Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation

While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation. Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow. A 36×43×2 cm3 phantom with 255 known landmarks (~1 mm3) was scanned using 1.0T high-field open MR-SIM at isocenter in the transverse, sagittal, and coronal axes, and a 465x350x168mm 3D phantom was scanned by stepping in the superior-inferior direction in 3 overlapping positions to achieve a total 465x350x400mm sampled FOV yielding \u3e13,800 landmarks(3D Gradient-Echo, TE/TR/α = 5.54 ms/30 ms/28°, voxel size =1×1×2mm3). A binary template (reference) was generated from a phantom schematic. An automated program converted MR images to binary via masking, thresholding, and testing for connectivity to identify landmarks. Distortion maps were generated by centroid mapping. Images were corrected via warping with inverse distortion maps, and temporal stability was assessed. To determine candidate materials for phantom and software development, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3DSlicer application platform. To evaluate the performance of synthetic CTs in an image guided workflow, magnetic resonance simulation and CT simulation images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. Over the sampled FOV, non-negligible residual gradient distortions existed as close as 9.5 cm from isocenter, with a maximum distortion of 7.4mm as close as 23 cm from isocenter. Over 6 months, average gradient distortions were -0.07±1.10 mm and 0.10±1.10 mm in the x and y-directions for the transverse plane, 0.03±0.64 and -0.09±0.70 mm in the sagittal plane, and 0.4±1.16 and 0.04±0.40 mm in the coronal plane. After implementing 3D correction maps, distortions were reduced to \u3c 1 pixel width (1mm) for all voxels up to 25 cm from magnet isocenter. All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000psi, density ~20lb/ft3) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55×55×37.5 cm3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate \u3e70 cm wide bores, an extended build used 20 plates spanning 55×55×50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3DSlicer’s plugin framework and results agreed with the literature. Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4±0.5 mm (range, 0.6 to 1.6 mm), 0.0±0.5 mm (range, 0.9 to 1.2 mm), and 0.1±0.3 mm (range, 0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6±0.4 mm (range, 0.2 to 1.6 mm), 0.2±0.4 mm (range, 0.3 to 1.2 mm), and 0.2±0.3 mm (range, 0.2 to 1.2 mm) for the S-I, L-R, and A-P axes, respectively. The CT-SIM and synCT derived margins were \u3c0.3mm different. This work has characterized the inaccuracies related to GNL distortion for a previously uncharacterized MR-SIM system at large FOVs, and established that while distortions are still non-negligible after current vendor corrections are applied, simple post-processing methods can be used to further reduce these distortions to less than 1mm for the entire field of view. Additionally, it was important to not only establish effective corrections, but to establish the previously uncharacterized temporal stability of these corrections. This work also developed methods to improve the accessibility of these distortion characterizations and corrections. We first tested the application of a more readily available 2D phantom as a surrogate for 3D distortion characterization by stepping the table with an integrated batch script file. Later we developed and constructed a large modular distortion phantom using easily obtainable materials, and showed and constructed a large modular distortion phantom using easily obtainable materials, and used it to characterize the distortion on several widely available MR systems. To accompany this phantom, open source software was also developed for easy characterization of system-dependent distortions. Finally, while the dosimetric equivalence of synCT with CT has been well established, it was necessary to characterize any differences that may exist between synCT and CT in an IGRT setting. This work has helped to establish the geometric equivalence of these two modalities, with some caveats that have been discussed at length

