Iterative reconstruction as a novel method of radiation dose reduction at computed tomography in patients with Crohn's disease

Prior work of our research group, that quantified the alarming levels of radiation dose to patients with Crohn’s disease from medical imaging and the notable shift towards CT imaging making these patients an at risk group, provided context for this work. CT delivers some of the highest doses of ionising radiation in diagnostic radiology. Once a medical imaging examination is deemed justified, there is an onus on the imaging team to endeavour to produce diagnostic quality CT images at the lowest possible radiation dose to that patient. The fundamental limitation with conventional CT raw data reconstruction was the inherent coupling of administered radiation dose with observed image noise – the lower the radiation dose, the noisier the image. The renaissance, rediscovery and refinement of iterative reconstruction removes this limitation allowing either an improvement in image quality without increasing radiation dose or maintenance of image quality at a lower radiation dose compared with traditional image reconstruction. This thesis is fundamentally an exercise in optimisation in clinical CT practice with the objectives of assessment of iterative reconstruction as a method for improvement of image quality in CT, exploration of the associated potential for radiation dose reduction, and development of a new split dose CT protocol with the aim of achieving and validating diagnostic quality submillisiever t CT imaging in patients with Crohn’s disease. In this study, we investigated the interplay of user-selected parameters on radiation dose and image quality in phantoms and cadavers, comparing traditional filtered back projection (FBP) with iterative reconstruction algorithms. This resulted in the development of an optimised, refined and appropriate split dose protocol for CT of the abdomen and pelvis in clinical patients with Crohn’s disease allowing contemporaneous acquisition of both modified and conventional dose CT studies. This novel algorithm was then applied to 50 patients with a suspected acute complication of known Crohn’s disease and the raw data reconstructed with FBP, adaptive statistical iterative reconstruction (ASiR) and model based iterative reconstruction (MBIR). Conventional dose CT images with FBP reconstruction were used as the reference standard with which the modified dose CT images were compared in terms of radiation dose, diagnostic findings and image quality indices. As there are multiple possible user-selected strengths of ASiR available, these were compared in terms of image quality to determine the optimal strength for this modified dose CT protocol. Modified dose CT images with MBIR were also compared with contemporaneous abdominal radiograph, where performed, in terms of diagnostic yield and radiation dose. Finally, attenuation measurements in organs, tissues, etc. with each reconstruction algorithm were compared to assess for preservation of tissue characterisation capabilities. In the phantom and cadaveric models, both forms of iterative reconstruction examined (ASiR and MBIR) were superior to FBP across a wide variety of imaging protocols, with MBIR superior to ASiR in all areas other than reconstruction speed. We established that ASiR appears to work to a target percentage noise reduction whilst MBIR works to a target residual level of absolute noise in the image. Modified dose CT images reconstructed with both ASiR and MBIR were non-inferior to conventional dose CT with FBP in terms of diagnostic findings, despite reduced subjective and objective indices of image quality. Mean dose reductions of 72.9-73.5% were achieved with the modified dose protocol with a mean effective dose of 1.26mSv. MBIR was again demonstrated superior to ASiR in terms of image quality. The overall optimal ASiR strength for the modified dose protocol used in this work is ASiR 80%, as this provides the most favourable balance of peak subjective image quality indices with less objective image noise than the corresponding conventional dose CT images reconstructed with FBP. Despite guidelines to the contrary, abdominal radiographs are still often used in the initial imaging of patients with a suspected complication of Crohn’s disease. We confirmed the superiority of modified dose CT with MBIR over abdominal radiographs at comparable doses in detection of Crohn’s disease and non-Crohn’s disease related findings. Finally, we demonstrated (in phantoms, cadavers and in vivo) that attenuation values do not change significantly across reconstruction algorithms meaning preserved tissue characterisation capabilities with iterative reconstruction. Both adaptive statistical and model based iterative reconstruction algorithms represent feasible methods of facilitating acquisition diagnostic quality CT images of the abdomen and pelvis in patients with Crohn’s disease at markedly reduced radiation doses. Our modified dose CT protocol allows dose savings of up to 73.5% compared with conventional dose CT, meaning submillisievert imaging is possible in many of these patients.

BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel.

The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients. Mutations in the BRAF gene have been identified as key drivers of melanoma cells and are found in around 50% of cutaneous melanomas. Vemurafenib (Zelboraf(®) ; Roche Molecular Systems Inc., Pleasanton, CA, U.S.A.) is the first licensed inhibitor of mutated BRAF, and offers a new first-line option for patients with unresectable or metastatic melanoma who harbour BRAF mutations. Vemurafenib was developed in conjunction with a companion diagnostic, the cobas(®) 4800 BRAF V600 Mutation Test. The purpose of this paper is to make evidence-based recommendations to facilitate the implementation of BRAF mutation testing and targeted therapy in patients with metastatic melanoma in the U.K. The recommendations are the result of a meeting of an expert panel and have been reviewed by melanoma specialists and representatives of the National Cancer Research Network Clinical Study Group on behalf of the wider melanoma community. This article is intended to be a starting point for practical advice and recommendations, which will no doubt be updated as we gain further experience in personalizing therapy for patients with melanoma.

Study of Tsunami-Induced Fluid and Debris Load on Bridges using the Material Point Method

Thesis (Ph.D.)--University of Washington, 2016-08

New developments on VCA unmixing algorithm

Hyperspectral sensors are being developed for remote sensing applications. These sensors produce huge data volumes which require faster processing and analysis tools. Vertex component analysis (VCA) has become a very useful tool to unmix hyperspectral data. It has been successfully used to determine endmembers and unmix large hyperspectral data sets without the use of any a priori knowledge of the constituent spectra. Compared with other geometric-based approaches VCA is an efficient method from the computational point of view. In this paper we introduce new developments for VCA: 1) a new signal subspace identification method (HySime) is applied to infer the signal subspace where the data set live. This step also infers the number of endmembers present in the data set; 2) after the projection of the data set onto the signal subspace, the algorithm iteratively projects the data set onto several directions orthogonal to the subspace spanned by the endmembers already determined. The new endmember signature corresponds to these extreme of the projections. The capability of VCA to unmix large hyperspectral scenes (real or simulated), with low computational complexity, is also illustrated.

Anomaly Detection in Noisy Images

Finding rare events in multidimensional data is an important detection problem that has applications in many fields, such as risk estimation in insurance industry, finance, flood prediction, medical diagnosis, quality assurance, security, or safety in transportation. The occurrence of such anomalies is so infrequent that there is usually not enough training data to learn an accurate statistical model of the anomaly class. In some cases, such events may have never been observed, so the only information that is available is a set of normal samples and an assumed pairwise similarity function. Such metric may only be known up to a certain number of unspecified parameters, which would either need to be learned from training data, or fixed by a domain expert. Sometimes, the anomalous condition may be formulated algebraically, such as a measure exceeding a predefined threshold, but nuisance variables may complicate the estimation of such a measure. Change detection methods used in time series analysis are not easily extendable to the multidimensional case, where discontinuities are not localized to a single point. On the other hand, in higher dimensions, data exhibits more complex interdependencies, and there is redundancy that could be exploited to adaptively model the normal data. In the first part of this dissertation, we review the theoretical framework for anomaly detection in images and previous anomaly detection work done in the context of crack detection and detection of anomalous components in railway tracks. In the second part, we propose new anomaly detection algorithms. The fact that curvilinear discontinuities in images are sparse with respect to the frame of shearlets, allows us to pose this anomaly detection problem as basis pursuit optimization. Therefore, we pose the problem of detecting curvilinear anomalies in noisy textured images as a blind source separation problem under sparsity constraints, and propose an iterative shrinkage algorithm to solve it. Taking advantage of the parallel nature of this algorithm, we describe how this method can be accelerated using graphical processing units (GPU). Then, we propose a new method for finding defective components on railway tracks using cameras mounted on a train. We describe how to extract features and use a combination of classifiers to solve this problem. Then, we scale anomaly detection to bigger datasets with complex interdependencies. We show that the anomaly detection problem naturally fits in the multitask learning framework. The first task consists of learning a compact representation of the good samples, while the second task consists of learning the anomaly detector. Using deep convolutional neural networks, we show that it is possible to train a deep model with a limited number of anomalous examples. In sequential detection problems, the presence of time-variant nuisance parameters affect the detection performance. In the last part of this dissertation, we present a method for adaptively estimating the threshold of sequential detectors using Extreme Value Theory on a Bayesian framework. Finally, conclusions on the results obtained are provided, followed by a discussion of possible future work.

