Deformation Estimation and Assessment of Its Accuracy in Ultrasound Images

This thesis aims to address two problems; one in ultrasound elastography and one in image registration. The first problem entails estimation of tissue displacement in Ultrasound Elastography (UE). UE is an emerging technique used to estimate mechanical properties of tissue. It involves calculating the displacement field between two ultrasound Radio Frequency (RF) frames taken before and after a tissue deformation. A common way to calculate the displacement is to use correlation based approaches. However, these approaches fail in the presence of signal decorrelation. To address this issue, Dynamic Programming was used to find the optimum displacement using all the information on the RF-line. Although taking this approach improved the results, some failures persisted. In this thesis, we have formulated the DP method on a tree. Doing so allows for more information to be used for estimating the displacement and therefore reducing the error. We evaluated our method on simulation, phantom and real patient data. Our results shows that the proposed method outperforms the previous method in terms of accuracy with small added computational cost. In this work, we also address a problem in image registration. Although there is a vast literature in image registration, quality evaluation of registration is a field that has not received as much attention. This evaluation becomes even more crucial in medical imaging due to the sensitive nature of the field. We have addressed the said problem in the context of ultrasound guided radiotherapy. Image guidance has become an important part of radiotherapy wherein image registration is a critical step. Therefore, an evaluation of this registration can play an important role in the outcome of the therapy. In this work, we propose using both bootstrapping and supervised learning methods to evaluate the registration. We test our methods on 2D and 3D data acquired from phantom and patients. According to our results, both methods perform well while having advantages and disadvantages over one another. Supervised learning methods offer more accuracy and less computation time. On the other hand, for bootstrapping, no training data is required and also offers more sensitivity

4D-treatment with patches and rescanning in proton therapy

The aim of this study, carried out at the Center for Proton Therapy of the Paul Scherrer Institute (Villigen, Switzerland), involves the verification of the possibility of 4D treatments on patients requesting a patch field. This technique is used when the dimensions of the area to be irradiated are greater than 12 cm for the T direction and 20 cm for the U direction. We also went to research the setup that provides a better dose homogeneity, in order to mitigate the tumor's motion during the treatment. Three clinical cases were studied with the motions obtained from the respective 4DCT. Moreover, one of these was analyzed again simulating a motion extrapolated from a 4D-MRI. All 4 cases were analyzed in 9 combinations, 3 possible rescan scenarios (1, 4 and 8 rescan) and 3 different overlapping setups between the two patches (0, 1 and 2 cm of overlap). The values obtained were compared to the 3D plan. The dose homogeneity measures (D5-D95 and V95) showed that in the case of a slight motion (under 2 mm) there was no need to intervene with motion mitigation. For the motions classified of medium intensity (2-10 mm), it was found the need to introduce motion mitigation. In none of the previous cases, a systematic benefit emerged with a certain pattern of patch overlap. It was not possible to fully evaluate the last case, having a large motion (about 20 mm), as it needed an IMPT plan (technique not yet developed for the 4D), but still indications, regarding the benefit of the use of 8 rescan and greater possible overlap, emerged. The experimental measurements obtained at Gantry 2 with the use of a 2D detector (Octavius 1500 XDR), a gating system and a Quasar motion platform, confirmed that there are no problems with the actual dose release. The homogeneity of the dose is also found when there are extreme conditions, such as 2 cm overlap, 8 rescan and 4 patches (for a 4 cm zone receiving 32 rescan) and a strong simulated motion

A Rapid Dosimetric Assessment Method Using Cone Beam CT in Prostate Cancer Patients

