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Open Access Publications from the University of California

Scholarly Works (12 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2018)

Breathing motion in radiotherapy is commonly managed with four-dimensional computed tomography (4DCT). 4DCT datasets consist of multiple breathing-gated images that display motion of the subject’s anatomy over a breathing period. Commercial 4DCT protocols are

susceptible to image artifacts when the subject breathes irregularly. Unlike commercial protocols, model-based 4DCT techniques describe a correspondence between tissue motion and an external signal used as a surrogate for respiratory phase. One such technique, termed ’5DCT,’ uses free-breathing fast helical acquisition and characterizes lung tissue motion as function of five degrees of freedom: x,y, and z position in a reference geometry, breathing amplitude, and breathing rate. The overarching goal of this dissertation is to develop the 5DCT technique for clinical use.

A validation study was conducted involving comparing 5DCT images to commercial 4DCT using an animal model. Reproducible and periodic breathing patterns were achieved through mechanical ventilation and image similarity was quantified using landmark displacement.

Differences in measured tumor motion between 5DCT and commercial 4DCT were examined in a cohort of 20 lung cancer patients. Solutions for the unique challenges of using model model-based techniques clinically, such as appropriate amplitude interval selection and presentation of a quantitative error map, were developed.

A quality management program was developed to ensure the safety of the protocol using risk analysis methods such as process mapping and failure modes and effects analysis. In addition, safety of the in-house software required to implement the technique was managed through use cases and quantitative, testable safety requirements.

The physiological significance of the 5D model parameters was investigated, particularly their dependence on breathing rate during acquisition. It was shown that the model parameter relating tissue motion to breathing amplitude was largely invariant with breathing rate during acquisition.

A prospective scanning method was developed to reduce the number of fast helical scans, and associated imaging dose, necessary to perform 5DCT while maintaining motion modeling accuracy. A simulation study was conducted using patient breathing traces, and the results demonstrated that adequate sampling of the respiratory cycle could be achieved using six scans, compared to the previously published protocol that employs twenty-five.

    Cover page: Development, validation, and translation of a respiratory motion model-based 4DCT technique for use as a clinical protocol for radiation therapy treatment planning
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2015)

    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.
      Cover page: A Method for Assessing Ground-Truth Accuracy of the 5DCT Technique
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2019)

      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.
        Cover page: Feasibility of deriving a novel imaging biomarker based on patient-specific lung elasticity for characterizing the degree of COPD in lung SBRT patients
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2018)

        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.
          Cover page: Model-Interpolated Gating for Magnetic Resonance Image–Guided Radiation Therapy
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2015)

          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.
            Cover page: Technical Note: Simulation of 4DCT tumor motion measurement errors
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2018)

            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.
              Cover page: Investigating the minimum scan parameters required to generate free-breathing motion artefact-free fast-helical CT
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2017)

              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.
                Cover page: Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2018)
                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.
                  Cover page: Initial clinical observations of intra- and interfractional motion variation in MR-guided lung SBRT.
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2020)
                  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.
                    Cover page: Practical Safety Considerations for Integration of Magnetic Resonance Imaging in Radiation Therapy
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2023)

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