Faster and lower dose imaging: evaluating adaptive, constant gantry velocity and angular separation in fast low-dose 4D cone beam CT imaging.

BACKGROUND: The adoption of four-dimensional cone beam computed tomography (4DCBCT) for image-guided lung cancer radiotherapy is increasing, especially for hypofractionated treatments. However, the drawbacks of 4DCBCT include long scan times (∼240 s), inconsistent image quality, higher imaging dose than necessary, and streaking artifacts. With the emergence of linear accelerators that can acquire 4DCBCT scans in a short period of time (9.2 s) there is a need to examine the impact that these very fast gantry rotations have on 4DCBCT image quality. PURPOSE: This study investigates the impact of gantry velocity and angular separation between x-ray projections on image quality and its implication for fast low-dose 4DCBCT with emerging systems, such as the Varian Halcyon that provide fast gantry rotation and imaging. Large and uneven angular separation between x-ray projections is known to reduce 4DCBCT image quality through increased streaking artifacts. However, it is not known when angular separation starts degrading image quality. The study assesses the impact of constant and adaptive gantry velocity and determines the level when angular gaps impair image quality using state-of-the-art reconstruction methods. METHODS: This study considers fast low-dose 4DCBCT acquisitions (60-80 s, 200-projection scans). To assess the impact of adaptive gantry rotations, the angular position of x-ray projections from adaptive 4DCBCT acquisitions from a 30-patient clinical trial were analyzed (referred to as patient angular gaps). To assess the impact of angular gaps, variable and static angular gaps (20°, 30°, 40°) were introduced into evenly separated 200 projections (ideal angular separation). To simulate fast gantry rotations, which are on emerging linacs, constant gantry velocity acquisitions (9.2 s, 60 s, 120 s, 240 s) were simulated by sampling x-ray projections at constant intervals using the patient breathing traces from the ADAPT clinical trial (ACTRN12618001440213). The 4D Extended Cardiac-Torso (XCAT) digital phantom was used to simulate projections to remove patient-specific image quality variables. Image reconstruction was performed using Feldkamp-Davis-Kress (FDK), McKinnon-Bates (MKB), and Motion-Compensated-MKB (MCMKB) algorithms. Image quality was assessed using Structural Similarity-Index-Measure (SSIM), Contrast-to-Noise-Ratio (CNR), Signal-to-Noise-Ratio (SNR), Tissue-Interface-Width-Diaphragm (TIW-D), and Tissue-Interface-Width-Tumor (TIW-T). RESULTS: Patient angular gaps and variable angular gap reconstructions produced similar results to ideal angular separation reconstructions, while static angular gap reconstructions produced lower image quality metrics. For MCMKB-reconstructions, average patient angular gaps produced SSIM-0.98, CNR-13.6, SNR-34.8, TIW-D-1.5 mm, and TIW-T-2.0 mm, static angular gap 40° produced SSIM-0.92, CNR-6.8, SNR-6.7, TIW-D-5.7 mm, and TIW-T-5.9 mm and ideal produced SSIM-1.00, CNR-13.6, SNR-34.8, TIW-D-1.5 mm, and TIW-T-2.0 mm. All constant gantry velocity reconstructions produced lower image quality metrics than ideal angular separation reconstructions regardless of the acquisition time. Motion compensated reconstruction (MCMKB) produced the highest contrast images with low streaking artifacts. CONCLUSION: Very fast 4DCBCT scans can be acquired provided that the entire scan range is adaptively sampled, and motion-compensated reconstruction is performed. Importantly, the angular separation between x-ray projections within each individual respiratory bin had minimal effect on the image quality of fast low-dose 4DCBCT imaging. The results will assist the development of future 4DCBCT acquisition protocols that can now be achieved in very short time frames with emerging linear accelerators.

The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients.

PURPOSE: Multiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. METHODS/MATERIALS: The KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. RESULTS: The KIM localisation accuracy was 0.2±0.9 mm (left-right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and -0.1◦±0.8◦ (left-right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. CONCLUSIONS: This work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

X-ray source arrays for volumetric imaging during radiotherapy treatment.

This work presents a novel hardware configuration for radiotherapy systems to enable fast 3D X-ray imaging before and during treatment delivery. Standard external beam radiotherapy linear accelerators (linacs) have a single X-ray source and detector located at ± 90° from the treatment beam respectively. The entire system can be rotated around the patient acquiring multiple 2D X-ray images to create a 3D cone-beam Computed Tomography (CBCT) image before treatment delivery to ensure the tumour and surrounding organs align with the treatment plan. Scanning with a single source is slow relative to patient respiration or breath holds and cannot be performed during treatment delivery, limiting treatment delivery accuracy in the presence of patient motion and excluding some patients from concentrated treatment plans that would be otherwise expected to have improved outcomes. This simulation study investigated whether recent advances in carbon nanotube (CNT) field emission source arrays, high frame rate (60 Hz) flat panel detectors and compressed sensing reconstruction algorithms could circumvent imaging limitations of current linacs. We investigated a novel hardware configuration incorporating source arrays and high frame rate detectors into an otherwise standard linac. We investigated four potential pre-treatment scan protocols that could be achieved in a 17 s breath hold or 2-10 1 s breath holds. Finally, we demonstrated for the first time volumetric X-ray imaging during treatment delivery by using source arrays, high frame rate detectors and compressed sensing. Image quality was assessed quantitatively over the CBCT geometric field of view as well as across each axis through the tumour centroid. Our results demonstrate that source array imaging enables larger volumes to be imaged with acquisitions as short as 1 s albeit with reduced image quality arising from lower photon flux and shorter imaging arcs.

