertion of 6 clips (4 radial, 1 deep and 1 superficial), 5 clips (4 radial and 1 deep), 1 clip at the chest wall, and no clips. We compared TB volumes delineated using 6, 5, 1 and 0 clips in women who have undergone wide-local excision (WLE) of breast cancer (BC) with full-thickness closure of the excision cavity, in order to determine the additional margin required for breast boost or partial breast irradiation (PBI) when fewer than 6 clips are used. METHODS: Ten patients with invasive ductal BC who had undergone WLE followed by implantation of six fiducial markers (titanium clips) each underwent CT imaging for radiotherapy planning purposes. Retrospective processing of the DICOM image datasets was performed to remove markers and associated imaging artefacts, using an in-house software algorithm. Four observers outlined TB volumes on four different datasets for each case: (1) all markers present (CT6M); (2) the superficial marker removed (CT(5M)); (3) all but the chest wall marker removed (CTCW); (4) all markers removed (CT(0M)). For each observer, the additional margin required around each of TB(0M), TBCW, and TB(5M) in order to encompass TB(6M) was calculated. The conformity level index (CLI) and differences in centre-of-mass (COM) between observers were quantified for CT(0M), CTCW, CT(5M), CT(6M). RESULTS: The overall median additional margins required to encompass TB(6M) were 8mm (range 0-28 mm) for TB(0M), 5mm (range 1-13 mm) for TBCW, and 2mm (range 0-7 mm) for TB(5M). CLI were higher for TB volumes delineated using CT(6M) (0.31) CT(5M) (0.32) than for CTCW (0.19) and CT(0M) (0.15). CONCLUSIONS: In women who have undergone WLE of breast cancer with full-thickness closure of the excision cavity and who are proceeding to PBI or breast boost RT, target volume delineation based on 0 or 1 implanted markers is not recommended as large additional margins are required to account for uncertainty over true TB location. Five implanted markers (one deep and four radial) are likely to be adequate assuming the addition of a standard 10-15 mm TB-CTV margin. Low CLI values for all TB volumes reflect the sensitivity of low volumes to small differences in delineation and are unlikely to be clinically significant for TB(5M) and TB(6M) in the context of adequate TB-CTV margins..

Validation is required to ensure automated segmentation algorithms are suitable for radiotherapy target definition. In the absence of true segmentation, algorithmic segmentation is validated against expert outlining of the region of interest. Multiple experts are used to overcome inter-expert variability. Several approaches have been studied in the literature, but the most appropriate approach to combine the information from multiple expert outlines, to give a single metric for validation, is unclear. None consider a metric that can be tailored to case-specific requirements in radiotherapy planning. Validation index (VI), a new validation metric which uses experts' level of agreement was developed. A control parameter was introduced for the validation of segmentations required for different radiotherapy scenarios: for targets close to organs-at-risk and for difficult to discern targets, where large variation between experts is expected. VI was evaluated using two simulated idealized cases and data from two clinical studies. VI was compared with the commonly used Dice similarity coefficient (DSCpair - wise) and found to be more sensitive than the DSCpair - wise to the changes in agreement between experts. VI was shown to be adaptable to specific radiotherapy planning scenarios..

INTRODUCTION: The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. MATERIALS AND METHODS: We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models. RESULTS: 26.8% patients in the Cambridge trial (5years) and 20.7% patients in the EORTC trial (10years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. CONCLUSIONS: This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis..

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..

PURPOSE: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. METHODS AND MATERIALS: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. RESULTS: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. CONCLUSIONS: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue segmentation methods should be used with caution in patients with sparse fibroglandular tissue distribution..

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 ∼10 mm, is possible with zero imaging dose and workload, however, patients receiving boost radiotherapy may benefit from a margin reduction of ∼4 mm 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..

The effectiveness of intensity-modulated radiation therapy (IMRT) is compromised by involuntary motion (e.g. respiration, cardiac activity). The feasibility of processing ultrasound echo data to automatically estimate 3D liver motion for real-time IMRT guidance was previously demonstrated, but performance was limited by an acquisition speed of 2 volumes per second due to hardware restrictions of a mechanical linear array probe. Utilizing a 2D matrix array probe with parallel receive beamforming offered increased acquisition speeds and an opportunity to investigate the benefits of higher volume rates. In vivo livers of three volunteers were scanned with and without respiratory motion at volume rates of 24 and 48 Hz, respectively. Respiration was suspended via voluntary breath hold. Correlation-based, phase-sensitive 3D speckle tracking was applied to consecutively acquired volumes of echo data. Volumes were omitted at fixed intervals and 3D speckle tracking was re-applied to study the effect of lower scan rates. Results revealed periodic motion that corresponded with the heart rate or breathing cycle in the absence or presence of respiration, respectively. For cardiac-induced motion, volume rates for adequate tracking ranged from 8 to 12 Hz and was limited by frequency discrepancies between tracking estimates from higher and lower frequency scan rates. Thus, the scan rate of volume data acquired without respiration was limited by the need to sample the frequency induced by the beating heart. In respiratory-dominated motion, volume rate limits ranged from 4 to 12 Hz, interpretable from the root-mean-squared deviation (RMSD) from tracking estimates at 24 Hz. While higher volume rates yielded RMSD values less than 1 mm in most cases, lower volume rates yielded RMSD values of 2-6 mm..