Objective: Cone beam CT (CBCT) images contain more scatter than a conventional CT image and therefore provide inaccurate Hounsfield units (HU). Consequently CBCT images cannot be used directly for radiotherapy dose calculation. The aim of this study is to enable dose calculations to be performed with the use of CBCT images taken during radiotherapy and evaluate the necessity of re-planning. Methods: A phantom, a standard prostate cancer patient and prostate cancer patients with single and double metallic hips were imaged using both CT and CBCT. A multilevel threshold algorithm (MLT) was used to categorise pixel values in the CBCT images into segments of homogeneous HU. The variation in HU with position in the CBCT images was taken into consideration and the benefit of using a large number of materials has been explored. This segmentation method relies upon the operator dividing the CBCT data into a set of volumes where the variation in the relationship between pixel values and HUs is small. In addition, an automated MLT algorithm was developed to reduce the operator time associated with the process. Furthermore, magnetic resonance (MR) images of the standard prostate case were segmented and converted into HUs using the MLT algorithm. Radiotherapy treatment plans were generated from CT images and then copied to the segmented CBCT and MR data sets and the doses were recalculated and compared using pencil beam (PB), collapsed cone (CC) and Monte Carlo (MC) algorithms. Results: Compared with the planning CT (pCT) treatment plan, in the phantom case, a gamma evaluation showed all points in planning target volume (PTV), rectum and bladder had gamma value < 1 (3%/3 mm) in the segmented CBCT, when considering only 2 material bins, water and bone. For the standard patient case, using 3 materials, air, water and bone, was accurate enough to provide accurate dose calculations with differences of less than 2%. For the patient with a metallic hip, increasing the number of bins to define the material type from 7 materials to 8 materials, required 50% more operator time to improve the accuracy by 0.01% using PB and CC and 0.05% when using MC algorithms. The use of 5 values of HU (air, adipose, water, bone and metal implant) gave the best balance between dose accuracy and operator time (3.5 hours). For the patient with double hip prosthetics, segmenting CBCT into 5 materials with the MLT algorithm showed –0.46% dose difference with 8 hours operator time, whilst the automated MLT algorithm showed –1.36%. For the standard case, the segmentation of MR images, into 3 materials, resulted in a dose difference of –1.31% with 2 hours operator time. Conclusion: The segmentation of CBCT images using the method in this study can be used for dose calculation. For a simple phantom and standard prostate case, 2 and 3 values of HU were needed to improve dose calculation accuracy, respectively. For patients with additional anatomical inhomogeneities such as metallic hips, 5 values of HU were found to be needed, giving a reasonable balance between dose accuracy and operator time. The automated MLT algorithm reduced the operator time associated with implementing the MLT algorithm to achieve clinically acceptable accuracy. This saved time makes the automated MLT algorithm superior and easier to implement in the clinical setting. The MLT method can be applicable for the dose calculation on MR images and can be of interest to MRI-only based radiotherapy treatment planning

Modelling and verification of doses delivered to deformable moving targets in radiotherapy

During the last two decades, advanced treatment techniques have been developed in radiotherapy to achieve more conformal beam targeting of cancerous lesions. The advent of these techniques, such as intensity modulated radiotherapy (IMRT), volumetric modulated arc radiothreapy (VMAT), Tomotherapy etc., allows more precise localisation of higher doses to complex-shaped target volumes, thereby sparing more healthy tissue. In this context, motion management is a critical issue in contemporary radiotherapy (RT). That anatomic structures move during respiration is well known and much research is presently being devoted to strategies to contend with organ motion. However, moving structures are typically regarded as rigid bodies. The fact that many structures deform as a result of motion makes their resultant dose distributions difficult to measure and calculate, and has not been fully accounted for. The potential for ineffective treatments that do not take into account motion and anatomic deformation is self-evident. This thesis addresses the pressing need to investigate dose distributions in targets that deform during and/or between treatments, to ensure robust calculations for dose accumulation and delivery, thus providing the most positive outcomes for patients. This involves the direct measurement of complex and re-distributed dose in deforming objects (an experimental model), as well as calculations of the deformed dose distribution (a mathematical model). The comparison thereof aims to validate the dose deformation technique, thereby to apply the method to a clinical example such as liver stereotactic body radiotherapy. To facilitate four-dimensional deformable dosimetry for both external beam radiotherapy and brachytherapy, methodologies for three-dimensional deformed dose measurements were developed and employed using radiosensitive polymer gel combined with a cone beam optical computed tomography (CT) scanner. This includes the development of a novel prototype deformable target volume using a tissue-equivalent, deformable gel dosimetric phantom, dubbed &amp;ldquo;defgel&amp;rdquo;. This can reproducibly simulate targets subject to a range of mass- and density-conserving deformations representative of those observable in anatomical targets. This novel tool was characterised in terms of its suitability for the measurement of dose in deforming geometries. It was demonstrated that planned doses could be delivered to the deformable gel dosimeter in the presence of different deformations and complex spatial re-distributions of dose in all three dimensions could be quantified. For estimating the cumulative dose in different deformed states, deformable image registration (DIR) algorithms were implemented to &amp;lsquo;morph&amp;rsquo; a dose distribution calculated by a treatment planning system. To investigate the performance of DIR and dose-warping technique, two key studies were undertaken. The first was to systematically assess the accuracy of a range of different DIR algorithms available in the public domain and quantitatively examine, in particular, low-contrast regions, where accuracy had not previously been established. This work investigates DIR algorithms in 3D via a systematic evaluation process using defgel suitable for verification of mass- and density-conserving deformations. The second study was a full three-dimensional experimental validation of the dose-warping technique using the evaluated DIR algorithm and comparing it to directly measured deformed dose distributions from defgel. It was shown that the dose-warping can be accurate, i.e. over 95% passing rate of 3D-gamma analysis with 3%/3mm criteria for given extents of deformation up to 20 mm For the application of evaluating patient treatment planning involving tumour motion/deformation, two key studies were undertaken in the context of liver stereotactic body radiotherapy. The first was a 4D evaluation of conventional 3D treatment planning, combined with 4D computed tomography, in order to investigate the extent of dosimetric differences between conventional 3D-static and path-integrated 4D-cumulative dose calculation. This study showed that the 3D planning approach overestimated doses to targets by &amp;le; 9% and underestimated dose to normal liver by &amp;le; 8%, compared to the 4D methodology. The second study was to assess a consequent reduction of healthy tissue sparing, which may increase risk for surrounding healthy tissues. Estimates for normal tissue complications probabilities (NTCP) based on the two dose calculation schemes are provided. While all NTCP were low for the employed fractionation scheme, analysis of common alternative schemes suggests potentially larger uncertainties exist in the estimation of NTCP for healthy liver and that substantial differences in these values may exist across the different fractionation schemes. These bodies of work have shown the potential to quantify such issues of under- and/or over-dosages which are quite patient dependent in RT. Studies presented in this work consolidate gel dosimetry, image guidance, DIR, dose-warping and consequent dose accumulation calculation to investigate the dosimetric impact and make more accurate evaluation of conventional 3D treatment plans. While liver stereotactic body radiotherapy (SBRT) was primarily concerned for immediate clinical application, the findings of this thesis are also applicable to other organs with various RT techniques. Most importantly, however, it is hoped that the outcomes of this thesis will help to improve treatment plan accuracy. By considering both computation and measurement, it is also hoped that this work will open new windows for future work and hence provide building blocks to further enhance the benefit of radiotherapy treatment