Thoracic motion-compensated cone-beam computed tomography in under 20 seconds on a fast-rotating linac: A simulation study.

BACKGROUND: Rapid kV cone-beam computed tomography (CBCT) scans are achievable in under 20 s on select linear accelerator systems to generate volumetric images in three dimensions (3D). Daily pre-treatment four-dimensional CBCT (4DCBCT) is recommended in image-guided lung radiotherapy to mitigate the detrimental effects of respiratory motion on treatment quality. PURPOSE: To demonstrate the potential for thoracic 4DCBCT reconstruction using projection data that was simulated using a clinical rapid 3DCBCT acquisition protocol. METHODS: We simulated conventional (1320 projections over 4 min) and rapid (491 projections over 16.6 s) CBCT acquisitions using 4D computed tomography (CT) volumes of 14 lung cancer patients. Conventional acquisition data were reconstructed using the 4D Feldkamp-Davis-Kress (FDK) algorithm. Rapid acquisition data were reconstructed using 3DFDK, 4DFDK, and Motion-Compensated FDK (MCFDK). Image quality was evaluated using Contrast-to-Noise Ratio (CNR), Tissue Interface Width (TIW), Root-Mean-Square Error (RMSE), and Structural SIMilarity (SSIM). RESULTS: The conventional acquisition 4DFDK reconstructions had median phase averaged CNR, TIW, RMSE, and SSIM of 2.96, 8.02 mm, 83.5, and 0.54, respectively. The rapid acquisition 3DFDK reconstructions had median CNR, TIW, RMSE, and SSIM of 2.99, 13.6 mm, 112, and 0.44 respectively. The rapid acquisition MCFDK reconstructions had median phase averaged CNR, TIW, RMSE, and SSIM of 2.98, 10.2 mm, 103, and 0.46, respectively. Rapid acquisition 4DFDK reconstruction quality was insufficient for any practical use due to sparse angular projection sampling. CONCLUSIONS: Results suggest that 4D motion-compensated reconstruction of rapid acquisition thoracic CBCT data are feasible with image quality approaching conventional acquisition CBCT data reconstructed using standard 4DFDK.

The dosimetric error due to uncorrected tumor rotation during real-time adaptive prostate stereotactic body radiation therapy.

BACKGROUND: During prostate stereotactic body radiation therapy (SBRT), prostate tumor translational motion may deteriorate the planned dose distribution. Most of the major advances in motion management to date have focused on correcting this one aspect of the tumor motion, translation. However, large prostate rotation up to 30° has been measured. As the technological innovation evolves toward delivering increasingly precise radiotherapy, it is important to quantify the clinical benefit of translational and rotational motion correction over translational motion correction alone. PURPOSE: The purpose of this work was to quantify the dosimetric impact of intrafractional dynamic rotation of the prostate measured with a six degrees-of-freedom tumor motion monitoring technology. METHODS: The delivered dose was reconstructed including (a) translational and rotational motion and (b) only translational motion of the tumor for 32 prostate cancer patients recruited on a 5-fraction prostate SBRT clinical trial. Patients on the trial received 7.25 Gy in a treatment fraction. A 5 mm clinical target volume (CTV) to planning target volume (PTV) margin was applied in all directions except the posterior direction where a 3 mm expansion was used. Prostate intrafractional translational motion was managed using a gating strategy, and any translation above the gating threshold was corrected by applying an equivalent couch shift. The residual translational motion is denoted as T r e s $T_{res}$ . Prostate intrafractional rotational motion R u n c o r r $R_{uncorr}$ was recorded but not corrected. The dose differences from the planned dose due to T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ , ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and due to T r e s $T_{res}$ alone, ΔD( T r e s $T_{res}$ ), were then determined for CTV D98, PTV D95, bladder V6Gy, and rectum V6Gy. The residual dose error due to uncorrected rotation, R u n c o r r $R_{uncorr}$ was then quantified: Δ D R e s i d u a l $\Delta D_{Residual}$ = ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) - ΔD( T res ${T}_{\textit{res}}$ ). RESULTS: Fractional data analysis shows that the dose differences from the plan (both ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and ΔD( T r e s $T_{res}$ )) for CTV D98 was less than 5% in all treatment fractions. ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) was larger than 5% in one fraction for PTV D95, in one fraction for bladder V6Gy, and in five fractions for rectum V6Gy. Uncorrected rotation, R u n c o r r $R_{uncorr}$ induced residual dose error, Δ D R e s i d u a l $\Delta D_{Residual}$ , resulted in less dose to CTV and PTV in 43% and 59% treatment fractions, respectively, and more dose to bladder and rectum in 51% and 53% treatment fractions, respectively. The cumulative dose over five fractions, ∑D( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and ∑D( T r e s $T_{res}$ ), was always within 5% of the planned dose for all four structures for every patient. CONCLUSIONS: The dosimetric impact of tumor rotation on a large prostate cancer patient cohort was quantified in this study. These results suggest that the standard 3-5 mm CTV-PTV margin was sufficient to account for the intrafraction prostate rotation observed for this cohort of patients, provided an appropriate gating threshold was applied to correct for translational motion. Residual dose errors due to uncorrected prostate rotation were small in magnitude, which may be corrected using different treatment adaptation strategies to further improve the dosimetric accuracy.