'Exploiting problem structure in a genetic algorithm approach to a nurse rostering problem'

There is considerable interest in the use of genetic algorithms to solve problems arising in the areas of scheduling and timetabling. However, the classical genetic algorithm paradigm is not well equipped to handle the conflict between objectives and constraints that typically occurs in such problems. In order to overcome this, successful implementations frequently make use of problem specific knowledge. This paper is concerned with the development of a GA for a nurse rostering problem at a major UK hospital. The structure of the constraints is used as the basis for a co-evolutionary strategy using co-operating sub-populations. Problem specific knowledge is also used to define a system of incentives and disincentives, and a complementary mutation operator. Empirical results based on 52 weeks of live data show how these features are able to improve an unsuccessful canonical GA to the point where it is able to provide a practical solution to the problem.

Exploiting problem structure in a genetic algorithm approach to a nurse rostering problem

There is considerable interest in the use of genetic algorithms to solve problems arising in the areas of scheduling and timetabling. However, the classical genetic algorithm paradigm is not well equipped to handle the conflict between objectives and constraints that typically occurs in such problems. In order to overcome this, successful implementations frequently make use of problem specific knowledge. This paper is concerned with the development of a GA for a nurse rostering problem at a major UK hospital. The structure of the constraints is used as the basis for a co-evolutionary strategy using co-operating sub-populations. Problem specific knowledge is also used to define a system of incentives and disincentives, and a complementary mutation operator. Empirical results based on 52 weeks of live data show how these features are able to improve an unsuccessful canonical GA to the point where it is able to provide a practical solution to the problem.

'Exploiting problem structure in a genetic algorithm approach to a nurse rostering problem'

There is considerable interest in the use of genetic algorithms to solve problems arising in the areas of scheduling and timetabling. However, the classical genetic algorithm paradigm is not well equipped to handle the conflict between objectives and constraints that typically occurs in such problems. In order to overcome this, successful implementations frequently make use of problem specific knowledge. This paper is concerned with the development of a GA for a nurse rostering problem at a major UK hospital. The structure of the constraints is used as the basis for a co-evolutionary strategy using co-operating sub-populations. Problem specific knowledge is also used to define a system of incentives and disincentives, and a complementary mutation operator. Empirical results based on 52 weeks of live data show how these features are able to improve an unsuccessful canonical GA to the point where it is able to provide a practical solution to the problem.

Positron Emission Tomography (PET) Tumor Segmentation and Quantification: Development of New Algorithms

