Total bilirubin assay differences may cause inconsistent treatment decisions in neonatal hyperbilirubinaemia.

OBJECTIVES: To assess interlaboratory variability of total serum bilirubin (TSB) results in newborns. Initiated following a clinical incident in which a neonate was transferred to a tertiary hospital for treatment of severe hyperbilirubinemia but on arrival was reclassified into a lower risk category due to a 20% difference in TSB between laboratories. METHODS: Fresh residual plasma samples from hospital-born infants were pooled to obtain 11 samples across a range of total bilirubin concentrations. Aliquots were light-protected and measured on 7 commercial platforms at 4 accredited medical laboratories. Data from The Royal College of Pathologists of Australasia Quality Assurance Programs' (RCPAQAP) Neonatal Bilirubin program was analysed. RESULTS: Twenty-four to 30% difference in results for individual samples, largely due to calibration differences between assays. When interpreted according to guidelines, results from different platforms would have led to different clinical interventions in some cases. RCPAQAP results showed significant within-method bias but were not shown to be commutable with patient samples. CONCLUSIONS: There are clinically significant method-dependent differences in TSB results from neonatal samples, consistent with our clinical incident. The differences are largely due to lack of standardisation of calibrator values. This has implications for healthcare resource use and possibly for the neurodevelopment of infants. Intervention is needed at a number of levels, including clinical reporting of incidents arising from discordant results, commitment by manufacturers to ensure metrological traceability of methods with sufficiently low uncertainty in the final measurements, and availability of commutable quality assurance material to monitor assay performance, especially at the clinical decision points for neonatal jaundice.

Technical Note: Deep Learning approach for automatic detection and identification of patient positioning devices for radiation therapy.

PURPOSE: Automatic detection and identification of setup devices, using a deep convolutional neural network (CNN) for real-time multiclass object detection, has the potential to reduce errors in the treatment delivery process by avoiding documentation errors. METHODS: A database of the setup device photos from the most recent 1200 patients treated at our institution was downloaded from the record and verify (R&V) system along with the corresponding setup notes. Images were manually labeled with bounding boxes of each device. A real-time object detection CNN using the "you only look once" (YOLOv2) architecture was trained using transfer learning of a pretrained CNN (ResNet50). The CNN was trained to detect and identify 11 of the most common treatment accessories used at our institution. RESULTS: Using transfer learning of a CNN for multiclass object detection, we are able to automatically detect and identify setup devices in photographs with an accuracy of 96%. CONCLUSIONS: Automation in radiation oncology has the potential to reduce risk. Automatic detection of setup devices is possible using a CNN and transfer learning. This work shows both the value of incident learning systems (ILS) in practice knowledge dissemination, and shows how automation of clinical processes and less reliance on manual documentation has the potential for risk reduction in radiation oncology treatments.

Focal segmental glomerulosclerosis and mild intellectual disability in a patient with a novel de novo truncating TRIM8 mutation.

Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.

Integration of automation into an existing clinical workflow to improve efficiency and reduce errors in the manual treatment planning process for total body irradiation (TBI).

PURPOSE: To identify causes of error, and present the concept of an automated technique that improves efficiency and helps to reduce transcription and manual data entry errors in the treatment planning of total body irradiation (TBI). METHODS: Analysis of incidents submitted to incident learning system (ILS) was performed to identify potential avenues for improvement by implementation of automation of the manual treatment planning process for total body irradiation (TBI). Following this analysis, it became obvious that while the individual components of the TBI treatment planning process were well implemented, the manual 'bridging' of the components (transcribing data, manual data entry etc.) were leading to high potential for error. A C#-based plug-in treatment planning script was developed to remove the manual parts of the treatment planning workflow that were contributing to increased risk. RESULTS: Here we present an example of the implementation of "Glue" programming, combining treatment planning C# scripts with existing spreadsheet calculation worksheets. Prior to the implementation of automation, 35 incident reports related to the TBI treatment process were submitted to the ILS over a 6-year period, with an average of 1.4 ± 1.7 reports submitted per quarter. While no incidents reached patients, reports ranged from minor documentation issues to potential for mistreatment if not caught before delivery. Since the implementation of automated treatment planning and documentation, treatment planning time per patient, including documentation, has been reduced; from an average of 45 min pre-automation to <20 min post-automation. CONCLUSIONS: Manual treatment planning techniques may be well validated, but they are time-intensive and have potential for error. Often the barrier to automating these techniques becomes the time required to "re-code" existing solutions in unfamiliar computer languages. We present the workflow here as a proof of concept that automation may help to improve clinical efficiency and safety for special procedures.