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BACKGROUND AND PURPOSE: We describe a feasibility study testing the use of gold seeds for the identification of post-operative tumour bed after breast conservation surgery (BCS). MATERIALS AND METHODS: Fifty-three patients undergoing BCS for invasive cancer were recruited. Successful use was defined as all six seeds correctly positioned around the tumour bed during BCS, unique identification of all implanted seeds on CT planning scan and ≥ 3 seeds uniquely identified at verification to give couch displacement co-ordinates in 10/15 fractions. Planning target volume (PTV) margin size for four correction strategies were calculated from these data. Variability in tumour bed contouring was investigated with five radiation oncologists outlining five CT datasets. RESULTS: Success in inserting gold seeds, identifying them at CT planning and using them for on-treatment verification was recorded in 45/51 (88%), 37/38 (97%) and 42/43 (98%) of patients, respectively. The clinicians unfamiliar with CT breast planning consistently contoured larger volumes than those already trained. Margin size ranged from 10.1 to 1.4mm depending on correction strategy. CONCLUSION: It is feasible to implant tumour bed gold seeds during BCS. Whilst taking longer to insert than surgical clips, they have the advantage of visibility for outlining and verification regardless of the ionising radiation beam quality. Appropriate correction strategies enable margins of the order of 5mm as required by the IMPORT trials however, tackling clinician variability in contouring is important..

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 μm. 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..

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..

BACKGROUND AND PURPOSE: To compare partial-breast clinical target volumes generated using a standard 15 mm margin (CTV(standard)) with those generated using three-dimensional surgical excision margins (CTV(tailored 30)) in women who have undergone wide local excision (WLE) for breast cancer. MATERIAL AND METHODS: Thirty-five women underwent WLE with placement of clips in the anterior, deep and coronal excision cavity walls. Distances from tumour to each of six margins were measured microscopically. Tumour bed was defined on kV-CT images using clips. CTV(standard) was generated by adding a uniform three-dimensional 15 mm margin, and CTV(tailored 30) was generated by adding 30 mm minus the excision margin in three-dimensions. Concordance between CTV(standard) and CTV(tailored 30) was quantified using conformity (CoI), geographical-miss (GMI) and normal-tissue (NTI) indices. An external-beam partial-breast irradiation (PBI) plan was generated to cover 95% of CTV(standard) with the 95% isodose. Percentage-volume coverage of CTV(tailored 30) by the 95% isodose was measured. RESULTS: Median (range) coronal, superficial and deep excision margins were 15.0 (0.5-76.0)mm, 4.0 (0.0-60.0)mm and 4.0 (0.5-35.0)mm, respectively. Median CoI, GMI and NTI were 0.62, 0.16 and 0.20, respectively. Median coverage of CTV(tailored 30) by the PBI-plan was 97.7% (range 84.9-100.0%). CTV(tailored 30) was inadequately covered by the 95% isodose in 4/29 cases. In three cases, the excision margin in the direction of inadequate coverage was

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We have evaluated a 4D ultrasound-based motion tracking system developed for tracking of abdominal organs during therapy. Tracking accuracy and precision were determined using a tissue-mimicking phantom, by comparing tracked motion with known 3D sinusoidal motion. The feasibility of tracking 3D liver motion in vivo was evaluated by acquiring 4D ultrasound data from four healthy volunteers. For two of these volunteers, data were also acquired whilst simultaneously measuring breath flow using a spirometer. Hepatic blood vessels, tracked off-line using manual tracking, were used as a reference to assess, in vivo, two types of automated tracking algorithm: incremental (from one volume to the next) and non-incremental (from the first volume to each subsequent volume). For phantom-based experiments, accuracy and precision (RMS error and SD) were found to be 0.78 mm and 0.54 mm, respectively. For in vivo measurements, mean absolute distance and standard deviation of the difference between automatically and manually tracked displacements were less than 1.7 mm and 1 mm respectively in all directions (left-right, anterior-posterior and superior-inferior). In vivo non-incremental tracking gave the best agreement. In both phantom and in vivo experiments, tracking performance was poorest for the elevational component of 3D motion. Good agreement between automatically and manually tracked displacements indicates that 4D ultrasound-based motion tracking has potential for image guidance applications in therapy..