Transit dosimetry based on water equivalent path length measured with an amorphous silicon electronic portal imaging device

Abstract: Background and purpose: In vivo dosimetry is one of the quality assurance tools used in radiotherapy to monitor the dose delivered to the patient. The digital image format makes electronic portal imaging devices (EPIDs) good candidates for in vivo dosimetry. Currently there is no commercial transit dosimetry module, which could facilitate routine in vivo dosimetry with the EPID. Some centres are developing their in-house packages, and they are under assessment before introduction into routine clinical usage. The main purpose of this work was to develop the EPID as an in vivo dosimetry device. Materials and methods: Knowledge of a detector’s dose-response behaviour is a prerequisite for any clinical dosimetric application, hence in the first phase of the study, the dosimetric characteristics of eleven Varian a-Si500 EPIDs that are in clinical use in our centre were investigated. The devices have been in use for varying periods and interfaced with two different acquisition control software packages, IAS2 / IDU-II or IAS3 / IDU-20. Properties investigated include: linearity, reproducibility, signal uniformity, field size and dose-rate dependence, memory effects and image profiles as a function of dose. In the second phase, an EPID was calibrated using the quadratic method to yield values for the entrance and exit doses at the phantom or patient. EPID images for a set of solid water phantoms of varying thicknesses were acquired and the data fitted onto a quadratic equation, which relates the reduction in photon beam intensity to the attenuation coefficient and material thickness at a reference condition. The quadratic model was used to convert the measured grey scale value into water equivalent path length (EPL) at each pixel for any material imaged by the detector. For any other non-reference conditions, scatter, field size and MU variation effects on the image were corrected. The 2D EPL is linked to the percentage exit-dose for different thicknesses and field sizes, thereby converting the plane pixel values at each point into a 2D dose map at the exit surface of the imaged material. The off axis ratio is corrected using envelope and boundary profiles generated from the treatment planning system (TPS). The method was extended to include conformal and enhanced dynamic wedge (EDW) fields. A method was devised for the automatic calculation of areas (to establish the appropriate scatter correction) from the EPID image that facilitated the calculation of EPL for any field, and hence exit dose. For EDW fields, the fitting coefficients were modified by utilizing the Linac manufacturer’s golden segmented treatment tables (STT) methodology. Cross plane profiles and 2D dose distributions of EPID predicted doses were compared with those calculated with the Eclipse 8.6 treatment planning system (TPS) and those measured directly with a MapCHECK 2 device. Results: The image acquisition system influenced the dosimetric characteristics with the newer version (IAS3 with IDU-20) giving better data reproducibility and linearity fit than the older version (IAS2 with IDU-II). The irradiated field areas can be accurately determined from EPID images to within ± 1% uncertainty. The EPID predicted dose maps were compared with calculated doses from TPS at the exit. The gamma index at 3% dose difference (DD) and 3mm distance to agreement (DTA) resulted in an average of 97% acceptance for the square fields of 5, 10, 15 and 20 cm thickness solid water homogeneous phantoms. More than 90% of all points passed the gamma index acceptance criteria of 3% DD and 3mm DTA, for both conformal and EDW study cases. Comparison of the 2D EPID dose maps to those from TPS and MapCHECK shows that, more than 90% of all points passed the gamma index acceptance criteria of 3% dose difference and 3mm distance to agreement, for both conformal and EDW study cases. Conclusions: The quadratic calibration can effectively predict EPL and hence exit dose. Good agreement between the EPID predicted and TPS calculated dose distributions were obtained for open fields, conformal and EDW test cases. There were noteworthy deviations between EPID, TPS and MapCHECK doses on field edges. But it should be emphasised that, for practical in vivo dosimetry, these areas of reduced accuracy at the field edges are much less important. It is concluded that the EPID Quadratic Calibration Method (QCM) is an accurate and convenient method for online in vivo dosimetry and may therefore replace existing techniques