The Current State of Physics Plan Review Training in Medical Physics Residency Programs in North America.

PURPOSE: This study aimed to identify the current state of residency training in physics plan reviews. METHODS AND MATERIALS: A voluntary, anonymous survey was sent to all program directors of accredited therapeutic medical physics residency programs in North America. Survey questions were developed to determine whether and how residents are trained in physics plan reviews. Survey questions were developed using expert validation and cognitive pretesting. RESULTS: Using a prospectively approved study (COMIRB 18-1073), responses were collected from 70 program directors, representing a 70% response rate. All respondents (100%) designated patient safety to be the purpose of physics plan reviews. Of the respondents, 94% indicated that physicists should first receive training in physics plan reviews while in a residency program. The vast majority of respondents (99%) provide training to residents in physics plan reviews. Although 57 programs (81% of respondents) have residents perform physics plan reviews as part of clinical practice (with varying levels of independence), 13 programs (19% of respondents) do not. The majority of respondents use the following training methods: observe staff physicists (96%), perform supervised reviews on actual patients for training or clinical practice (93%), use a checklist (80%), and read reference materials (62%). Although simulation plans with embedded errors would be implemented by 71% of respondents, they are currently used in only 19% of programs. CONCLUSIONS: The present study is the first to characterize chart-check teaching practices in medical physics residency programs. The vast majority of programs currently train residents in physics plan reviews. The most common teaching methods are observing and performing physics plan reviews, but there is variability in the level of resident involvement in clinical practice for physics plan reviews. There is room for the field to consider advancing current training methods, which is especially important given the critical roles that physics plan reviews have with regard to patient safety.

Simulation of x-ray-induced acoustic imaging for absolute dosimetry: Accuracy of image reconstruction methods.

PURPOSE: Three-dimensional in-vivo dose verification is one of the standing challenges in radiation therapy. X-ray-induced acoustic tomography has recently been proposed as an imaging method for use in in-vivo dosimetry. The aim of this study was to investigate the accuracy of reconstructing three-dimensional (3D) absolute dose using x-ray-induced acoustic tomography. We performed this investigation using two different tomographic dose reconstruction techniques. METHODS: Two examples of 3D dose reconstruction techniques for x-ray acoustic imaging are investigated. Dose distributions are calculated for varying field sizes using a clinical treatment planning system. The induced acoustic pressure waves which are generated by the increase in temperature due to the absorption of pulsed MV x-rays are simulated using an advanced numerical modeling package for acoustic wave propagation in the time domain. Two imaging techniques, back projection and iterative time reversal, are used to reconstruct the 3D dose distribution in a water phantom with open fields. Image analysis is performed and reconstructed depth dose curves from x-ray acoustic imaging are compared to the depth dose curves calculated from the treatment planning system. Calculated field sizes from the reconstructed dose profiles by back projection and time reversal are compared to the planned field size to determine their accuracy. The iterative time reversal imaging technique is also used to reconstruct dose in an example clinical dose distribution. Image analysis of this clinical test case is performed using the gamma passing rate. In addition, gamma passing rates are used to validate the stopping criteria in the iterative time reversal method. RESULTS: Water phantom simulations showed that back projection does not adequately reconstruct the shape and intensity of the depth dose. When compared to the depth of maximum dose calculated by a treatment planning system, the maximum dose depth by back projection is shifted deeper by 55 and 75 mm for 4 × 4 cm and 10 × 10 cm field sizes, respectively. The reconstructed depth dose by iterative time reversal accurately agrees with the planned depth dose for a 4 × 4 cm field size and is shifted deeper by 12 mm for the 10 × 10 cm field size. When reconstructing field sizes, the back projection method leads to 18% and 35% larger sizes for the 4 × 4 cm and 10 × 10 cm fields, respectively, whereas the iterative time reversal method reconstructs both field sizes with < 2% error. For the clinical dose distribution, we were able to reconstruct the dose delivered by a 1 degree sub-arc with a good accuracy. The reconstructed and planned doses were compared using gamma analysis, with> 96% gamma passing rate at 3%/2 mm. CONCLUSIONS: Our results show that the 3D x-ray acoustic reconstructed dose by iterative time reversal is considerably more accurate than the dose reconstructed by back projection. Iterative time reversal imaging has a potential for use in 3D absolute dosimetry.