CArdiac and REspiratory adaptive Computed Tomography (CARE-CT): a proof-of-concept digital phantom study.

Current respiratory 4DCT imaging for high-dose rate thoracic radiotherapy treatments are negatively affected by the complex interaction of cardiac and respiratory motion. We propose an imaging method to reduce artifacts caused by thoracic motion, CArdiac and REspiratory adaptive CT (CARE-CT), that monitors respiratory motion and ECG signals in real-time, triggering CT acquisition during combined cardiac and respiratory bins. Using a digital phantom, conventional 4DCT and CARE-CT acquisitions for nineteen patient-measured physiological traces were simulated. Ten respiratory bins were acquired for conventional 4DCT scans and ten respiratory bins during cardiac diastole were acquired for CARE-CT scans. Image artifacts were quantified for 10 common thoracic organs at risk (OAR) substructures using the differential normalized cross correlation between axial slices (ΔNCC), mean squared error (MSE) and sensitivity. For all images, on average, CARE-CT improved the ΔNCC for 18/19 and the MSE and sensitivity for all patient traces. The ΔNCC was reduced for all cardiac OARs (mean reduction 21%). The MSE was reduced for all OARs (mean reduction 36%). In the digital phantom study, the average scan time was increased from 1.8 ± 0.4 min to 7.5 ± 2.2 min with a reduction in average beam on time from 98 ± 28 s to 45 s using CARE-CT compared to conventional 4DCT. The proof-of-concept study indicates the potential for CARE-CT to image the thorax in real-time during the cardiac and respiratory cycle simultaneously, to reduce image artifacts for common thoracic OARs.

System requirements to improve adaptive 4-dimensional computed tomography (4D CT) imaging.

Four-Dimensional Computed Tomography (4D CT) is of increasing importance in stereotactic body radiotherapy (SBRT) treatments affected by respiratory motion. However, 4D CT images are commonly impacted by irregular breathing, causing image artifacts that can propagate through to treatment, negatively effecting local control. REspiratory Adaptive CT (REACT) is a real-time gating method demonstrated to reduce motion artifacts by avoiding imaging during irregular respiration. Despite artifact reduction seen throughin silicoand clinical phantom-based studies, REACT has not been able to remove all artifacts. Here, we explore several hardware and software latencies (gantry rotation time, couch shifts, acquisition delays and phase calculation method) inherently linked to REACT and 4D CT in general and investigate their contribution to artifacts beyond those caused by irregular breathing. Imaging was simulated using the digital extended cardiac-torso (XCAT) phantom for fifty patient-measured respiratory traces. Imaging protocols included conventional cine 4D CT and five REACT scans with systematically varied parameters to test the effect of different latencies on artifacts. Artifacts were quantified by comparing the image normalized cross correlation across couch transition points and determining the volume error compared to a static phantom ground truth both as a total error and individually across pixel rows in the main plane of motion. Artifacts were determined for each lung, the whole heart and lung tumour and were compared back to conventional 4D CT and REACT with standard clinical scanning parameters. The gantry rotation time and acquisition delay were found to have the largest impact on reducing image artifacts and should be the focus of future development. The phase calculation method was also found to influence motion artifacts and should potentially be assessed on a patient-to-patient basis. Finally, the correlation between an increase in artifacts and baseline drift suggests that longer scan times allowing drift to occur may impact image quality.

Generating patient-matched 3D-printed pedicle screw and laminectomy drill guides from Cone Beam CT images: Studies in ovine and porcine cadavers.