PURPOSE: To determine target volume changes by using volume and shape analysis for patients receiving radiotherapy after breast conservation surgery and to compare different methods of automatically identifying changes in target volume, position, size, and shape during radiotherapy for use in adaptive radiotherapy. METHODS AND MATERIALS: Eleven patients undergoing whole breast radiotherapy had fiducial markers sutured into the excision cavity at the time of surgery. Patients underwent imaging using computed tomography (for planning and at the end of treatment) and during treatment by using portal imaging. A marker volume (MV) was defined by using the measured marker positions. Changes in both individual marker positions and MVs were identified manually and using six automated similarity indices. Comparison of the two types of analysis (manual and automated) was undertaken to establish whether similarity indices can be used to automatically detect changes in target volumes. RESULTS: Manual analysis showed that 3 patients had significant MV reduction. This analysis also showed significant changes between planning computed tomography and the start of treatment for 9 patients, including single and multiple marker movement, deformation (shape change), and rotation. Four of the six similarity indices were shown to be sensitive to the observed changes. CONCLUSIONS: Significant changes in size, shape, and position occur to the fiducial marker-defined volume. Four similarity indices can be used to identify these changes, and a protocol for their use in adaptive radiotherapy is suggested..

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 <1.3 mm, with the exception of the wires at 68.5 mm imaged with an ID of 85 mm, which gave a mean error of -2.3 mm. Precision was greater than 1 mm for any single scan direction. For multiple scan directions, precision was within 1.7 mm. Probe pressure corrections of between 0 mm and 2.2 mm have been observed for pressure displacements of 1.1 mm to 4.2 mm. Overall, anteroposterior position measurement accuracy increased from 2.2 mm to 1.6 mm and to 1.4 mm for the two opposing scanning directions. Precision is comparable to that reported for other commercially available ultrasound localisation systems, provided that 3D image acquisition is performed in the same scan direction. The existing temporal calibration is imperfect and a "per installation" calibration would further improve the accuracy and precision. Probe pressure correction was shown to improve the accuracy and will be useful for the localisation of the excision cavity in partial breast radiotherapy..

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PURPOSE: To evaluate the utility of intraprostatic markers in the treatment verification of prostate cancer radiotherapy. Specific aims were: to compare the effectiveness of offline correction protocols, either using gold markers or bony anatomy; to estimate the potential benefit of online correction protocol's using gold markers; to determine the presence and effect of intrafraction motion. METHODS AND MATERIALS: Thirty patients with three gold markers inserted had pretreatment and posttreatment images acquired and were treated using an offline correction protocol and gold markers. Retrospectively, an offline protocol was applied using bony anatomy and an online protocol using gold markers. RESULTS: The systematic errors were reduced from 1.3, 1.9, and 2.5 mm to 1.1, 1.1, and 1.5 mm in the right-left (RL), superoinferior (SI), and anteroposterior (AP) directions, respectively, using the offline correction protocol and gold markers instead of bony anatomy. The subsequent decrease in margins was 1.7, 3.3, and 4 mm in the RL, SI, and AP directions, respectively. An offline correction protocol combined with an online correction protocol in the first four fractions reduced random errors further to 0.9, 1.1, and 1.0 mm in the RL, SI, and AP directions, respectively. A daily online protocol reduced all errors to <1 mm. Intrafraction motion had greater impact on the effectiveness of the online protocol than the offline protocols. CONCLUSIONS: An offline protocol using gold markers is effective in reducing the systematic error. The value of online protocols is reduced by intrafraction motion..

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Three-dimensional (3D) soft tissue tracking is of interest for monitoring organ motion during therapy. Our goal is to assess the tracking performance of a curvilinear 3D ultrasound probe in terms of the accuracy and precision of measured displacements. The first aim was to examine the depth dependence of the tracking performance. This is of interest because the spatial resolution varies with distance from the elevational focus and because the curvilinear geometry of the transducer causes the spatial sampling frequency to decrease with depth. Our second aim was to assess tracking performance as a function of the spatial sampling setting (low, medium or high sampling). These settings are incorporated onto 3D ultrasound machines to allow the user to control the trade-off between spatial sampling and temporal resolution. Volume images of a speckle-producing phantom were acquired before and after the probe had been moved by a known displacement (1, 2 or 8 mm). This allowed us to assess the optimum performance of the tracking algorithm, in the absence of motion. 3D speckle tracking was performed using 3D cross-correlation and sub-voxel displacements were estimated. The tracking performance was found to be best for axial displacements and poorest for elevational displacements. In general, the performance decreased with depth, although the nature of the depth dependence was complex. Under certain conditions, the tracking performance was sufficient to be useful for monitoring organ motion. For example, at the highest sampling setting, for a 2 mm displacement, good accuracy and precision (an error and standard deviation of <0.4 mm) were observed at all depths and for all directions of displacement. The trade-off between spatial sampling, temporal resolution and size of the field of view (FOV) is discussed..