Safety-oriented design of in-house software for new techniques: A case study using a model-based 4DCT protocol.

PURPOSE: In-house software is commonly employed to implement new imaging and therapy techniques before commercial solutions are available. Risk analysis methods, as detailed in the TG-100 report of the American Association of Physicists in Medicine, provide a framework for quality management of processes but offer little guidance on software design. In this work, we examine a novel model-based four-dimensional computed tomography (4DCT) protocol using the TG-100 approach and describe two additional methods for promoting safety of the associated in-house software. METHODS: To implement a previously published model-based 4DCT protocol, in-house software was necessary for tasks such as synchronizing a respiratory signal to computed tomography images, deformable image registration (DIR), model parameter fitting, and interfacing with a treatment planning system. A process map was generated detailing the workflow. Failure modes and effects analysis (FMEA) was performed to identify critical steps and guide quality interventions. Software system safety was addressed through writing "use cases," narratives that characterize the behavior of the software, for all major operations to elicit safety requirements. Safety requirements were codified using the easy approach to requirements syntax (EARS) to ensure testability and eliminate ambiguity. RESULTS: Sixty-one failure modes were identified and assigned risk priority numbers using FMEA. Resultant quality management interventions include integration of a comprehensive reporting and logging system into the software, mandating daily and monthly equipment quality assurance procedures, and a checklist to be completed at image acquisition. Use cases and resulting safety requirements informed the design of needed in-house software as well as a suite of tests performed during the image generation process. CONCLUSIONS: TG-100 methods were used to construct a process-level quality management program for a 4DCT imaging protocol. Two supplemental tools from the field of requirements engineering facilitated elicitation and codification of safety requirements that informed the design and testing of in-house software necessary to implement the protocol. These general tools can be applied to promote safety when in-house software is needed to bring new techniques to the clinic.

Model-Interpolated Gating for Magnetic Resonance Image-Guided Radiation Therapy.

PURPOSE: To develop and validate a technique for radiation therapy gating using slow (≤1 frame per second) magnetic resonance imaging (MRI) and a motion model. Proposed uses of the technique include radiation therapy gating using T2-weighted images and conducting additional imaging studies during gated treatments. METHODS AND MATERIALS: The technique uses a physiologically guided breathing motion model to interpolate deformed target position between 2-dimensional (2D) MRI images acquired every 1 to 3 seconds. The model is parameterized by a 1-dimensional respiratory bellows surrogate and is continuously updated with the most recently acquired 2D images. A phantom and 8 volunteers were imaged with a 0.35T MRI-guided radiation therapy system. A balanced steady-state free precession sequence with a 2D frame rate of 3 frames per second was used to evaluate the technique. The accuracy and beam-on positive predictive value (PPV) of the model-based gating decisions were evaluated using the gating decisions derived from imaging as a ground truth. A T2-weighted gating offline proof-of-concept study using a half-Fourier, single-shot, turbo-spin echo sequence is reported. RESULTS: Model-interpolated gating accuracy, beam-on PPV, and median absolute distances between model and image-tracked target centroids were, on average, 98.3%, 98.4%, and 0.33 mm, respectively, in the balanced steady-state free precession phantom studies and 93.7%, 92.1%, and 0.86 mm, respectively, in the volunteer studies. T2 model-interpolated gating in 6 volunteers yielded an average accuracy and PPV of 94.3% and 92.5%, respectively, and the mean absolute median distance between modeled and imaged target centroids was 0.86 mm. CONCLUSIONS: This work demonstrates the concept of model-interpolated gating for MRI-guided radiation therapy. The technique was found to be potentially sufficiently accurate for clinical use. Further development is needed to accommodate out-of-plane motion and the use of an internal MR-based respiratory surrogate.

Comparison of lung tumor motion measured using a model-based 4DCT technique and a commercial protocol.

