Multi-modal deformable medical image registration

Non-rigid image registration is an essential tool required for overcoming the inherent local anatomical variations that exist between images acquired from different individuals or atlases. Furthermore, certain applications require this type of registration to operate across images acquired from different imaging modalities. One popular local approach for estimating this registration is a block matching procedure utilising the mutual information criterion. However, previous block matching procedures generate a sparse deformation field containing displacement estimates at uniformly spaced locations. This neglects to make use of the evidence that block matching results are dependent on the amount of local information content. This paper presents a solution to this drawback by proposing the use of a Reversible Jump Markov Chain Monte Carlo statistical procedure to optimally select grid points of interest. Three different methods are then compared to propagate the estimated sparse deformation field to the entire image including a thin-plate spline warp, Gaussian convolution, and a hybrid fluid technique. Results show that non-rigid registration can be improved by using the proposed algorithm to optimally select grid points of interest.

Boosting the margin: A new explanation for the effectiveness of voting methods

One of the surprising recurring phenomena observed in experiments with boosting is that the test error of the generated classifier usually does not increase as its size becomes very large, and often is observed to decrease even after the training error reaches zero. In this paper, we show that this phenomenon is related to the distribution of margins of the training examples with respect to the generated voting classification rule, where the margin of an example is simply the difference between the number of correct votes and the maximum number of votes received by any incorrect label. We show that techniques used in the analysis of Vapnik's support vector classifiers and of neural networks with small weights can be applied to voting methods to relate the margin distribution to the test error. We also show theoretically and experimentally that boosting is especially effective at increasing the margins of the training examples. Finally, we compare our explanation to those based on the bias-variance decomposition.

Using Bayesian methods for the estimation of uncertainty in complex statistical models

The research objectives of this thesis were to contribute to Bayesian statistical methodology by contributing to risk assessment statistical methodology, and to spatial and spatio-temporal methodology, by modelling error structures using complex hierarchical models. Specifically, I hoped to consider two applied areas, and use these applications as a springboard for developing new statistical methods as well as undertaking analyses which might give answers to particular applied questions. Thus, this thesis considers a series of models, firstly in the context of risk assessments for recycled water, and secondly in the context of water usage by crops. The research objective was to model error structures using hierarchical models in two problems, namely risk assessment analyses for wastewater, and secondly, in a four dimensional dataset, assessing differences between cropping systems over time and over three spatial dimensions. The aim was to use the simplicity and insight afforded by Bayesian networks to develop appropriate models for risk scenarios, and again to use Bayesian hierarchical models to explore the necessarily complex modelling of four dimensional agricultural data. The specific objectives of the research were to develop a method for the calculation of credible intervals for the point estimates of Bayesian networks; to develop a model structure to incorporate all the experimental uncertainty associated with various constants thereby allowing the calculation of more credible credible intervals for a risk assessment; to model a single day’s data from the agricultural dataset which satisfactorily captured the complexities of the data; to build a model for several days’ data, in order to consider how the full data might be modelled; and finally to build a model for the full four dimensional dataset and to consider the timevarying nature of the contrast of interest, having satisfactorily accounted for possible spatial and temporal autocorrelations. This work forms five papers, two of which have been published, with two submitted, and the final paper still in draft. The first two objectives were met by recasting the risk assessments as directed, acyclic graphs (DAGs). In the first case, we elicited uncertainty for the conditional probabilities needed by the Bayesian net, incorporated these into a corresponding DAG, and used Markov chain Monte Carlo (MCMC) to find credible intervals, for all the scenarios and outcomes of interest. In the second case, we incorporated the experimental data underlying the risk assessment constants into the DAG, and also treated some of that data as needing to be modelled as an ‘errors-invariables’ problem [Fuller, 1987]. This illustrated a simple method for the incorporation of experimental error into risk assessments. In considering one day of the three-dimensional agricultural data, it became clear that geostatistical models or conditional autoregressive (CAR) models over the three dimensions were not the best way to approach the data. Instead CAR models are used with neighbours only in the same depth layer. This gave flexibility to the model, allowing both the spatially structured and non-structured variances to differ at all depths. We call this model the CAR layered model. Given the experimental design, the fixed part of the model could have been modelled as a set of means by treatment and by depth, but doing so allows little insight into how the treatment effects vary with depth. Hence, a number of essentially non-parametric approaches were taken to see the effects of depth on treatment, with the model of choice incorporating an errors-in-variables approach for depth in addition to a non-parametric smooth. The statistical contribution here was the introduction of the CAR layered model, the applied contribution the analysis of moisture over depth and estimation of the contrast of interest together with its credible intervals. These models were fitted using WinBUGS [Lunn et al., 2000]. The work in the fifth paper deals with the fact that with large datasets, the use of WinBUGS becomes more problematic because of its highly correlated term by term updating. In this work, we introduce a Gibbs sampler with block updating for the CAR layered model. The Gibbs sampler was implemented by Chris Strickland using pyMCMC [Strickland, 2010]. This framework is then used to consider five days data, and we show that moisture in the soil for all the various treatments reaches levels particular to each treatment at a depth of 200 cm and thereafter stays constant, albeit with increasing variances with depth. In an analysis across three spatial dimensions and across time, there are many interactions of time and the spatial dimensions to be considered. Hence, we chose to use a daily model and to repeat the analysis at all time points, effectively creating an interaction model of time by the daily model. Such an approach allows great flexibility. However, this approach does not allow insight into the way in which the parameter of interest varies over time. Hence, a two-stage approach was also used, with estimates from the first-stage being analysed as a set of time series. We see this spatio-temporal interaction model as being a useful approach to data measured across three spatial dimensions and time, since it does not assume additivity of the random spatial or temporal effects.

