An IMRT planning technique for treating whole breast or chest wall with regional lymph nodes on Halcyon and Ethos.

PURPOSE/OBJECTIVE: Field size limitations on Halcyon and Ethos treatment machines largely preclude use of the conventional monoisocentric three-field technique for breast/chest wall and regional lymph nodes. We present an alternative, IMRT-based planning approach that facilitates treatment on Halcyon and Ethos while preserving plan quality. MATERIALS/METHODS: Eight breast and regional node cases (four left-sided, four right-sided) were planned for an Ethos machine using a 15-17 field IMRT technique. Institutional plan quality metrics for CTV and PTV coverage and OAR sparing were assessed. Five plans (four right-sided, one left-sided) were also planned using a hybrid 3D multisocenter technique. CTV coverage and OAR sparing were compared to the IMRT plans. Eclipse scripting tools were developed to aid in beam placement and plan evaluation through a set of dosimetric scorecards, and both are shared publicly. RESULTS: On average, the IMRT plans achieved breast CTV and PTV coverage at 50 Gy of 97.9% and 95.7%, respectively. Supraclavicular CTV and PTV coverages at 45 Gy were 100% and 95.5%. Axillary lymph node CTV and PTV coverages at 45 Gy were 100% and 97.1%, and IMN CTV coverage at 45 Gy was 99.2%. Mean ipsilateral lung V20 Gy was 19.3%, and average mean heart dose was 1.6 Gy for right-sided cases and 3.0 Gy for left-sided. In comparison to the hybrid 3D plans, IMRT plans achieved higher breast and supraclavicular CTV coverage (99.9% vs. 98.6% and 99.9% vs. 93.4%), higher IMN coverage (99.6% vs. 78.2%), and lower ipsilateral lung V20 Gy (19.6% vs. 28.2%). CONCLUSION: Institutional plan quality benchmarks were achieved for all eight cases using the IMRT-based planning approach. The IMRT-based planning approach offered superior conformity and OAR sparing than a competing hybrid 3D approach.

Dosimetric evaluation of respiratory gating on a 0.35-T magnetic resonance-guided radiotherapy linac.

PURPOSE: The commercial 0.35-T magnetic resonance imaging (MRI)-guided radiotherapy vendor ViewRay recently introduced upgraded real-time imaging frame rates based on compressed sensing techniques. Furthermore, additional motion tracking algorithms were made available. Compressed sensing allows for increased image frame rates but may compromise image quality. To assess the impact of this upgrade on respiratory gating accuracy, we evaluated gated dose distributions pre- and post-upgrade using a motion phantom and radiochromic film. METHODS: Seven motion waveforms (four artificial, two patient-derived free-breathing, and one breath-holding) were used to drive an MRI-compatible motion phantom. A treatment plan was developed to deliver a 3-cm diameter spherical dose distribution typical of a stereotactic body radiotherapy plan. Gating was performed using 4-frames per second (fps) imaging pre-upgrade on the "default" tracking algorithm and 8-fps post-upgrade using the "small mobile targets" (SMT) and "large deforming targets" (LDT) tracking algorithms. Radiochromic film was placed in a moving insert within the phantom to measure dose. The planned and delivered dose distributions were compared using the gamma index with 3%/3-mm criteria. Dose-area histograms were produced to calculate the dose to 95% (D95) of the sphere planning target volume (PTV) and two simulated gross tumor volumes formed by contracting the PTV by 3 and 5 mm, respectively. RESULTS: Gamma pass rates ranged from 18% to 93% over the 21 combinations of breathing trace and gating conditions examined. D95 ranged from 206 to 514 cGy. On average, the LDT algorithm yielded lower gamma and D95 values than the default and SMT algorithms. CONCLUSION: Respiratory gating at 8 fps with the new tracking algorithms provides similar gating performance to the original algorithm with 4 fps, although the LDT algorithm had lower accuracy for our non-deformable target. This indicates that the choice of deformable image registration algorithm should be chosen deliberately based on whether the target is rigid or deforming.

Photon-counting, energy-resolving and super-resolution phase contrast X-ray imaging using an integrating detector.