PURPOSE: To compare lung tumor motion measured with a model-based technique to commercial 4-dimensional computed tomography (4DCT) scans and describe a workflow for using model-based 4DCT as a clinical simulation protocol. METHODS AND MATERIALS: Twenty patients were imaged using a model-based technique and commercial 4DCT. Tumor motion was measured on each commercial 4DCT dataset and was calculated on model-based datasets for 3 breathing amplitude percentile intervals: 5th to 85th, 5th to 95th, and 0th to 100th. Internal target volumes (ITVs) were defined on the 4DCT and 5th to 85th interval datasets and compared using Dice similarity. Images were evaluated for noise and rated by 2 radiation oncologists for artifacts. RESULTS: Mean differences in tumor motion magnitude between commercial and model-based images were 0.47 ± 3.0, 1.63 ± 3.17, and 5.16 ± 4.90 mm for the 5th to 85th, 5th to 95th, and 0th to 100th amplitude intervals, respectively. Dice coefficients between ITVs defined on commercial and 5th to 85th model-based images had a mean value of 0.77 ± 0.09. Single standard deviation image noise was 11.6 ± 9.6 HU in the liver and 6.8 ± 4.7 HU in the aorta for the model-based images compared with 57.7 ± 30 and 33.7 ± 15.4 for commercial 4DCT. Mean model error within the ITV regions was 1.71 ± 0.81 mm. Model-based images exhibited reduced presence of artifacts at the tumor compared with commercial images. CONCLUSION: Tumor motion measured with the model-based technique using the 5th to 85th percentile breathing amplitude interval corresponded more closely to commercial 4DCT than the 5th to 95th or 0th to 100th intervals, which showed greater motion on average. The model-based technique tended to display increased tumor motion when breathing amplitude intervals wider than 5th to 85th were used because of the influence of unusually deep inhalations. These results suggest that care must be taken in selecting the appropriate interval during image generation when using model-based 4DCT methods.

Dependence of subject-specific parameters for a fast helical CT respiratory motion model on breathing rate: an animal study.

To determine if the parameters relating lung tissue displacement to a breathing surrogate signal in a previously published respiratory motion model vary with the rate of breathing during image acquisition. An anesthetized pig was imaged using multiple fast helical scans to sample the breathing cycle with simultaneous surrogate monitoring. Three datasets were collected while the animal was mechanically ventilated with different respiratory rates: 12 bpm (breaths per minute), 17 bpm, and 24 bpm. Three sets of motion model parameters describing the correspondences between surrogate signals and tissue displacements were determined. The model error was calculated individually for each dataset, as well asfor pairs of parameters and surrogate signals from different experiments. The values of one model parameter, a vector field denoted [Formula: see text] which related tissue displacement to surrogate amplitude, determined for each experiment were compared. The mean model error of the three datasets was 1.00 ± 0.36 mm with a 95th percentile value of 1.69 mm. The mean error computed from all combinations of parameters and surrogate signals from different datasets was 1.14 ± 0.42 mm with a 95th percentile of 1.95 mm. The mean difference in [Formula: see text] over all pairs of experiments was 4.7% ± 5.4%, and the 95th percentile was 16.8%. The mean angle between pairs of [Formula: see text] was 5.0 ± 4.0 degrees, with a 95th percentile of 13.2 mm. The motion model parameters were largely unaffected by changes in the breathing rate during image acquisition. The mean error associated with mismatched sets of parameters and surrogate signals was 0.14 mm greater than the error achieved when using parameters and surrogate signals acquired with the same breathing rate, while maximum respiratory motion was 23.23 mm on average.

Initial clinical observations of intra- and interfractional motion variation in MR-guided lung SBRT.

OBJECTIVE: To evaluate variations in intra- and interfractional tumour motion, and the effect on internal target volume (ITV) contour accuracy, using deformable image registration of real-time two-dimensional-sagittal cine-mode MRI acquired during lung stereotactic body radiation therapy (SBRT) treatments. METHODS: Five lung tumour patients underwent free-breathing SBRT treatments on the ViewRay system, with dose prescribed to a planning target volume (defined as a 3-6 mm expansion of the 4DCT-ITV). Sagittal slice cine-MR images (3.5 × 3.5 mm2 pixels) were acquired through the centre of the tumour at 4 frames per second throughout the treatments (3-4 fractions of 21-32 min). Tumour gross tumour volumes (GTVs) were contoured on the first frame of the MR cine and tracked for the first 20 min of each treatment using offline optical-flow based deformable registration implemented on a GPU cluster. A ground truth ITV (MR-ITV20 min) was formed by taking the union of tracked GTV contours. Pseudo-ITVs were generated from unions of the GTV contours tracked over 10 s segments of image data (MR-ITV10 s). RESULTS: Differences were observed in the magnitude of median tumour displacement between days of treatments. MR-ITV10 s areas were as small as 46% of the MR-ITV20 min. CONCLUSION: An ITV offers a "snapshot" of breathing motion for the brief period of time the tumour is imaged on a specific day. Real-time MRI over prolonged periods of time and over multiple treatment fractions shows that ITV size varies. Further work is required to investigate the dosimetric effect of these results. Advances in knowledge: Five lung tumour patients underwent free-breathing MRI-guided SBRT treatments, and their tumours tracked using deformable registration of cine-mode MRI. The results indicate that variability of both intra- and interfractional breathing amplitude should be taken into account during planning of lung radiotherapy.