Analysis of first pass myocardial perfusion imaging with magnetic resonance

Early diagnosis and localisation of myocardial perfusion defects is an important step in the treatment of coronary artery disease. Thus far, coronary angiography is the conventional standard investigation for patients with known or suspected coronary artery disease and it provides information about the presence and location of coronary stenoses. In recent years, the development of myocardial perfusion CMR has extended the role of MR in the evaluation of ischaemic heart disease beyond the situations where there have already been gross myocardial changes such as acute infarction or scarring. The ability to non-invasively evaluate cardiac perfusion abnormalities before pathologic effects occur, or as follow-up to therapy, is important to the management of patients with coronary artery disease. Whilst limited multi-slice 2D CMR perfusion studies are gaining increased clinical usage for quantifying gross ischaemic burden, research is now directed towards complete 3D coverage of the myocardium for accurate localisation of the extent of possible defects. In 3D myocardial perfusion imaging, a complete volumetric data set has to be acquired for each cardiac cycle in order to study the first pass of the contrast bolus. This normally requires a relatively large acquisition window within each cardiac cycle to ensure a comprehensive coverage of the myocardium and reasonably high resolution of the images. With multi-slice imaging, long axis cardiac motion during this large acquisition window can cause the myocardium imaged in different cross- sections to be mis-registered, i.e., some part of the myocardium may be imaged more than twice whereas other parts may be missed out completely. This type of mis-registration is difficult to correct for by using post-processing techniques. The purpose of this thesis is to investigate techniques for tracking through plane motion during 3D myocardial perfusion imaging, and a novel technique for extracting intrinsic relationships between 3D cardiac deformation due to respiration and multiple ID real-time measurable surface intensity traces is developed. Despite the fact that these surface intensity traces can be strongly coupled with each other but poorly correlated with respiratory induced cardiac deformation, we demonstrate how they can be used to accurately predict cardiac motion through the extraction of latent variables of both the input and output of the model. The proposed method allows cross-modality reconstruction of patient specific models for dense motion field prediction, which after initial modelling can be use in real-time prospective motion tracking or correction. In CMR, new imaging sequences have significantly reduced the acquisition window whilst maintaining the desired spatial resolution. Further improvements in perfusion imaging will require the application of parallel imaging techniques or making full use of the information content of the ¿-space data. With this thesis, we have proposed RR-UNFOLD and RR-RIGR for significantly reducing the amount of data that is required to reconstruct the perfusion image series. The methods use prospective diaphragmatic navigator echoes to ensure UNFOLD and RIGR are carried out on a series of images that are spatially registered. An adaptive real-time re-binning algorithm is developed for the creation of static image sub-series related to different levels of respiratory motion. Issues concerning temporal smoothing of tracer kinetic signals and residual motion artefact are discussed, and we have provided a critical comparison of the relative merit and potential pitfalls of the two techniques. In addition to the technical and theoretical descriptions of the new methods developed, we have also provided in this thesis a detailed literature review of the current state-of-the-art in myocardial perfusion imaging and some of the key technical challenges involved. Issues concerning the basic background of myocardial ischaemia and its functional significance are discussed. Practical solutions to motion tracking during imaging, predictive motion modelling, tracer kinetic modelling, RR-UNFOLD and RR-RIGR are discussed, all with validation using patient and normal subject data to demonstrate both the strength and potential clinical value of the proposed techniques.Open acces

Dosimetric impact of organ motion with 4D-CT based treatment planning in lung stereotactic ablative radiotherapy