Novel methods and the maximum likelihood estimation technique for estimating traffic critical gap

Most unsignalised intersection capacity calculation procedures are based on gap acceptance models. Accuracy of critical gap estimation affects accuracy of capacity and delay estimation. Several methods have been published to estimate drivers’ sample mean critical gap, the Maximum Likelihood Estimation (MLE) technique regarded as the most accurate. This study assesses three novel methods; Average Central Gap (ACG) method, Strength Weighted Central Gap method (SWCG), and Mode Central Gap method (MCG), against MLE for their fidelity in rendering true sample mean critical gaps. A Monte Carlo event based simulation model was used to draw the maximum rejected gap and accepted gap for each of a sample of 300 drivers across 32 simulation runs. Simulation mean critical gap is varied between 3s and 8s, while offered gap rate is varied between 0.05veh/s and 0.55veh/s. This study affirms that MLE provides a close to perfect fit to simulation mean critical gaps across a broad range of conditions. The MCG method also provides an almost perfect fit and has superior computational simplicity and efficiency to the MLE. The SWCG method performs robustly under high flows; however, poorly under low to moderate flows. Further research is recommended using field traffic data, under a variety of minor stream and major stream flow conditions for a variety of minor stream movement types, to compare critical gap estimates using MLE against MCG. Should the MCG method prove as robust as MLE, serious consideration should be given to its adoption to estimate critical gap parameters in guidelines.

Bayesian hierarchical models in statistical quality control methods to improve healthcare in hospitals

Quality oriented management systems and methods have become the dominant business and governance paradigm. From this perspective, satisfying customers’ expectations by supplying reliable, good quality products and services is the key factor for an organization and even government. During recent decades, Statistical Quality Control (SQC) methods have been developed as the technical core of quality management and continuous improvement philosophy and now are being applied widely to improve the quality of products and services in industrial and business sectors. Recently SQC tools, in particular quality control charts, have been used in healthcare surveillance. In some cases, these tools have been modified and developed to better suit the health sector characteristics and needs. It seems that some of the work in the healthcare area has evolved independently of the development of industrial statistical process control methods. Therefore analysing and comparing paradigms and the characteristics of quality control charts and techniques across the different sectors presents some opportunities for transferring knowledge and future development in each sectors. Meanwhile considering capabilities of Bayesian approach particularly Bayesian hierarchical models and computational techniques in which all uncertainty are expressed as a structure of probability, facilitates decision making and cost-effectiveness analyses. Therefore, this research investigates the use of quality improvement cycle in a health vii setting using clinical data from a hospital. The need of clinical data for monitoring purposes is investigated in two aspects. A framework and appropriate tools from the industrial context are proposed and applied to evaluate and improve data quality in available datasets and data flow; then a data capturing algorithm using Bayesian decision making methods is developed to determine economical sample size for statistical analyses within the quality improvement cycle. Following ensuring clinical data quality, some characteristics of control charts in the health context including the necessity of monitoring attribute data and correlated quality characteristics are considered. To this end, multivariate control charts from an industrial context are adapted to monitor radiation delivered to patients undergoing diagnostic coronary angiogram and various risk-adjusted control charts are constructed and investigated in monitoring binary outcomes of clinical interventions as well as postintervention survival time. Meanwhile, adoption of a Bayesian approach is proposed as a new framework in estimation of change point following control chart’s signal. This estimate aims to facilitate root causes efforts in quality improvement cycle since it cuts the search for the potential causes of detected changes to a tighter time-frame prior to the signal. This approach enables us to obtain highly informative estimates for change point parameters since probability distribution based results are obtained. Using Bayesian hierarchical models and Markov chain Monte Carlo computational methods, Bayesian estimators of the time and the magnitude of various change scenarios including step change, linear trend and multiple change in a Poisson process are developed and investigated. The benefits of change point investigation is revisited and promoted in monitoring hospital outcomes where the developed Bayesian estimator reports the true time of the shifts, compared to priori known causes, detected by control charts in monitoring rate of excess usage of blood products and major adverse events during and after cardiac surgery in a local hospital. The development of the Bayesian change point estimators are then followed in a healthcare surveillances for processes in which pre-intervention characteristics of patients are viii affecting the outcomes. In this setting, at first, the Bayesian estimator is extended to capture the patient mix, covariates, through risk models underlying risk-adjusted control charts. Variations of the estimator are developed to estimate the true time of step changes and linear trends in odds ratio of intensive care unit outcomes in a local hospital. Secondly, the Bayesian estimator is extended to identify the time of a shift in mean survival time after a clinical intervention which is being monitored by riskadjusted survival time control charts. In this context, the survival time after a clinical intervention is also affected by patient mix and the survival function is constructed using survival prediction model. The simulation study undertaken in each research component and obtained results highly recommend the developed Bayesian estimators as a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances as well as industrial and business contexts. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The empirical results and simulations indicate that the Bayesian estimators are a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The advantages of the Bayesian approach seen in general context of quality control may also be extended in the industrial and business domains where quality monitoring was initially developed.