Investigating the minimum scan parameters required to generate free-breathing motion artefact-free fast-helical CT.

OBJECTIVE: A recently proposed "5DCT" protocol uses deformable registration of free-breathing fast-helical CT scans to generate a breathing motion model. In order to allow accurate registration, free-breathing images are required to be free of doubling-artefacts, which arise when tissue motion is greater than scan speed. METHODS: Using a unique set of digital phantoms based on patient data and verified with a motion phantom, this work identifies the minimum scanner parameters required to successfully generate free-breathing artefact-free fast-helical scans. A motion phantom and 5 patients were imaged 25 times under free-breathing conditions in alternating directions with a 64-slice CT scanner employing a low-dose fast-helical protocol. A series of high temporal resolution (0.1 s) 5DCT scan data sets was generated in each case. A simulated CT scanner was used to "image" each free-breathing data set. Various CT scanner detector widths and rotation times were simulated, and verified using the motion phantom results. Motion-induced artefacts were quantified in patient images using structural similarity maps to determine the similarity between axial slices. RESULTS: Increasing amounts of motion-induced artefacts were observed with increasing rotation times >0.2 s for 16 mm detector configuration. CONCLUSION: The current generation of 16-slice CT scanners, which are present in the majority of Radiation Oncology departments, are not capable of generating free-breathing sorting artefact-free images required for 5DCT. Advances in knowledge: A recently proposed "5DCT" protocol uses deformable registration of free-breathing fast-helical CT scans to generate a breathing motion model. In order to allow accurate registration, free-breathing images are required to be free of doubling-artefacts, which arise when tissue motion is greater than scan speed. The results suggest that the current generation of 16-slice CT scanners, present in the majority of Radiation Oncology departments, are not capable of generating the free-breathing images required for 5DCT.

Online Adaptive Radiation Therapy: Implementation of a New Process of Care.

Onboard magnetic resonance imaging (MRI) guided radiotherapy is now clinically available in nine centers in the world. This technology has facilitated the clinical implementation of online adaptive radiotherapy (OART), or the ability to alter the daily treatment plan based on tumor and anatomical changes in real-time while the patient is on the treatment table. However, due to the time sensitive nature of OART, implementation in a large and busy clinic has many potential obstacles as well as patient-related safety considerations. In this work, we have described the implementation of this new process of care in the Department of Radiation Oncology at the University of California, Los Angeles (UCLA). We describe the rationale, the initial challenges such as treatment time considerations, technical issues during the process of re-contouring, re-optimization, quality assurance, as well as our current solutions to overcome these challenges. In addition, we describe the implementation of a coverage system with a physician of the day as well as online planners (physicists or dosimetrists) to oversee each OART treatment with patient-specific 'hand-off' directives from the patient's treating physician. The purpose of this effort is to streamline the process without compromising treatment quality and patient safety. As more MRI-guided radiotherapy programs come online, we hope that our experience can facilitate successful adoption of OART in a way that maximally benefits the patient.

Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.

PURPOSE: Magnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV. METHODS: The motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique. RESULTS: Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm. CONCLUSIONS: Our results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study.

Technical Note: Analysis of motion blurring artifact in fast helical free-breathing thoracic CT scans.