This work demonstrates the use of a scientific-CMOS (sCMOS) energy-integrating detector as a photon-counting detector, thereby eliminating dark current and read-out noise issues, that simultaneously provides both energy resolution and sub-pixel spatial resolution for X-ray imaging. These capabilities are obtained by analyzing visible light photon clouds that result when X-ray photons produce fluorescence from a scintillator in front of the visible light sensor. Using low-fluence monochromatic X-ray projections to avoid overlapping photon clouds, the centroid of individual X-ray photon interactions was identified. This enabled a tripling of the spatial resolution of the detector to 6.71 ± 0.04 µm. By calculating the total charge deposited by this interaction, an energy resolution of 61.2 ± 0.1% at 17 keV was obtained. When combined with propagation-based phase contrast imaging and phase retrieval, a signal-to-noise ratio of up to 15 ± 3 was achieved for an X-ray fluence of less than 3 photons/mm2.

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.

Motion compensated cone-beam CT reconstruction using ana priorimotion model from CT simulation: a pilot study.

Objective. To combat the motion artifacts present in traditional 4D-CBCT reconstruction, an iterative technique known as the motion-compensated simultaneous algebraic reconstruction technique (MC-SART) was previously developed. MC-SART employs a 4D-CBCT reconstruction to obtain an initial model, which suffers from a lack of sufficient projections in each bin. The purpose of this study is to demonstrate the feasibility of introducing a motion model acquired during CT simulation to MC-SART, coined model-based CBCT (MB-CBCT).Approach. For each of 5 patients, we acquired 5DCTs during simulation and pre-treatment CBCTs with a simultaneous breathing surrogate. We cross-calibrated the 5DCT and CBCT breathing waveforms by matching the diaphragms and employed the 5DCT motion model parameters for MC-SART. We introduced the Amplitude Reassignment Motion Modeling technique, which measures the ability of the model to control diaphragm sharpness by reassigning projection amplitudes with varying resolution. We evaluated the sharpness of tumors and compared them between MB-CBCT and 4D-CBCT. We quantified sharpness by fitting an error function across anatomical boundaries. Furthermore, we compared our MB-CBCT approach to the traditional MC-SART approach. We evaluated MB-CBCT's robustness over time by reconstructing multiple fractions for each patient and measuring consistency in tumor centroid locations between 4D-CBCT and MB-CBCT.Main results. We found that the diaphragm sharpness rose consistently with increasing amplitude resolution for 4/5 patients. We observed consistently high image quality across multiple fractions, and observed stable tumor centroids with an average 0.74 ± 0.31 mm difference between the 4D-CBCT and MB-CBCT. Overall, vast improvements over 3D-CBCT and 4D-CBCT were demonstrated by our MB-CBCT technique in terms of both diaphragm sharpness and overall image quality.Significance. This work is an important extension of the MC-SART technique. We demonstrated the ability ofa priori5DCT models to provide motion compensation for CBCT reconstruction. We showed improvements in image quality over both 4D-CBCT and the traditional MC-SART approach.

An analysis of the regional heterogeneity in tissue elasticity in lung cancer patients with COPD.

Purpose: Recent advancements in obtaining image-based biomarkers from CT images have enabled lung function characterization, which could aid in lung interventional planning. However, the regional heterogeneity in these biomarkers has not been well documented, yet it is critical to several procedures for lung cancer and COPD. The purpose of this paper is to analyze the interlobar and intralobar heterogeneity of tissue elasticity and study their relationship with COPD severity. Methods: We retrospectively analyzed a set of 23 lung cancer patients for this study, 14 of whom had COPD. For each patient, we employed a 5DCT scanning protocol to obtain end-exhalation and end-inhalation images and semi-automatically segmented the lobes. We calculated tissue elasticity using a biomechanical property estimation model. To obtain a measure of lobar elasticity, we calculated the mean of the voxel-wise elasticity values within each lobe. To analyze interlobar heterogeneity, we defined an index that represented the properties of the least elastic lobe as compared to the rest of the lobes, termed the Elasticity Heterogeneity Index (EHI). An index of 0 indicated total homogeneity, and higher indices indicated higher heterogeneity. Additionally, we measured intralobar heterogeneity by calculating the coefficient of variation of elasticity within each lobe. Results: The mean EHI was 0.223 ± 0.183. The mean coefficient of variation of the elasticity distributions was 51.1% ± 16.6%. For mild COPD patients, the interlobar heterogeneity was low compared to the other categories. For moderate-to-severe COPD patients, the interlobar and intralobar heterogeneities were highest, showing significant differences from the other groups. Conclusion: We observed a high level of lung tissue heterogeneity to occur between and within the lobes in all COPD severity cases, especially in moderate-to-severe cases. Heterogeneity results demonstrate the value of a regional, function-guided approach like elasticity for procedures such as surgical decision making and treatment planning.