ORGAN MOTION AND IMAGE GUIDANCE IN RADIATION THERAPY

Organ motion and inaccurate patient positioning may compromise radiation therapy outcome. With the aid of image guidance, it is possible to allow for a more accurate organ motion and motion control study, which could lead to the reduction of irradiated healthy tissues and possible dose escalation to the target volume to achieve better treatment results. The studies on the organ motion and image guidance were divided into the following four sections. The first, the interfractional setup uncertainties from day-to-day treatment and intrafractional internal organ motion within the daily treatment from five different anatomic sites were studied with Helical TomoTherapy unit. The pre-treatment mega voltage computed tomography (MVCT) provided the real-time tumor and organ shift coordinates, and can be used to improve the accuracy of patient positioning. The interfractional system errors and random errors were analyzed and the suggested margins for HN, brain, prostate, abdomen and lung were derived. The second, lung stereotactic body radiation therapy using the MIDCO BodyLoc whole body stereotactic localizer combined with TomoTherapy MVCT image guidance were investigated for the possible target and organ motion reduction. The comparison of 3D displacement with and without BodyLoc immobilization showed that, suppression of internal organ motion was improved by using BodyLoc in this study. The third, respiration related tumor motion was accurately studied with the four dimensional computed tomography (4DCT). Deformable registration between different breathing phases was performed to estimate the motion trajectory for lung tumor. Optimization is performed by minimizing the mean squared difference in intensity, and is implemented with a multi-resolution, gradient descent procedure. The fourth, lung tumor mobility and dosimetric benefits were compared with different PTV obtained from 3DCT and 4DCT. The results illustrated that the PTV3D not only included excess normal tissues but also might result in missed target tissue. The normal tissue complication probability (NTCP) from 4D plan was statistically significant smaller than 3D plan for both ipsilateral lung and heart

Development of a Novel Technique for Predicting Tumor Response in Adaptive Radiation Therapy

This dissertation concentrates on the introduction of Predictive Adaptive Radiation Therapy (PART) as a potential method to improve cancer treatment. PART is a novel technique that utilizes volumetric image-guided radiation therapy treatment (IGRT) data to actively predict the tumor response to therapy and estimate clinical outcomes during the course of treatment. To implement PART, a patient database containing IGRT image data for 40 lesions obtained from patients who were imaged and treated with helical tomotherapy was constructed. The data was then modeled using locally weighted regression. This model predicts future tumor volumes and masses and the associated confidence intervals based on limited observations during the first two weeks of treatment. All predictions were made using only 8 days worth of observations from early in the treatment and were all bound by a 95% confidence interval. Since the predictions were accurate with quantified uncertainty, they could eventually be used to optimize and adapt treatment accordingly, hence the term PART (Predictive Adaptive Radiation Therapy). A challenge in implementing PART in a clinical setting is the increased quality assurance that it will demand. To help ease this burden, a technique was developed to automatically evaluate helical tomotherapy treatments during delivery using exit detector data. This technique uses an auto-associative kernel regression (AAKR) model to detect errors in tomotherapy delivery. This modeling scheme is especially suited for the problem of monitoring the fluence values found in the exit detector data because it is able to learn the complex detector data relationships. Several AAKR models were tested using tomotherapy detector data from deliveries that had intentionally inserted errors and different attenuations from the sinograms that were used to develop the model. The model proved to be robust and could predict the correct “error-free” values for a projection in which the opening time of a single MLC leaf had been decreased by 10%. The model also was able to determine machine output errors. The automation of this technique should significantly ease the QA burden that accompanies adaptive therapy, and will help to make the implementation of PART more feasible

Simulation-Based Joint Estimation of Body Deformation and Elasticity Parameters for Medical Image Analysis

Elasticity parameter estimation is essential for generating accurate and controlled simulation results for computer animation and medical image analysis. However, finding the optimal parameters for a particular simulation often requires iterations of simulation, assessment, and adjustment and can become a tedious process. Elasticity values are especially important in medical image analysis, since cancerous tissues tend to be stiffer. Elastography is a popular type of method for finding stiffness values by reconstructing a dense displacement field from medical images taken during the application of forces or vibrations. These methods, however, are limited by the imaging modality and the force exertion or vibration actuation mechanisms, which can be complicated for deep-seated organs. In this thesis, I present a novel method for reconstructing elasticity parameters without requiring a dense displacement field or a force exertion device. The method makes use of natural deformations within the patient and relies on surface information from segmented images taken on different days. The elasticity value of the target organ and boundary forces acting on surrounding organs are optimized with an iterative optimizer, within which the deformation is always generated by a physically-based simulator. Experimental results on real patient data are presented to show the positive correlation between recovered elasticity values and clinical prostate cancer stages. Furthermore, to resolve the performance issue arising from the high dimensionality of boundary forces, I propose to use a reduced finite element model to improve the convergence of the optimizer. To find the set of bases to represent the dimensions for forces, a statistical training based on real patient data is performed. I demonstrate the trade-off between accuracy and performance by using different numbers of bases in the optimization using synthetic data. A speedup of more than an order of magnitude is observed without sacrificing too much accuracy in recovered elasticity.Doctor of Philosoph