PURPOSE: The aim of this study was to measure and characterize breathing-induced motion artifacts in fast helical free-breathing CT scans. METHODS: Ten lung cancer patients were scanned using fast helical CT during free breathing. In each case, 25 low-dose CT scans were acquired in alternating craniocaudal and caudocranial directions. A bellow-based breathing surrogate was simultaneously acquired. A published breathing motion model was used to estimate the diaphragm craniodaudal velocity at each CT scan. The Hounsfield unit (HU) profiles passing through a small square (7 × 7 mm2 ) portion of the diaphragm were examined and fit to error functions, which were used to characterize the motion blur. The HU profiles that intersected diaphragm-adjacent non-parenchymal tissue were excluded from analysis. The five profiles for each scan that were best isolated from non-parenchymal tissue were used to determine the amount of blurring. A convolution-based blurring model was also employed to compare against the human data. RESULTS: There was a distinct relationship between blurring and diaphragm speed. The convolution model well described the blurring behavior in the patients. Most of the CT scans were acquired at tissue velocities less than 20 mm s-1 , which was the threshold where blurring exceeded 1 mm (corresponding to the slice spacing in this study). CONCLUSIONS: Breathing motion-induced blurring occurs even for relatively fast modern helical CT scans. Measurable motion-induced blurring occurs for velocities greater than 15 mm s-1 and greater than 1 mm for velocities greater than 20 mm s-1 . Methods to manage the residual blurring artifacts will need to be developed to maximize the image quality for free-breathing CT protocols.

Technical Note: Dosimetric effects of couch position variability on treatment plan quality with an MRI-guided Co-60 radiation therapy machine.

PURPOSE: Magnetic resonance imaging (MRI) guidance in radiation therapy brings real-time imaging and adaptive planning into the treatment vault where it can account for interfraction and intrafraction movement of soft tissue. The only commercially available MRI-guided radiation therapy device is a three-head (60)Co and MRI system with an integrated treatment planning system (TPS). Couch attenuation of the beam of up to 20% is well modeled in the TPS. Variations in the patient's day-to-day position introduce discrepancies in the actual couch attenuation as modeled in the treatment plan. For this reason, the authors' institution avoids plans with beams that pass through or near the couch edges. This study investigates the effects of differential beam attenuation by the couch due to couch shifts in order to determine whether couch edge avoidance restrictions can be lifted. Couch shifts were simulated using a Monte Carlo treatment planning system and ion chamber measurements performed for validation. METHODS: A total of 27 plans from 23 patients were investigated. Couch shifts of 1 and 2 cm were introduced in combinations of lateral and vertical directions to simulate patient position variations giving 16 shifted plans per reference plan. The 1 and 2 cm shifts were based on shifts recorded in 320 treatment fractions. RESULTS: Following TG176 recommendations for measurement methods, couch attenuation measurements agreed with TPS modeled attenuation to within 2.1%. Planning target volume D95 changed less than 1% for 1 and 2 cm couch shifts in only the x-direction and less than 3% for all directions. CONCLUSIONS: Dosimetry of all plans tested was robust to couch shifts up to ±2 cm. In general, couch shifts resulted in clinically insignificant dosimetric deviations. It is conceivable that in certain cases with large systematic couch shifts and plans that are particularly sensitive to shifts, dosimetric changes might rise to a clinically significant level.

A Method for Assessing Ground-Truth Accuracy of the 5DCT Technique.

PURPOSE: To develop a technique that assesses the accuracy of the breathing phase-specific volume image generation process by patient-specific breathing motion model using the original free-breathing computed tomographic (CT) scans as ground truths. METHODS: Sixteen lung cancer patients underwent a previously published protocol in which 25 free-breathing fast helical CT scans were acquired with a simultaneous breathing surrogate. A patient-specific motion model was constructed based on the tissue displacements determined by a state-of-the-art deformable image registration. The first image was arbitrarily selected as the reference image. The motion model was used, along with the free-breathing phase information of the original 25 image datasets, to generate a set of deformation vector fields that mapped the reference image to the 24 nonreference images. The high-pitch helically acquired original scans served as ground truths because they captured the instantaneous tissue positions during free breathing. Image similarity between the simulated and the original scans was assessed using deformable registration that evaluated the pointwise discordance throughout the lungs. RESULTS: Qualitative comparisons using image overlays showed excellent agreement between the simulated images and the original images. Even large 2-cm diaphragm displacements were very well modeled, as was sliding motion across the lung-chest wall boundary. The mean error across the patient cohort was 1.15 ± 0.37 mm, and the mean 95th percentile error was 2.47 ± 0.78 mm. CONCLUSION: The proposed ground truth-based technique provided voxel-by-voxel accuracy analysis that could identify organ-specific or tumor-specific motion modeling errors for treatment planning. Despite a large variety of breathing patterns and lung deformations during the free-breathing scanning session, the 5-dimensionl CT technique was able to accurately reproduce the original helical CT scans, suggesting its applicability to a wide range of patients.

Technical Note: Simulation of 4DCT tumor motion measurement errors.