Tumor functional volume (FV) and its mean activity concentration (mAC) are the quantities derived from positron emission tomography (PET). These quantities are used for estimating radiation dose for a therapy, evaluating the progression of a disease and also use it as a prognostic indicator for predicting outcome. PET images have low resolution, high noise and affected by partial volume effect (PVE). Manually segmenting each tumor is very cumbersome and very hard to reproduce. To solve the above problem I developed an algorithm, called iterative deconvolution thresholding segmentation (IDTS) algorithm; the algorithm segment the tumor, measures the FV, correct for the PVE and calculates mAC. The algorithm corrects for the PVE without the need to estimate camera’s point spread function (PSF); also does not require optimizing for a specific camera. My algorithm was tested in physical phantom studies, where hollow spheres (0.5-16 ml) were used to represent tumors with a homogeneous activity distribution. It was also tested on irregular shaped tumors with a heterogeneous activity profile which were acquired using physical and simulated phantom. The physical phantom studies were performed with different signal to background ratios (SBR) and with different acquisition times (1-5 min). The algorithm was applied on ten clinical data where the results were compared with manual segmentation and fixed percentage thresholding method called T50 and T60 in which 50% and 60% of the maximum intensity respectively is used as threshold. The average error in FV and mAC calculation was 30% and -35% for 0.5 ml tumor. The average error FV and mAC calculation were ~5% for 16 ml tumor. The overall FV error was ~10% for heterogeneous tumors in physical and simulated phantom data. The FV and mAC error for clinical image compared to manual segmentation was around -17% and 15% respectively. In summary my algorithm has potential to be applied on data acquired from different cameras as its not dependent on knowing the camera’s PSF. The algorithm can also improve dose estimation and treatment planning.

The development of an algorithm to track blood pressure accurately based on the pulse transit time method

Oscillometric blood pressure (BP) monitors are currently used to diagnose hypertension both in home and clinical settings. These monitors take BP measurements once every 15 minutes over a 24 hour period and provide a reliable and accurate system that is minimally invasive. Although intermittent cuff measurements have proven to be a good indicator of BP, a continuous BP monitor is highly desirable for the diagnosis of hypertension and other cardiac diseases. However, no such devices currently exist. A novel algorithm has been developed based on the Pulse Transit Time (PTT) method, which would allow non-invasive and continuous BP measurement. PTT is defined as the time it takes the BP wave to propagate from the heart to a specified point on the body. After an initial BP measurement, PTT algorithms can track BP over short periods of time, known as calibration intervals. After this time has elapsed, a new BP measurement is required to recalibrate the algorithm. Using the PhysioNet database as a basis, the new algorithm was developed and tested using 15 patients, each tested 3 times over a period of 30 minutes. The predicted BP of the algorithm was compared to the arterial BP of each patient. It has been established that this new algorithm is capable of tracking BP over 12 minutes without the need for recalibration, using the BHS standard, a 100% improvement over what has been previously identified. The algorithm was incorporated into a new system based on its requirements and was tested using three volunteers. The results mirrored those previously observed, providing accurate BP measurements when a 12 minute calibration interval was used. This new system provides a significant improvement to the existing method allowing BP to be monitored continuously and non-invasively, on a beat-to-beat basis over 24 hours, adding major clinical and diagnostic value.

Computational tool for three-point hitch geometry optimization

The weight-transfer effect, consisting of the change in dynamic load distribution between the front and the rear tractor axles, is one of the most impairing phenomena for the performance, comfort, and safety of agricultural operations. Excessive weight transfer from the front to the rear tractor axle can occur during operation or maneuvering of implements connected to the tractor through the three-point hitch (TPH). In this respect, an optimal design of the TPH can ensure better dynamic load distribution and ultimately improve operational performance, comfort, and safety. In this study, a computational design tool (The Optimizer) for the determination of a TPH geometry that minimizes the weight-transfer effect is developed. The Optimizer is based on a constrained minimization algorithm. The objective function to be minimized is related to the tractor front-to-rear axle load transfer during a simulated reference maneuver performed with a reference implement on a reference soil. Simulations are based on a 3-degrees-of-freedom (DOF) dynamic model of the tractor-TPH-implement aggregate. The inertial, elastic, and viscous parameters of the dynamic model were successfully determined through a parameter identification algorithm. The geometry determined by the Optimizer complies with the ISO-730 Standard functional requirements and other design requirements. The interaction between the soil and the implement during the simulated reference maneuver was successfully validated against experimental data. Simulation results show that the adopted reference maneuver is effective in triggering the weight-transfer effect, with the front axle load exhibiting a peak-to-peak value of 27.1 kN during the maneuver. A benchmark test was conducted starting from four geometries of a commercially available TPH. As result, all the configurations were optimized by above 10%. The Optimizer, after 36 iterations, was able to find an optimized TPH geometry which allows to reduce the weight-transfer effect by 14.9%.