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on

On board cone beam CT for treatment planning in image guided radiotherapy

Background: Movement of tumours between or during radiotherapy treatment fractions poses a risk to surrounding healthy tissues and potentially lowers the treatment dose to the intended area. To increase the efficacy of radiotherapy, radiation oncologists utilise image-guided radiotherapy (IGRT) to enhance the delivery of radiation to cancerous tumours. Concern about concomitant radiation doses and poor quality images have previously limited the use of such technology when developing treatment plans for adaptive radiotherapy. Recent improvements to the On-board Imager (OBI; Varian version 1.4) including expansion of the number of acquiring modes from four to six, have rejuvenated efforts to use Cone Beam Computed Tomography (CBCT) with OBI as a radiotherapy treatment planning tool. Aim: This research aimed to investigate the possibility of using the new version of the Varian On-Board CBCT imager Vl.4, for adaptive radiotherapy. This work has led to the development of a methodology on how to initiate and implement CBCT scans for - - - - - -- -. -- - -- .- -- the purpose of increasing the accuracy of radiotherapy treatments using adaptive radiotherapy. Methods: The adaptation of radiotherapy plans using CBCT scan images involved three stages. CBCT concommitant doses were determined in the first stage by measuring the dose received by three types of phantom; the RANDO anthropomorphic phantom, the computer-imaging reference system phantom (CIRS) and cylindrical water phantoms of varying diameter. Two- and three-dimensional simulations were also obtained for CBCT using EXCEL, and Monte Carlo codes (BEAMnrc and DOSXYZnrc). The manufacturer's schematic diagram of the head was used to simulate a detailed CBCT dose simulation with the effect of beam output and bow-tie filter included as dose-modifiers. Based on these dose measurements, relationships between CBCT concomitant dose and patient size were found. In addition, estimations of secondary induced cancer were modelled based on these doses. In the second stage, CBCT scan calibrations were conducted. The relationship IV Abstract between the Hounsfield Unit (HU) and electron density (ED) of CBCT scans were described mathematically for each CIRS-062A phantom configuration. Later, these CBCT HU-to-ED calibrations were benchmarked against the CT RU-to-ED relationship of GE lightspeed CT employed in treatment planning. Finally, in the third stage, the obtained HU-to-ED calibrations were applied to treatment plans calculated on CIRS and RANDO phantoms using single-beam and IMRT configurations. Dose calculations derived from the OBI CBCT were compared with those from the GE Lightspeed CT. Results:Using a female RANDO phantom, doses were lowered by factors of36, 8,22 and 16, at the eyes, oesophagus, thyroid and brain, respectively, when using the new version ofVarian CBCT vl.4. In both the standard dose head mode and pelvis mode, the concomitant dose at all positions decreases as the phantom size increases. The concomitant dose measured on the smallest cylindrical water phantoms (10cm in diameter) resulted in a theoretical risk of secondary skin cancer of 0.005% in the standard dose mode and 0.05% in the pelvis mode, assuming a 30-fraction course of ---- -treatmentwith CBCT images acquired on a daily basis. Importantly, these-doses are - approximately 10 times greater than those measured for the largest phantom. The risk of secondary cancer for this phantom size at the oesophagus, thyroid, and brain sites are 0.0443, 0.0106 and 0.0439 % respectively for 30 daily images of head and neck treatment. Dose calculations on both the CIRS and RANDO phantoms showed that for the single beam treatment, only 1 % difference in the mean dose values are delivered to the majority of insertions when using the original CT or CBCT images and respective calibration curves. The only exception was for dense bone, which exhibited a 2% difference. For the IMRT treatment plan results showed that when the CT scan image is used the mean doses were less than 1.1 %. Conclusion: CBCT doses from the OBI version 1.4 are significantly lower than doses from version 1.3, making it possible to use CBCT to assist with adaptive radiotherapy on a daily basis, without a significantly increased secondary cancer risk. This technology is a useful tool to aid patient positioning for radiotherapy and to allow v Abstract VI daily adaptive IGRT. Radiation dose varies significantly with both patient size and tumour position in relation to scanning mode. It is therefore recommended that patient-specific imaging protocols be considered, especially with regard to paediatric patients who can be expected to receive a higher dose. The single beam and the WRT comparisons showed that the CBCT images and calibration curves can be used in treatment planning.EThOS - Electronic Theses Online ServiceGBUnited Kingdo