PURPOSE: To determine if and by how much the commercial 4DCT protocols under- and overestimate tumor breathing motion. METHODS: 1D simulations were conducted that modeled a 16-slice CT scanner and tumors moving proportionally to breathing amplitude. External breathing surrogate traces of at least 5-min duration for 50 patients were used. Breathing trace amplitudes were converted to motion by relating the nominal tumor motion to the 90th percentile breathing amplitude, reflecting motion defined by the more recent 5DCT approach. Based on clinical low-pitch helical CT acquisition, the CT detector moved according to its velocity while the tumor moved according to the breathing trace. When the CT scanner overlapped the tumor, the overlapping slices were identified as having imaged the tumor. This process was repeated starting at successive 0.1 s time bin in the breathing trace until there was insufficient breathing trace to complete the simulation. The tumor size was subtracted from the distance between the most superior and inferior tumor positions to determine the measured tumor motion for that specific simulation. The effect of the scanning parameter variation was evaluated using two commercial 4DCT protocols with different pitch values. Because clinical 4DCT scan sessions would yield a single tumor motion displacement measurement for each patient, errors in the tumor motion measurement were considered systematic. The mean of largest 5% and smallest 5% of the measured motions was selected to identify over- and underdetermined motion amplitudes, respectively. The process was repeated for tumor motions of 1-4 cm in 1 cm increments and for tumor sizes of 1-4 cm in 1 cm increments. RESULTS: In the examined patient cohort, simulation using pitch of 0.06 showed that 30% of the patients exhibited a 5% chance of mean breathing amplitude overestimations of 47%, while 30% showed a 5% chance of mean breathing amplitude underestimations of 36%; with a separate simulation using pitch of 0.1 showing, respectively, 37% overestimation and 61% underestimation. CONCLUSIONS: The simulation indicates that commercial low-pitch helical 4DCT processes potentially yield large tumor motion measurement errors, both over- and underestimating the tumor motion.

Comparison of breathing gated CT images generated using a 5DCT technique and a commercial clinical protocol in a porcine model.

PURPOSE: To demonstrate that a "5DCT" technique which utilizes fast helical acquisition yields the same respiratory-gated images as a commercial technique for regular, mechanically produced breathing cycles. METHODS: Respiratory-gated images of an anesthetized, mechanically ventilated pig were generated using a Siemens low-pitch helical protocol and 5DCT for a range of breathing rates and amplitudes and with standard and low dose imaging protocols. 5DCT reconstructions were independently evaluated by measuring the distances between tissue positions predicted by a 5D motion model and those measured using deformable registration, as well by reconstructing the originally acquired scans. Discrepancies between the 5DCT and commercial reconstructions were measured using landmark correspondences. RESULTS: The mean distance between model predicted tissue positions and deformably registered tissue positions over the nine datasets was 0.65 ± 0.28 mm. Reconstructions of the original scans were on average accurate to 0.78 ± 0.57 mm. Mean landmark displacement between the commercial and 5DCT images was 1.76 ± 1.25 mm while the maximum lung tissue motion over the breathing cycle had a mean value of 27.2 ± 4.6 mm. An image composed of the average of 30 deformably registered images acquired with a low dose protocol had 6 HU image noise (single standard deviation) in the heart versus 31 HU for the commercial images. CONCLUSIONS: An end to end evaluation of the 5DCT technique was conducted through landmark based comparison to breathing gated images acquired with a commercial protocol under highly regular ventilation. The techniques were found to agree to within 2 mm for most respiratory phases and most points in the lung.

The polydisperse acoustic signature of rigid microbubbles.

Microbubbles are used in medical ultrasound imaging as contrast agents to image the vascular bed under the mode of Ultrasound Contrast Imaging (UCI). The microbubble shell determines the acoustic response and hence the signal that is utilized to form the images in UCI. Single microbubble signals from BiSphere™ (POINT Biomedical, San Carlos, CA, USA) microbubbles were captured using a clinical ultrasound system. Three main typical responses of microbubbles were identified, a) full duration echo, b) echo with duration shorter than the incident pulse and c) echo that in part resembles that in (b) and in addition prior to that another short duration initial lower amplitude signal. These data corroborate that the shell structural and nanomechanical property provide the different responses at different microbubble sizes. These different signals present an opportunity for tracking the movement of well differentiated single microbubbles particularly with novel super-resolution imaging methods that require sparse microbubble populations.