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Quantifying lung aeration in neonatal lambs at birth using lung ultrasound.

Background: Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration. Methods: Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0-50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges. Results: All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r 2 = 0.71). Conclusion: LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.

Technical Note: Investigating internal-external motion correlation using fast helical CT.

PURPOSE: To quantify the use of anterior torso skin surface position measurement as a breathing surrogate. METHODS: Fourteen patients were scanned 25 times in alternating directions using a free-breathing low-mA fast helical CT protocol. Simultaneously, an abdominal pneumatic bellows was used as a real-time breathing surrogate. The imaged diaphragm dome position was used as a gold standard surrogate, characterized by localizing the most superior points of the diaphragm dome in each lung. These positions were correlated against the bellows signal acquired at the corresponding scan times. The bellows system has been shown to have a slow linear drift, and the bellows-to-CT synchronization process had a small uncertainty, so the drift and time offset were determined by maximizing the correlation coefficient between the craniocaudal diaphragm position and the drift-corrected bellows signal. The corresponding fit was used to model the real-time diaphragm position. To estimate the effectiveness of skin surface positions as surrogates, the anterior torso surface position was measured from the CT scans and correlated against the diaphragm position model. The residual error was defined as the root-mean-square correlation residual with the breathing amplitude normalized to the 5th to 95th breathing amplitude percentiles. The fit residual errors were analyzed over the surface for the fourteen studied patients and reported as percentages of the 5th to 95th percentile ranges. RESULTS: A strong correlation was measured between the diaphragm motion and the abdominal bellows signal with an average residual error of 9.21% and standard deviation of 3.77%. In contrast, the correlations between the diaphragm position model and patient surface positions varied throughout the torso and from patient to patient. However, a consistently high correlation was found near the abdomen for each patient, and the average minimum residual error relating the skin surface to the diaphragm was 11.8% with a standard deviation of 4.61%. CONCLUSIONS: The thoracic patient surface was found to be an accurate surrogate, but the accuracy varied across the surface sufficiently that care would need to be taken to use the surface as an accurate and reliable surrogate. Future studies will use surface imaging to determine surface patch algorithms that utilize the entire chest as well as thoracic and abdominal breathing relationships.

Ventilation measurements using fast-helical free-breathing computed tomography.

PURPOSE: To examine the use of multiple fast-helical free breathing computed tomography (FHFBCT) scans for ventilation measurement. METHODS: Ten patients were scanned 25 times in alternating directions using a FHFBCT protocol. Simultaneously, an abdominal pneumatic bellows was used as a real-time breathing surrogate. Regions-of-interest (ROIs) were selected from the upper right lungs of each patient for analysis. The ROIs were first registered using a published registration technique (pTV). A subsequent follow-up registration employed an objective function with two terms, a ventilation-adjusted Hounsfield Unit difference and a conservation-of-mass term labeled ΔΓ that denoted the difference between the deformation Jacobian and the tissue density ratio. The ventilations were calculated voxel-by-voxel as the slope of a first-order fit of the Jacobian as a function of the breathing amplitude. RESULTS: The ventilations of the 10 patients showed different patterns and magnitudes. The average ventilation calculated from the deformation vector fields (DVFs) of the pTV and secondary registration was nearly identical, but the standard deviation of the voxel-to-voxel differences was approximately 0.1. The mean of the 90th percentile values of ΔΓ was reduced from 0.153 to 0.079 between the pTV and secondary registration, implying first that the secondary registration improved the conservation-of-mass criterion by almost 50% and that on average the correspondence between the Jacobian and density ratios as demonstrated by ΔΓ was less than 0.1. This improvement occurred in spite of the average of the 90th percentile changes in the DVF magnitudes being only 0.58 mm. CONCLUSIONS: This work introduces the use of multiple free-breathing CT scans for free-breathing ventilation measurements. The approach has some benefits over the traditional use of 4-dimensional CT (4DCT) or breath-hold scans. The benefit over 4DCT is that FHFBCT does not have sorting artifacts. The benefits over breath-hold scans include the relatively small motion induced by quiet respiration versus deep-inspiration breath hold and the potential for characterizing dynamic breathing processes that disappear during breath hold.

Systematic feasibility analysis of performing elastography using reduced dose CT lung image pairs.