Statistical methods for electromyography data and associated problems

This thesis proposes three novel models which extend the statistical methodology for motor unit number estimation, a clinical neurology technique. Motor unit number estimation is important in the treatment of degenerative muscular diseases and, potentially, spinal injury. Additionally, a recent and untested statistic to enable statistical model choice is found to be a practical alternative for larger datasets. The existing methods for dose finding in dual-agent clinical trials are found to be suitable only for designs of modest dimensions. The model choice case-study is the first of its kind containing interesting results using so-called unit information prior distributions.

Bayesian computational methods for spatial analysis of images

This thesis introduces a new way of using prior information in a spatial model and develops scalable algorithms for fitting this model to large imaging datasets. These methods are employed for image-guided radiation therapy and satellite based classification of land use and water quality. This study has utilized a pre-computation step to achieve a hundredfold improvement in the elapsed runtime for model fitting. This makes it much more feasible to apply these models to real-world problems, and enables full Bayesian inference for images with a million or more pixels.

Sampling Methods for Exploring Between Subject Variability in Cardiac Electrophysiology Experiments

Between-subject and within-subject variability is ubiquitous in biology and physiology and understanding and dealing with this is one of the biggest challenges in medicine. At the same time it is difficult to investigate this variability by experiments alone. A recent modelling and simulation approach, known as population of models (POM), allows this exploration to take place by building a mathematical model consisting of multiple parameter sets calibrated against experimental data. However, finding such sets within a high-dimensional parameter space of complex electrophysiological models is computationally challenging. By placing the POM approach within a statistical framework, we develop a novel and efficient algorithm based on sequential Monte Carlo (SMC). We compare the SMC approach with Latin hypercube sampling (LHS), a method commonly adopted in the literature for obtaining the POM, in terms of efficiency and output variability in the presence of a drug block through an in-depth investigation via the Beeler-Reuter cardiac electrophysiological model. We show improved efficiency via SMC and that it produces similar responses to LHS when making out-of-sample predictions in the presence of a simulated drug block.

Whole of life cycle cost analysis in bridge rehabilitation

The report presents a methodology for whole of life cycle cost analysis of alternative treatment options for bridge structures, which require rehabilitation. The methodology has been developed after a review of current methods and establishing that a life cycle analysis based on a probabilistic risk approach has many advantages including the essential ability to consider variability of input parameters. The input parameters for the analysis are identified as initial cost, maintenance, monitoring and repair cost, user cost and failure cost. The methodology utilizes the advanced simulation technique of Monte Carlo simulation to combine a number of probability distributions to establish the distribution of whole of life cycle cost. In performing the simulation, the need for a powerful software package, which would work with spreadsheet program, has been identified. After exploring several products on the market, @RISK software has been selected for the simulation. In conclusion, the report presents a typical decision making scenario considering two alternative treatment options.

Sensitivity analysis of voltage imbalance in distribution networks with rooftop PVs

A comprehensive voltage imbalance sensitivity analysis and stochastic evaluation based on the rating and location of single-phase grid-connected rooftop photovoltaic cells (PVs) in a residential low voltage distribution network are presented. The voltage imbalance at different locations along a feeder is investigated. In addition, the sensitivity analysis is performed for voltage imbalance in one feeder when PVs are installed in other feeders of the network. A stochastic evaluation based on Monte Carlo method is carried out to investigate the risk index of the non-standard voltage imbalance in the network in the presence of PVs. The network voltage imbalance characteristic based on different criteria of PV rating and location and network conditions is generalized. Improvement methods are proposed for voltage imbalance reduction and their efficacy is verified by comparing their risk index using Monte Carlo simulations.