BACKGROUND: The emergence of robotic Cone Beam Computed Tomography (CBCT) imaging systems in trauma departments has enabled 3D anatomical assessment of musculoskeletal injuries, supplementing conventional 2D fluoroscopic imaging for examination, diagnosis, and treatment planning. To date, the primary focus has been on trauma sites in the extremities. PURPOSE: To determine if CBCT images can be used during the treatment planning process in spinal instrumentation and laminectomy procedures, allowing accurate 3D-printed pedicle screw and laminectomy drill guides to be generated for the cervical and thoracic spine. METHODS: The accuracy of drill guides generated from CBCT images was assessed using animal cadavers (ovine and porcine). Preoperative scans were acquired using a robotic CBCT C-arm system, the Siemens ARTIS pheno (Siemens Healthcare, GmbH, Germany). The CBCT images were imported into 3D-Slicer version 4.10.2 (www.slicer.org) where vertebral models and specific guides were developed and subsequently 3D-printed. In the ovine cadaver, 11 pedicle screw guides from the T1-T5 and T7-T12 vertebra and six laminectomy guides from the C2-C7 vertebra were planned and printed. In the porcine cadaver, nine pedicle screw guides from the C3-T4 vertebra were planned and printed. For the pedicle screw guides, accuracy was assessed by three observers according to pedicle breach via the Gertzbein-Robbins grading system as well as measured mean axial and sagittal screw error via postoperative CBCT and CT scans. For the laminectomies, the guides were designed to leave 1 mm of lamina. The average thickness of the lamina at the mid-point was used to assess the accuracy of the guides, measured via postoperative CBCT and CT scans from three observers. For all measurements, the intraclass correlation coefficient (ICC) was calculated to determine observer reliability. RESULTS: Compared with the planned screw angles for both the ovine and porcine procedures (n = 32), the mean axial and sagittal screw error measured on the postoperative CBCT scans from three observers were 3.9 ± 1.9° and 1.8 ± 0.8°, respectively. The ICC among the observes was 0.855 and 0.849 for the axial and sagittal measurements, respectively, indicating good reliability. In the ovine cadaver, directly comparing the measured axial and sagittal screw angle of the visible screws (n = 14) in the postoperative CBCT and conventional CT scans from three observers revealed an average difference 1.9 ± 1.0° in axial angle and 1.8 ± 1.0° in the sagittal angle. The average thickness of the lamina at the middle of each vertebra, as measured on-screen in the postoperative CBCT scans by three observes was 1.6 ± 0.2 mm. The ICC among observers was 0.693, indicating moderate reliability. No lamina breaches were observed in the postoperative images. CONCLUSION: Here, CBCT images have been used to generate accurate 3D-printed pedicle screw and laminectomy drill guides for use in the cervical and thoracic spine. The results demonstrate sufficient precision compared with those previously reported, generated from standard preoperative CT and MRI scans, potentially expanding the treatment planning capabilities of robotic CBCT imaging systems in trauma departments and operating rooms.

Reducing 4DCBCT imaging dose and time: exploring the limits of adaptive acquisition and motion compensated reconstruction.

This study investigates the dose and time limits of adaptive 4DCBCT acquisitions (adaptive-acquisition) compared with current conventional 4DCBCT acquisition (conventional-acquisition). We investigate adaptive-acquisitions as low as 60 projections (∼25 s scan, 6 projections per respiratory phase) in conjunction with emerging image reconstruction methods. 4DCBCT images from 20 patients recruited into the adaptive CT acquisition for personalized thoracic imaging clinical study (NCT04070586) were resampled to simulate faster and lower imaging dose acquisitions. All acquisitions were reconstructed using Feldkamp-Davis-Kress (FDK), McKinnon-Bates (MKB), motion compensated FDK (MCFDK), motion compensated MKB (MCMKB) and simultaneous motion estimation and image reconstruction (SMEIR) algorithms. All reconstructions were compared against conventional-acquisition 4DFDK-reconstruction using Structural SIMilarity Index (SSIM), signal-to-noise ratio (SNR), contrast-to-noise-ratio (CNR), tissue interface sharpness diaphragm (TIS-D), tissue interface sharpness tumor (TIS-T) and center of mass trajectory (COMT) for difference in diaphragm and tumor motion. All reconstruction methods using 110-projection adaptive-acquisition (11 projections per respiratory phase) had a SSIM of greater than 0.92 relative to conventional-acquisition 4DFDK-reconstruction. Relative to conventional-acquisition 4DFDK-reconstruction, 110-projection adaptive-acquisition MCFDK-reconstructions images had 60% higher SNR, 10% higher CNR, 30% higher TIS-T and 45% higher TIS-D on average. The 110-projection adaptive-acquisition SMEIR-reconstruction images had 123% higher SNR, 90% higher CNR, 96% higher TIS-T and 60% higher TIS-D on average. The difference in diaphragm and tumor motion compared to conventional-acquisition 4DFDK-reconstruction was within submillimeter accuracy for all acquisition reconstruction methods. Adaptive-acquisitions resulted in faster scans with lower imaging dose and equivalent or improved image quality compared to conventional-acquisition. Adaptive-acquisition with motion compensated-reconstruction enabled scans with as low as 110 projections to deliver acceptable image quality. This translates into 92% lower imaging dose and 80% less scan time than conventional-acquisition.

A real-time IGRT method using a Kalman filter framework to extract 3D positions from 2D projections.