AGV Safety Areas Obstacle Detection and Interaction with Point Cloud Derived Map

This thesis project aims to the development of an algorithm for the obstacle detection and the interaction between the safety areas of an Automated Guided Vehicles (AGV) and a Point Cloud derived map inside the context of a CAD software. The first part of the project focuses on the implementation of an algorithm for the clipping of general polygons, with which has been possible to: construct the safety areas polygon, derive the sweep of this areas along the navigation path performing a union and detect the intersections with line or polygon representing the obstacles. The second part is about the construction of a map in terms of geometric entities (lines and polygons) starting from a point cloud given by the 3D scan of the environment. The point cloud is processed using: filters, clustering algorithms and concave/convex hull derived algorithms in order to extract line and polygon entities representing obstacles. Finally, the last part aims to use the a priori knowledge of possible obstacle detections on a given segment, to predict the behavior of the AGV and use this prediction to optimize the choice of the vehicle's assigned velocity in that segment, minimizing the travel time.

The Crystal-t Algorithm: A New Approach To Calculate The Sle Of Lipidic Mixtures Presenting Solid Solutions.

Lipidic mixtures present a particular phase change profile highly affected by their unique crystalline structure. However, classical solid-liquid equilibrium (SLE) thermodynamic modeling approaches, which assume the solid phase to be a pure component, sometimes fail in the correct description of the phase behavior. In addition, their inability increases with the complexity of the system. To overcome some of these problems, this study describes a new procedure to depict the SLE of fatty binary mixtures presenting solid solutions, namely the Crystal-T algorithm. Considering the non-ideality of both liquid and solid phases, this algorithm is aimed at the determination of the temperature in which the first and last crystal of the mixture melts. The evaluation is focused on experimental data measured and reported in this work for systems composed of triacylglycerols and fatty alcohols. The liquidus and solidus lines of the SLE phase diagrams were described by using excess Gibbs energy based equations, and the group contribution UNIFAC model for the calculation of the activity coefficients of both liquid and solid phases. Very low deviations of theoretical and experimental data evidenced the strength of the algorithm, contributing to the enlargement of the scope of the SLE modeling.

Post Hoc Analysis Of The Patricia Randomized Trial Of The Efficacy Of Human Papillomavirus Type 16 (hpv-16)/hpv-18 As04-adjuvanted Vaccine Against Incident And Persistent Infection With Nonvaccine Oncogenic Hpv Types Using An Alternative Multiplex Type-specific Pcr Assay For Hpv Dna.

The efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in the Papilloma Trial against Cancer in Young Adults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF10 PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA25) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF10 PCR-DEIA/LiPA25 plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). This post hoc analysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.).

Application Of Laser Microdissection Icp-ms For High Resolution Elemental Mapping In Mouse Brain Tissue: A Comparative Study With Laser Ablation Icp-ms.

Mapping of elements in biological tissue by laser induced mass spectrometry is a fast growing analytical methodology in life sciences. This method provides a multitude of useful information of metal, nonmetal, metalloid and isotopic distribution at major, minor and trace concentration ranges, usually with a lateral resolution of 12-160 µm. Selected applications in medical research require an improved lateral resolution of laser induced mass spectrometric technique at the low micrometre scale and below. The present work demonstrates the applicability of a recently developed analytical methodology - laser microdissection associated to inductively coupled plasma mass spectrometry (LMD ICP-MS) - to obtain elemental images of different solid biological samples at high lateral resolution. LMD ICP-MS images of mouse brain tissue samples stained with uranium and native are shown, and a direct comparison of LMD and laser ablation (LA) ICP-MS imaging methodologies, in terms of elemental quantification, is performed.