Stereotactic ablative radiotherapy (SABR) plays a major role in the treatment of lung cancer. Advances in external beam radiotherapy, such as three-dimensional conformal radiotherapy (3D CRT), intensity modulated radiation Therapy (IMRT) and volumetric modulated arc therapy (VMAT) tightly conform dose to the target volume, in turn reducing dose to the surrounding critical structures. Organ motion and setup error are two important parameters that have significant effects on the final treatment outcome in lung SABR. The effect of organ motion has a greater effect on the dose to the tumour volume that is prone to movement due to respiration. Lung cancer is one such site where the position of the tumour volume is significantly affected with respiration. Several methods have been proposed to combat tumour movement in lung cancer radiotherapy. The most common and widely followed method is to define a Maximum Intensity Projection (MIP) based tumour volume obtained from a series of CT images scanned at regular respiratory phases. The MIP based target volume encompasses the movement of tumour volume during four dimensional computed tomography (4D-CT) imaging and a treatment plan is generated based on this volume. One of drawbacks with this methodology is the inclusion of normal tissues as part of the target volume. The volume of normal tissue included as part of the MIP volume increases with increase in tumour volume movement. The MIP based volume includes low density areas but it is treated as an Internal Target Volume (ITV) and the calculation is based on Average Intensity Projection (AIP) images. Besides the organ motion challenge in treating the lung SABR, dose calculation is compromised due to the presence of low-density lung tissues surrounding the thoracic tumours [1, 2]. Lower lung densities give rise to higher doses inside the lung, and hence there is a possibility of under-dosage in the periphery of the tumour when using small fields and high-energy beams [1, 2]. The use of small-beam field sizes in the SABR technique with the presence of low density in the lung tissue can lead to exacerbating the charged particle disequilibrium (CPD) condition, where the electrons increase significantly [1, 2]. The three main aims of this thesis are as follows: The first aim: Quantify the dosimetric impact of organ motion during the treatment of lung SABR utilising an in-house custom-designed thorax dynamic phantom with the PRESAGE 3D dosimeters. This thesis also explores the dosimetric differences between the MIP based planning (conventional method) and the phase specific planning methods. The second aim: Investigate the accuracy of different dose calculation algorithms in SABR of lung using phantoms and retrospective clinical lung cases. This thesis includes a study on the dosimetric variation among three SABR techniques: 3D CRT, IMRT and VMAT using most common dose calculation algorithms anisotropic analytic algorithms (AAA) and Acuros XB. The third aim: Introduce a method for patient-specific quality assurance (QA) for SABR treatment plans as a means to replace the traditional film dosimetry. These studies will be of great values to the radiation therapy centres by improving the simulation/imaging, treatment planning, delivery planning and patient specific QA in SABR of lung

On the characterisation of stereotactic radiotherapy fields

Cancer is one of the leading causes of deaths in Australia, with a mortality rate of approximately 40,000 deaths per year, contributing $3.8 billion AUD in direct health system costs. One advanced treatment modality for small tumours is stereotactic radiotherapy, which employs multiple beams of ionising radiation that spatially conform to a targeted lesion, using higher radiation doses in fewer fractions compared to other methods. This is increasingly popular because of patient convenience and an expectation of higher cure rates. This work investigates and characterises stereotactic radiotherapy fields with the objective of improved treatments and hence better patient outcomes. Calculation and measurement of in-field characteristics is complicated by issues such as electronic disequilibrium, spectral changes and detector volume averaging effects (when the detector is of comparable or larger size than the radiation field). In this work, 3D dosimetric methods based on radiosensitive gels are developed and implemented for dose measurement, and sophisticated mathematical Monte Carlo radiation transport models are constructed and applied for accurate beam characterisation. Out-of-field doses (i.e. beyond the targeted region) are of interest for the potential health complications they may give rise to, such as radiocarcinogenesis, cardiac and respiratory problems. Comparatively little attention is given to out-of-field doses from stereotactic fields, which this study investigates both systematically and in the context of paediatric radiotherapy, providing risk estimates for radiation-induced cancer. Key findings relate to the radiological properties and calibration of 3D gel dosimeters. Monte Carlo models reveal the spectral characteristics of stereotactic fields within and beyond the nominal treatment field, and these are investigated in terms of the effect on energy-dependent dosimeters. Investigations of out-of-field dose have revealed anisotropies in the radiation field far from the primary beam which may be exploited so as to significantly minimise patient dose and corresponding health risks. The present work has yielded 11 publications in international peer-reviewed journals, a further 3 publications currently under review or preparation, 19 conference papers and 7 invited seminars