Purpose.To estimate 3D prostate motion in real-time during irradiation from 2D prostate positions acquired from a kV imager on a standard linear accelerator utilising a Kalman filter (KF) framework. The advantage of this novel method is threefold: (1) eliminating the need of an initial learning period, therefore reducing patient imaging dose, (2) more robust against measurement noise and (3) more computationally efficient. In this paper, the novel KF method was evaluatedin silicousing patients' 3D prostate motion and simulated 2D projections.Methods.A KF framework was implemented to estimate 3D motion from 2D projection measurements in real-time during prostate cancer treatments. The noise covariance matrix was adaptively estimated from the previous 10 measurements. This method did not require an initial learning period as the KF process distribution was initialised using a population covariance matrix. This method was evaluated using a ground-truth motion dataset of 17 prostate cancer patients (536 trajectories) measured with electromagnetic transponders. 3D motion was projected onto a rotating imager (SID = 180 cm) (pixel size = 0.388 mm) and rotation speed of 6°/s and 2°/s to simulate VMAT treatments. Gantry-varying additive random noise (≤5 mm) was added to ground-truth measurements to simulate segmentation error and image quality degradation due to the patient's pelvic bones. For comparison, motion was also estimated using the clinically implemented Gaussian probability density function (PDF) method initialised with 600 projections.Results.Without noise, the 3D root mean square-errors (3D RMSEs) of motion estimated by the KF method were 0.4 ± 0.1 mm and 0.3 ± 0.2 mm for 2°/s and 6°/s gantry rotation, respectively. With noise, 3D RMSEs of KF estimated motion were 1.1 ± 0.1 mm for both slow and fast gantry rotation scenarios. In comparison, using a Gaussian PDF method, with noise, 3D RMSE was 2 ± 0.1 mm for both gantry rotation scenarios.Conclusion.This work presents a fast and accurate method for real-time 2D to 3D motion estimation using a KF approach to handle the random-walk component of prostate cancer motion. This method has sub-mm accuracy and is highly robust against measurement noise.

The first-in-human implementation of adaptive 4D cone beam CT for lung cancer radiotherapy: 4DCBCT in less time with less dose.

BACKGROUND AND PURPOSE: We present the first implementation of Adaptive 4D cone beam CT (4DCBCT) that adapts the image hardware (gantry rotation speed and kV projections) in response to the patient's real-time respiratory signal. Adaptive 4DCBCT was applied on lung cancer patients to reduce the scan time and imaging dose in the ADaptive CT Acquisition for Personalised Thoracic imaging (ADAPT) trial. MATERIALS AND METHODS: The ADAPT technology measures the patient's real-time respiratory signal and uses mathematical optimisation and external circuitry attached to the linear accelerator to modulate the gantry rotation speed and kV projection rate to reduce scan times and imaging dose. For each patient, ADAPT scans were acquired on two treatment fractions and reconstructed with a motion compensated reconstruction algorithm and compared to the current state-of-the-art four-minute 4DCBCT acquisition (conventional 4DCBCT). We report on the scan time, imaging dose and image quality for the first four adaptive 4DCBCT patients. RESULTS: The ADAPT imaging dose was reduced by 85% and scan times were 73 ± 12 s representing a 70% reduction compared to the 240 s conventional 4DCBCT scan. The contrast-to-noise ratio was improved from 9.2 ± 3.9 with conventional 4DCBCT to 11.7 ± 4.1 with ADAPT. DISCUSSION: The ADAPT trial represents the first time that gantry rotation speed and projection acquisition have been adapted and optimised in real-time in response to changes in the patient's breathing. ADAPT demonstrates substantially reduced scan times and imaging dose for clinical 4DCBCT imaging that could enable more efficient and optimised lung cancer radiotherapy.

First experimental evaluation of multi-target multileaf collimator tracking during volumetric modulated arc therapy for locally advanced prostate cancer.

PURPOSE: Locally advanced and oligometastatic cancer patients require radiotherapy treatment to multiple independently moving targets. There is no existing commercial solution that can simultaneously track and treat multiple targets. This study experimentally implemented and evaluated a real-time multi-target tracking system for locally advanced prostate cancer. METHODS: Real-time multi-target MLC tracking was integrated with 3D x-ray image guidance on a standard linac. Three locally advanced prostate cancer treatment plans were delivered to a static lymph node phantom and dynamic prostate phantom that reproduced three prostate trajectories. Treatments were delivered using multi-target MLC tracking, single-target MLC tracking, and no tracking. Doses were measured using Gafchromic film placed in the dynamic and static phantoms. Dosimetric error was quantified by the 2%/2 mm gamma failure rate. Geometric error was evaluated as the misalignment between target and aperture positions. The multi-target tracking system latency was measured. RESULTS: The mean (range) gamma failure rates for the prostate and lymph nodes, were 18.6% (5.2%, 28.5%) and 7.5% (1.1%, 13.7%) with multi-target tracking, 7.9% (0.7%, 15.4%) and 37.8% (18.0%, 57.9%) with single-target tracking, and 38.1% (0.6%, 75.3%) and 37.2% (29%, 45.3%) without tracking. Multi-target tracking had the lowest geometric error with means and standard deviations within 0.2 ± 1.5 for the prostate and 0.0 ± 0.3 mm for the lymph nodes. The latency was 730 ± 20 ms. CONCLUSION: This study presented the first experimental implementation of multi-target tracking to independently track prostate and lymph node displacement during VMAT. Multi-target tracking reduced dosimetric and geometric errors compared to single-target tracking and no tracking.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

The adaptation and investigation of cone-beam CT reconstruction algorithms for horizontal rotation fixed-gantry scans of rabbits.