PURPOSE: Elastography using computer tomography (CT) is a promising methodology that can provide patient-specific regional distributions of lung biomechanical properties. The purpose of this paper is to investigate the feasibility of performing elastography using simulated lower dose CT scans. METHODS: A cohort of eight patient CT image pairs were acquired with a tube current-time product of 40 mAs for estimating baseline lung elastography results. Synthetic low mAs CT scans were generated from the baseline scans to simulate the additional noise that would be present in acquisitions at 30, 25, and 20 mAs, respectively. For the simulated low mAs scans, exhalation and inhalation datasets were registered using an in-house optical flow deformable image registration algorithm. The registered deformation vector fields (DVFs) were taken to be ground truth for the elastography process. A model-based elasticity estimation was performed for each of the reduced mAs datasets, in which the goal was to optimize the elasticity distribution that best represented their respective DVFs. The estimated elasticity and the DVF distributions of the reduced mAs scans were then compared with the baseline elasticity results for quantitative accuracy purposes. RESULTS: The DVFs for the low mAs and baseline scans differed from each other by an average of 1.41 mm, which can be attributed to the noise added by the simulated reduction in mAs. However, the elastography results using the DVFs from the reduced mAs scans were similar from the baseline results, with an average elasticity difference of 0.65, 0.71, and 0.76 kPa, respectively. This illustrates that elastography can provide equivalent results using low-dose CT scans. CONCLUSIONS: Elastography can be performed equivalently using CT image pairs acquired with as low as 20 mAs. This expands the potential applications of CT-based elastography.

A quantitative analysis of biomechanical lung model consistency using 5DCT datasets.

PURPOSE: Lung biomechanical models are important for understanding and characterizing lung anatomy and physiology. A key parameter of biomechanical modeling is the underlying tissue elasticity distribution. While human lung elasticity estimations do not have ground truths, model consistency checks can and should be employed to gauge the stability of the estimation techniques. This work proposes such a consistency check using a set of 10 subjects. METHODS: We hypothesize that lung dynamics will be stable over a 2-3 min time period and that this stability can be employed to check biomechanical estimation stability. For this purpose, two sets of 12 fast helical free breathing computed tomography scans (FHFBCT) were acquired back-to-back for each of the subjects. A published breathing motion model [five-dimensional CT (5DCT)] was generated from each set. Both of the models were used to generate two biomechanical modeling input sets: (a) The lung geometry at the end-exhalation, and (b) the voxel displacement map that mapped the end-exhalation lung geometry with the end-inhalation lung geometry. Finite element biomechanical lung models were instantiated using the end-exhalation lung geometries. The models included voxel-specific lung tissue elasticity values and were optimized using a gradient search approach until the biomechanical model-generated displacement maps matched those of the 5DCT voxel displacement maps. Finally, the two elasticity distributions associated with each of the patient 5DCTs were quantitatively compared. Because the end-exhalation geometries differed slightly between the two scan datasets, the elasticity distributions were deformably mapped to one of the exhalation datasets. RESULTS: For the 10 patients, on average, 90% of parenchymal voxels had <2 kPa Young's modulus difference between the two estimations, with a mean voxel difference of only 0.6 kPa. Similarly, 97% of the parenchymal voxels had <2 mm displacement difference between the two models with a mean difference of 0.48 mm. Furthermore, overlapping elasticity histograms for voxels between -600 and -900 HU (parenchymal tissues) showed that the histograms were consistent between the two estimations. CONCLUSION: In this paper, we demonstrated that biomechanical lung models can be consistently estimated when using motion-model based imaging datasets, even though the models were created from scans acquired at different breaths.

Practical Safety Considerations for Integration of Magnetic Resonance Imaging in Radiation Therapy.

Interest in integrating magnetic resonance imaging (MRI) in radiation therapy (RT) practice has increased dramatically in recent years owing to its unique advantages such as excellent soft tissue contrast and capability of measuring biological properties. Continuous real-time imaging for intrafractional motion tracking without ionizing radiation serves as a particularly attractive feature for applications in RT. Despite its many advantages, the integration of MRI in RT workflows is not straightforward, with many unmet needs. MR safety remains one of the key challenges and concerns in the clinical implementation of MR simulators and MR-guided radiation therapy systems in radiation oncology. Most RT staff are not accustomed to working in an environment with a strong magnetic field. There are specific requirements in RT that are different from diagnostic applications. A large variety of implants and devices used in routine RT practice do not have clear MR safety labels. RT-specific imaging pulse sequences focusing on fast acquisition, high spatial integrity, and continuous, real-time acquisition require additional MR safety testing and evaluation. This article provides an overview of MR safety tailored toward RT staff, followed by discussions on specific requirements and challenges associated with MR safety in the RT environment. Strategies and techniques for developing an MR safety program specific to RT are presented and discussed.