A new model of the light output from single-crystal scintillators in megavoltage energy x-ray beams has been developed, based on the concept of a Lambertian light guide model (LLG). This was evaluated in comparison with a Monte Carlo (MC) model of optical photon transport, previously developed and reported in the literature, which was used as a gold standard. The LLG model was developed to enable optimization of scintillator detector design. In both models the dose deposition and light propagation were decoupled, the scintillators were cuboids, split into a series of cells as a function of depth, with Lambertian side and entrance faces, and a specular exit face. The signal in a sensor placed 1 and 1000 mm beyond the exit face was calculated. Cesium iodide (CSI) crystals of 1.5 and 3 mm square cross section and 1, 5, and 10 mm depth were modeled. Both models were also used to determine detector signal and optical gain factor as a function of CsI scintillator thickness, from 2 to 10 mm. Results showed a variation in light output with position of dose deposition of a factor of up to approximately 5, for long, thin scintillators (such as 10 X 1.5 x 1.5 mm3). For short, fat scintillators (such as 1 X 3 X 3 mm3) the light output was more uniform with depth. MC and LLG generally agreed to within 5%. Results for a sensor distance of 1 mm showed an increase in light output the closer the light originates to the exit face, while a distance of 1000 mm showed a decrease in light output the closer the light originates to the exit face. For a sensor distance of 1 mm, the ratio of signal for a 10 mm scintillator to that for a 2 mm scintillator was 1.98, whereas for the 1000 mm distance the ratio was 3.00. The ratio of quantum efficiency (QE) between 10 and 2 mm thicknesses was 4.62. We conclude that these models may be used for detector optimization, with the light guide model suitable for parametric study..

PURPOSE: To investigate the feasibility of fully automated detection of fiducial markers implanted into the prostate using portal images acquired with an electronic portal imaging device. METHODS AND MATERIALS: We have made a direct comparison of 4 different methods (2 template matching-based methods, a method incorporating attenuation and constellation analyses and a cross correlation method) that have been published in the literature for the automatic detection of fiducial markers. The cross-correlation technique requires a-priory information from the portal images, therefore the technique is not fully automated for the first treatment fraction. Images of 7 patients implanted with gold fiducial markers (8 mm in length and 1 mm in diameter) were acquired before treatment (set-up images) and during treatment (movie images) using 1MU and 15MU per image respectively. Images included: 75 anterior (AP) and 69 lateral (LAT) set-up images and 51 AP and 83 LAT movie images. Using the different methods described in the literature, marker positions were automatically identified. RESULTS: The method based upon cross correlation techniques gave the highest percentage detection success rate of 99% (AP) and 83% (LAT) set-up (1MU) images. The methods gave detection success rates of less than 91% (AP) and 42% (LAT) set-up images. The amount of a-priory information used and how it affects the way the techniques are implemented, is discussed. CONCLUSIONS: Fully automated marker detection in set-up images for the first treatment fraction is unachievable using these methods and that using cross-correlation is the best technique for automatic detection on subsequent radiotherapy treatment fractions..

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This study aimed to investigate the effect of body habitus on supraclavicular (SC) dose-volume histogram (DVH) parameters among breast cancer patients according to 3 different techniques. Three SC irradiation plans were generated for 24 postoperative breast cancer patients: (1) direct antero-posterior field only (1fieldP), with dose prescribed to a 3-cm depth; (2) 3-cm depth plan (3cmP) using an antero-posterior field plus a posterior boost with the dose prescription defined to 3 cm; and (3) optimized plan (OptP) similar to 3cmP, with dose prescribed depending on the anatomy. The OptP plans had the least variation in DVH parameters with body habitus; 3cmP plans were the most varied. Conformity index among normal weight patients were 0.73, 0.78, and 0.87 (p = 0.02) and 0.61, 0.6, and 0.82 among overweight-obese patients for 1fieldP, 3cmP, and OptP, respectively (p < 0.001). V95% of the planning target volume among normal weight patients were 72.63%, 78.03%, and 87.18% for 1fieldP, 3cmP, and OptP, respectively (p = 0.02). The corresponding values among overweight-obese patients were 60.5%, 59.62%, and 81.62%, respectively (p = 0.001). Fixed depth dose prescriptions caused greater SC under dose than plans optimized according to patient's anatomy..