Fixed-gantry radiation therapy has been proposed as a low-cost alternative to the conventional rotating-gantry radiation therapy, that may help meet the rising global treatment demand. Fixed-gantry systems require gravitational motion compensated reconstruction algorithms to produce cone-beam CT (CBCT) images of sufficient quality for image guidance. The aim of this work was to adapt and investigate five CBCT reconstruction algorithms for fixed-gantry CBCT images. The five algorithms investigated were Feldkamp-Davis-Kress (FDK), prior image constrained compressed sensing (PICCS), gravitational motion compensated FDK (GMCFDK), motion compensated PICCS (MCPICCS) (a novel CBCT reconstruction algorithm) and simultaneous motion estimation and iterative reconstruction (SMEIR). Fixed-gantry and rotating-gantry CBCT scans were acquired of 3 rabbits, with the rotating-gantry scans used as a reference. Projections were sorted into rotation bins, based on the angle of rotation of the rabbit during image acquisition. The algorithms were compared using the structural similarity index measure root mean square error, and reconstruction time. Evaluation of the reconstructed volumes showed that, when compared with the reference rotating-gantry volume, the conventional FDK algorithm did not accurately reconstruct fixed-gantry CBCT scans. Whilst the PICCS reconstruction algorithm reduced some motion artefacts, the motion estimation reconstruction methods (GMCFDK, MCPICCS and SMEIR) were able to greatly reduce the effect of motion artefacts on the reconstructed volumes. This finding was verified quantitatively, with GMCFDK, MCPICCS and SMEIR reconstructions having RMSE 17%-19% lower and SSIM 1% higher than a conventional FDK. However, all motion compensated fixed-gantry CBCT reconstructions had a 56%-61% higher RMSE and 1.5% lower SSIM than FDK reconstructions of conventional rotating-gantry CBCT scans. The results show that motion compensation is required to reduce motion artefacts for fixed-gantry CBCT reconstructions. This paper further demonstrates the feasibility of fixed-gantry CBCT scans, and the ability of CBCT reconstruction algorithms to compensate for motion due to horizontal rotation.

Reducing 4DCBCT scan time and dose through motion compensated acquisition and reconstruction.

Conventional 4DCBCT captures 1320 projections across 4 min. Adaptive 4DCBCT has been developed to reduce imaging dose and scan time. This study investigated reconstruction algorithms that best complement adaptive 4DCBCT acquisition for reducing imaging dose and scan time whilst maintaining or improving image quality compared to conventional 4DCBCT acquisition using real patient data from the first 10 adaptive 4DCBCT patients. Adaptive 4DCBCT was implemented in the ADaptive CT Acquisition for Personalized Thoracic imaging clinical trial. Adaptive 4DCBCT modulates gantry rotation speed and kV acquisition rate in response to the patient's real-time respiratory signal, ensuring even angular spacing between projections at each respiratory phase. We examined the first 10 lung cancer radiotherapy patients that received adaptive 4DCBCT. Fast, 200-projection scans over 60-80 s, and slower, 600-projection scans over ∼240 s, were obtained after routine patient treatment and compared against conventional 4DCBCT acquisition. Adaptive 4DCBCT acquisitions were reconstructed using Feldkamp-Davis-Kress (FDK), McKinnon-Bates (MKB), Motion Compensated FDK (MCFDK) and Motion Compensated MKB (MCMKB) algorithms. Reconstructions were assessed via, Structural SIMilarity (SSIM), Signal-to-Noise-Ratio (SNR), Contrast-to-Noise-Ratio (CNR), Tissue Interface Sharpness of Diaphragm (TIS-D) and Tumor (TIS-T). The 200- and 600-projection adaptive 4DCBCT acquisition corresponded to 85% and 55% reduction in imaging dose, shorter and similar scan times of approximately 90 s and 236 s respectively, compared to conventional 4DCBCT acquisition. 200- and 600-projection adaptive 4DCBCT reconstructions achieved more than 0.900 SSIM relative to conventional 4DCBCT acquisition. Compared to conventional 4DCBCT acquisition, 200-projection adaptive 4DCBCT reconstructions achieved higher SNR, CNR, TIS-T, TIS-D with motion compensated algorithms, MCFDK (208%, 159%, 174%, 247%) and MCMKB (214%, 173%, 266%, 245%) respectively. The 200-projection adaptive 4DCBCT MCFDK- and MCMKB-reconstruction results show image quality improvements are possible even with 85% fewer projections acquired. We established acquisition-reconstruction protocols that provide substantial reductions in imaging time and dose whilst improving image quality.

Pre-treatment and real-time image guidance for a fixed-beam radiotherapy system.