Feasibility of deriving a novel imaging biomarker based on patient-specific lung elasticity for characterizing the degree of COPD in lung SBRT patients.

OBJECTIVE:: Lung tissue elasticity is an effective spatial representation for Chronic Obstructive Pulmonary Disease phenotypes and pathophysiology. We investigated a novel imaging biomarker based on the voxel-by-voxel distribution of lung tissue elasticity. Our approach combines imaging and biomechanical modeling to characterize tissue elasticity. METHODS:: We acquired 4DCT images for 13 lung cancer patients with known COPD diagnoses based on GOLD 2017 criteria. Deformation vector fields (DVFs) from the deformable registration of end-inhalation and end-exhalation breathing phases were taken to be the ground-truth. A linear elastic biomechanical model was assembled from end-exhalation datasets with a density-guided initial elasticity distribution. The elasticity estimation was formulated as an iterative process, where the elasticity was optimized based on its ability to reconstruct the ground-truth. An imaging biomarker (denoted YM1-3) derived from the optimized elasticity distribution, was compared with the current gold standard, RA950 using confusion matrix and area under the receiver operating characteristic (AUROC) curve analysis. RESULTS:: The estimated elasticity had 90 % accuracy when representing the ground-truth DVFs. The YM1-3 biomarker had higher diagnostic accuracy (86% vs 71 %), higher sensitivity (0.875 vs 0.5), and a higher AUROC curve (0.917 vs 0.875) as compared to RA950. Along with acting as an effective spatial indicator of lung pathophysiology, the YM1-3 biomarker also proved to be a better indicator for diagnostic purposes than RA950. CONCLUSIONS:: Overall, the results suggest that, as a biomarker, lung tissue elasticity will lead to new end points for clinical trials and new targeted treatment for COPD subgroups. ADVANCES IN KNOWLEDGE:: The derivation of elasticity information directly from 4DCT imaging data is a novel method for performing lung elastography. The work demonstrates the need for a mechanics-based biomarker for representing lung pathophysiology.

Fast, Low-Dose Megavoltage-Topogram Localization on TomoTherapy: Initial Clinical Experience With Mesothelioma Patients.

PURPOSE: This study aimed to evaluate the potential of megavoltage-topogram (MV-topogram)-based alignment as an alternative to megavoltage computed tomography (MVCT) in reducing setup time and imaging dose for patients with malignant pleural mesothelioma who are receiving TomoTherapy. METHODS AND MATERIALS: Twelve patients were enrolled in an ongoing institutional review board approved clinical trial at our institute. Patients were set up with a clinical protocol using red lasers. Anteroposterior (AP) and lateral (LAT) MV-topograms were acquired using gantry angles of 0°/90° with a 1 mm collimator opening, all multileaf collimator leaves open, a couch speed of 4 cm/s, and a 12.5-second scanning time. Routine MVCT scans were performed immediately afterward. The MV-topograms were reconstructed and enhanced using contrast-limited adaptive histogram equalization. Anteroposterior and LAT kilovoltage digital reconstructed topogram images were reconstructed based on TomoTherapy geometry from computed tomography simulation scans. Registrations between MV-topograms and kilovoltage-digital reconstructed topogram images were performed manually, and patients' daily shifts were recorded. Results were compared against the corresponding daily MVCT shifts. MV-topogram and MVCT doses were measured and recorded using an ion chamber on a cheese phantom with depths between 1 and 14 cm, as well as the times required to acquire the 2 image modalities. RESULTS: The mean and standard deviation of shift discrepancies between MV-topogram and MVCT were 0.74 ± 2.08, -0.09 ± 4.46, and 0.45 ± 3.57 mm in the LAT, longitudinal, and vertical directions, respectively. The MVCT imaging doses measured were 14.74 to 26.92 times higher than the MV-topogram doses, depending on depth. On average, MV-topograms with a mean scan length of 50 cm achieved a 5-fold image acquisition time savings over MVCT, with a mean scan length of 38 cm. CONCLUSIONS: MV-topograms has the potential to provide alignment performance equivalent to that of MVCT for patients with mesothelioma, with a significant reduction in imaging dose and acquisition time.