Multi-objective mission flight planning in civil unmanned aerial systems

Unmanned Aerial Vehicles (UAVs) are emerging as an ideal platform for a wide range of civil applications such as disaster monitoring, atmospheric observation and outback delivery. However, the operation of UAVs is currently restricted to specially segregated regions of airspace outside of the National Airspace System (NAS). Mission Flight Planning (MFP) is an integral part of UAV operation that addresses some of the requirements (such as safety and the rules of the air) of integrating UAVs in the NAS. Automated MFP is a key enabler for a number of UAV operating scenarios as it aids in increasing the level of onboard autonomy. For example, onboard MFP is required to ensure continued conformance with the NAS integration requirements when there is an outage in the communications link. MFP is a motion planning task concerned with finding a path between a designated start waypoint and goal waypoint. This path is described with a sequence of 4 Dimensional (4D) waypoints (three spatial and one time dimension) or equivalently with a sequence of trajectory segments (or tracks). It is necessary to consider the time dimension as the UAV operates in a dynamic environment. Existing methods for generic motion planning, UAV motion planning and general vehicle motion planning cannot adequately address the requirements of MFP. The flight plan needs to optimise for multiple decision objectives including mission safety objectives, the rules of the air and mission efficiency objectives. Online (in-flight) replanning capability is needed as the UAV operates in a large, dynamic and uncertain outdoor environment. This thesis derives a multi-objective 4D search algorithm entitled Multi- Step A* (MSA*) based on the seminal A* search algorithm. MSA* is proven to find the optimal (least cost) path given a variable successor operator (which enables arbitrary track angle and track velocity resolution). Furthermore, it is shown to be of comparable complexity to multi-objective, vector neighbourhood based A* (Vector A*, an extension of A*). A variable successor operator enables the imposition of a multi-resolution lattice structure on the search space (which results in fewer search nodes). Unlike cell decomposition based methods, soundness is guaranteed with multi-resolution MSA*. MSA* is demonstrated through Monte Carlo simulations to be computationally efficient. It is shown that multi-resolution, lattice based MSA* finds paths of equivalent cost (less than 0.5% difference) to Vector A* (the benchmark) in a third of the computation time (on average). This is the first contribution of the research. The second contribution is the discovery of the additive consistency property for planning with multiple decision objectives. Additive consistency ensures that the planner is not biased (which results in a suboptimal path) by ensuring that the cost of traversing a track using one step equals that of traversing the same track using multiple steps. MSA* mitigates uncertainty through online replanning, Multi-Criteria Decision Making (MCDM) and tolerance. Each trajectory segment is modeled with a cell sequence that completely encloses the trajectory segment. The tolerance, measured as the minimum distance between the track and cell boundaries, is the third major contribution. Even though MSA* is demonstrated for UAV MFP, it is extensible to other 4D vehicle motion planning applications. Finally, the research proposes a self-scheduling replanning architecture for MFP. This architecture replicates the decision strategies of human experts to meet the time constraints of online replanning. Based on a feedback loop, the proposed architecture switches between fast, near-optimal planning and optimal planning to minimise the need for hold manoeuvres. The derived MFP framework is original and shown, through extensive verification and validation, to satisfy the requirements of UAV MFP. As MFP is an enabling factor for operation of UAVs in the NAS, the presented work is both original and significant.

Technical note : modelling a complex micro-multileaf collimator using the standard BEAMnrc distribution

Purpose: The component modules in the standard BEAMnrc distribution may appear to be insufficient to model micro-multileaf collimators that have tri-faceted leaf ends and complex leaf profiles. This note indicates, however, that accurate Monte Carlo simulations of radiotherapy beams defined by a complex collimation device can be completed using BEAMnrc's standard VARMLC component module.---------- Methods: That this simple collimator model can produce spatially and dosimetrically accurate micro-collimated fields is illustrated using comparisons with ion chamber and film measurements of the dose deposited by square and irregular fields incident on planar, homogeneous water phantoms.---------- Results: Monte Carlo dose calculations for on- and off-axis fields are shown to produce good agreement with experimental values, even upon close examination of the penumbrae.--------- Conclusions: The use of a VARMLC model of the micro-multileaf collimator, along with a commissioned model of the associated linear accelerator, is therefore recommended as an alternative to the development or use of in-house or third-party component modules for simulating stereotactic radiotherapy and radiosurgery treatments. Simulation parameters for the VARMLC model are provided which should allow other researchers to adapt and use this model to study clinical stereotactic radiotherapy treatments.