PURPOSE: A radiotherapy system with a fixed treatment beam and a rotating patient positioning system could be smaller, more robust and more cost effective compared to conventional rotating gantry systems. However, patient rotation could cause anatomical deformation and compromise treatment delivery. In this work, we demonstrate an image-guided treatment workflow with a fixed beam prototype system that accounts for deformation during rotation to maintain dosimetric accuracy. METHODS: The prototype system consists of an Elekta Synergy linac with the therapy beam orientated downward and a custom-built patient rotation system (PRS). A phantom that deforms with rotation was constructed and rotated within the PRS to quantify the performance of two image guidance techniques: motion compensated cone-beam CT (CBCT) for pre-treatment volumetric imaging and kilovoltage infraction monitoring (KIM) for real-time image guidance. The phantom was irradiated with a 3D conformal beam to evaluate the dosimetric accuracy of the workflow. RESULTS: The motion compensated CBCT was used to verify pre-treatment position and the average calculated position was within -0.3 ± 1.1 mm of the phantom's ground truth position at 0°. KIM tracked the position of the target in real-time as the phantom was rotated and the average calculated position was within -0.2 ± 0.8 mm of the phantom's ground truth position. A 3D conformal treatment delivered on the prototype system with image guidance had a 3%/2 mm gamma pass rate of 96.3% compared to 98.6% delivered using a conventional rotating gantry linac. CONCLUSIONS: In this work, we have shown that image guidance can be used with fixed-beam treatment systems to measure and account for changes in target position in order to maintain dosimetric coverage during horizontal rotation. This treatment modality could provide a viable treatment option when there insufficient space for a conventional linear accelerator or where the cost is prohibitive.

Minimizing 4DCBCT imaging dose and scan time with Respiratory Motion Guided 4DCBCT: a pre-clinical investigation.

Current conventional 4D Cone Beam Computed Tomography (4DCBCT) imaging is hampered by inconsistent patient breathing that leads to long scan times, reduced image quality and high imaging dose. To address these limitations, Respiratory Motion Guided 4D cone beam computed tomography (RMG-4DCBCT) uses mathematical optimization to adapt the gantry rotation speed and projection acquisition rate in real-time in response to changes in the patient's breathing rate. Here, RMG-4DCBCT is implemented on an Elekta Synergy linear accelerator to determine the minimum achievable imaging dose. 8 patient-measured breathing traces were programmed into a 1D motion stage supporting a 3D-printed anthropomorphic thorax phantom. The respiratory phase and current gantry position were calculated in real-time with the RMG-4DCBCT software, which in turn modulated the gantry rotation speed and suppressed projection acquisition. Specifically, the effect of acquiring 20, 25, 30, 35 and 40 projections/respiratory phase bin RMG scans on scan time and image quality was assessed. Reconstructed image quality was assessed via the contrast-to-noise ratio (CNR) and the Edge Response Width (ERW) metrics. The performance of the system in terms of gantry control accuracy was also assessed via an analysis of the angular separation between adjacent projections. The median CNR increased linearly from 5.90 (20 projections/bin) to 8.39 (40 projections/bin). The ERW did not significantly change from 1.08 mm (20 projections/bin) to 1.07 mm (40 projections/bin), indicating the sharpness is not dependent on the total number of projections acquired. Scan times increased with increasing total projections and slower breathing rates. Across all 40 RMG-4DCBCT scans performed, the average difference in the acquired and desired angular separation between projections was 0.64°. RMG-4DCBCT provides the opportunity to enable fast low-dose 4DCBCT (∼70 s, 200 projections), without compromising on current clinical image quality.

Toward real-time verification for MLC tracking treatments using time-resolved EPID imaging.

PURPOSE: In multileaf collimator (MLC) tracking, the MLC positions from the original treatment plan are continuously modified to account for intrafraction tumor motion. As the treatment is adapted in real time, there is additional risk of delivery errors which cannot be detected using traditional pretreatment dose verification. The purpose of this work is to develop a system for real-time geometric verification of MLC tracking treatments using an electronic portal imaging device (EPID). METHODS: MLC tracking was utilized during volumetric modulated arc therapy (VMAT). During these deliveries, treatment beam images were taken at 9.57 frames per second using an EPID and frame grabber computer. MLC positions were extracted from each image frame and used to assess delivery accuracy using three geometric measures: the location, size, and shape of the radiation field. The EPID-measured field location was compared to the tumor motion measured by implanted electromagnetic markers. The size and shape of the beam were compared to the size and shape from the original treatment plan, respectively. This technique was validated by simulating errors in phantom test deliveries and by comparison between EPID measurements and treatment log files. The method was applied offline to images acquired during the LIGHT Stereotactic Ablative Body Radiotherapy (SABR) clinical trial, where MLC tracking was performed for 17 lung cancer patients. The EPID-based verification results were subsequently compared to post-treatment dose reconstruction. RESULTS: Simulated field location errors were detected during phantom validation tests with an uncertainty of 0.28 mm (parallel to MLC motion) and 0.38 mm (perpendicular), expressed as a root-mean-square error (RMSError ). For simulated field size errors, the RMSError was 0.47 cm2 and field shape changes were detected for random errors with standard deviation ≥ 2.5 mm. For clinical lung SABR deliveries, field location errors of 1.6 mm (parallel MLC motion) and 4.9 mm (perpendicular) were measured (expressed as a full-width-half-maximum). The mean and standard deviation of the errors in field size and shape were 0.0 ± 0.3 cm2 and 0.3 ± 0.1 (expressed as a translation-invariant normalized RMS). No correlation was observed between geometric errors during each treatment fraction and dosimetric errors in the reconstructed dose to the target volume for this cohort of patients. CONCLUSION: A system for real-time delivery verification has been developed for MLC tracking using time-resolved EPID imaging. The technique has been tested offline in phantom-based deliveries and clinical patient deliveries and was used to independently verify the geometric accuracy of the MLC during MLC tracking radiotherapy.