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.

Reconstruction of a high-quality volumetric image and a respiratory motion model from patient CBCT projections.

PURPOSE: To develop and evaluate a method of reconstructing a patient- and treatment day- specific volumetric image and motion model from free-breathing cone-beam projections and respiratory surrogate measurements. This Motion-Compensated Simultaneous Algebraic Reconstruction Technique (MC-SART) generates and uses a motion model derived directly from the cone-beam projections, without requiring prior motion measurements from 4DCT, and can compensate for both inter- and intrabin deformations. The motion model can be used to generate images at arbitrary breathing points, which can be used for estimating volumetric images during treatment delivery. METHODS: The MC-SART was formulated using simultaneous image reconstruction and motion model estimation. For image reconstruction, projections were first binned according to external surrogate measurements. Projections in each bin were used to reconstruct a set of volumetric images using MC-SART. The motion model was estimated based on deformable image registration between the reconstructed bins, and least squares fitting to model parameters. The model was used to compensate for motion in both projection and backprojection operations in the subsequent image reconstruction iterations. These updated images were then used to update the motion model, and the two steps were alternated between. The final output is a volumetric reference image and a motion model that can be used to generate images at any other time point from surrogate measurements. RESULTS: A retrospective patient dataset consisting of eight lung cancer patients was used to evaluate the method. The absolute intensity differences in the lung regions compared to ground truth were 50.8 ± 43.9 HU in peak exhale phases (reference) and 80.8 ± 74.0 in peak inhale phases (generated). The 50th percentile of voxel registration error of all voxels in the lung regions with >5 mm amplitude was 1.3 mm. The MC-SART was also applied to measured patient cone-beam projections acquired with a linac-mounted CBCT system. Results from this patient data demonstrate the feasibility of MC-SART and showed qualitative image quality improvements compared to other state-of-the-art algorithms. CONCLUSION: We have developed a simultaneous image reconstruction and motion model estimation method that uses Cone-beam computed tomography (CBCT) projections and respiratory surrogate measurements to reconstruct a high-quality reference image and motion model of a patient in treatment position. The method provided superior performance in both HU accuracy and positional accuracy compared to other existing methods. The resultant reference image and motion model can be combined with respiratory surrogate measurements to generate volumetric images representing patient anatomy at arbitrary time points.

Estimation and validation of patient-specific high-resolution lung elasticity derived from 4DCT.

PURPOSE: Lung diseases are commonly associated with changes in lung tissue's biomechanical properties. Functional imaging techniques, such as elastography, have shown great promise in measuring tissue's biomechanical properties, which could expand the utility and effectiveness of radiotherapy treatment planning. We present a novel methodology for characterizing a key biomechanical property, parenchymal elasticity, derived solely from 4DCT datasets. METHODS: Specifically, end-inhalation and end-exhalation breathing phases of the 4DCT datasets were deformably registered and the resulting displacement maps were considered to be ground-truth. A mid-exhalation image was also prepared for verification purposes. A GPU-based biomechanical model was then generated from the patient end-exhalation dataset and used as a forward model to iteratively solve for the elasticity distribution. Displacements at the surface of the lungs were applied as boundary constraints for the model-guided tissue elastography, while the inner voxels were allowed to deform according to the linear elastic forces within the biomechanical model. A convergence criteria of 10% maximum deformation was employed for the iterative process. RESULTS: The lung tissue elasticity estimation was documented for a set of 15 4DCT patient datasets. Maximum lung deformations were observed to be between 6 and 31 mm. Our results showed that, on average, 89.91 ± 4.85% convergence was observed. A validation study consisting of mid-exhalation breathing phases illustrated an accuracy of 87.13 ± 10.62%. Structural similarity, normalized cross-correlation, and mutual information were used to quantify the degree of similarity between the following image pairs: (a) the model-generated end-exhalation and ground-truth end-exhalation, and (b) model-generated mid-exhalation images and ground-truth mid-exhalation. CONCLUSIONS: Overall, the results suggest that the lung elasticity can be measured with approximately 90% convergence using routinely acquired clinical 4DCT scans, indicating the potential for a lung elastography implementation within the radiotherapy clinical workflow. The regional lung elasticity found here can lead to improved tissue sparing radiotherapy treatment plans, and more precise monitoring of treatment response.

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.

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.