Adapting to the motion of multiple independent targets using multileaf collimator tracking for locally advanced prostate cancer: Proof of principle simulation study.

PURPOSE: For patients with locally advanced cancer, multiple targets are treated simultaneously with radiotherapy. Differential motion between targets can compromise the treatment accuracy, yet there are currently no methods able to adapt to independent target motion. This study developed a multileaf collimator (MLC) tracking algorithm for differential motion adaptation and evaluated it in simulated treatments of locally advanced prostate cancer. METHODS: A multi-target MLC tracking algorithm was developed that consisted of three steps: (a) dividing the MLC aperture into two possibly overlapping sections assigned to the prostate and lymph nodes, (b) calculating the ideally shaped MLC aperture as a union of the individually translated sections, and (c) fitting the MLC positions to the ideal aperture shape within the physical constraints of the MLC leaves. The multi-target tracking method was evaluated and compared with two existing motion management methods: single-target tracking and no tracking. Treatment simulations of six locally advanced prostate cancer patients with three prostate motion traces were performed for all three motion adaptation methods. The geometric error for each motion adaptation method was calculated using the area of overexposure and underexposure of each field. The dosimetric error was estimated by calculating the dose delivered to the prostate, lymph nodes, bladder, rectum, and small bowel using a motion-encoded dose reconstruction method. RESULTS: Multi-target MLC tracking showed an average improvement in geometric error of 84% compared to single-target tracking, and 83% compared to no tracking. Multi-target tracking maintained dose coverage to the prostate clinical target volume (CTV) D98% and planning target volume (PTV) D95% to within 4.8% and 3.9% of the planned values, compared to 1.4% and 0.7% with single-target tracking, and 20.4% and 31.8% with no tracking. With multi-target tracking, the node CTV D95%, PTV D90%, and gross tumor volume (GTV) D95% were within 0.3%, 0.6%, and 0.3% of the planned values, compared to 9.1%, 11.2%, and 21.1% for single-target tracking, and 0.8%, 2.0%, and 3.2% with no tracking. The small bowel V57% was maintained within 0.2% to the plan using multi-target tracking, compared to 8% and 3.5% for single-target tracking and no tracking, respectively. Meanwhile, the bladder and rectum V50% increased by up to 13.6% and 5.2%, respectively, using multi-target tracking, compared to 2.7% and 1.9% for single-target tracking, and 11.2% and 11.5% for no tracking. CONCLUSIONS: A multi-target tracking algorithm was developed and tracked the prostate and lymph nodes independently during simulated treatments. As the algorithm optimizes for target coverage, tracking both targets simultaneously may increase the dose delivered to the organs at risk.

MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

BACKGROUND AND PURPOSE: The purpose of this work is to present the clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung lesions. METHODS AND MATERIALS: Seventeen patients with stage 1 non-small cell lung cancer (NSCLC) or lung metastases were included in a study of electromagnetic transponder-guided MLC tracking for SABR (NCT02514512). Patients had electromagnetic transponders inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5 mm from the end-exhale gross tumor volume (GTV). A clinically approved comparator plan was generated with PTV expanded 5 mm from a 4DCT-derived internal target volume (ITV). Treatment was delivered using a standard linear accelerator to continuously adapt the MLC based on transponder motion. Treated volumes and reconstructed delivered dose were compared between MLC tracking and comparator ITV-based treatment. RESULTS: All seventeen patients were successfully treated with MLC tracking (70 successful fractions). MLC tracking treatment delivery time averaged 8 minutes. The time from the start of CBCT to the end of treatment averaged 22 minutes. The MLC tracking PTV for 16/17 patients was smaller than the ITV-based PTV (range -1.6% to 44% reduction, or -0.6 to 18 cc). Reductions in mean lung dose (27 cGy) and V20Gy (50 cc) were statistically significant (p < 0.02). Reconstruction of treatment doses confirmed a statistically significant improvement in delivered GTV D98% (p < 0.05) from planned dose compared with the ITV-based plans. CONCLUSION: The first treatments with lung MLC tracking have been successfully performed in seventeen SABR patients. MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.