Basic Science to Clinical Research: Segmentation of Ultrasound and Modelling in Clinical Informatics

The world of basic science is a world of minutia; it boils down to improving even a fraction of a percent over the baseline standard. It is a domain of peer reviewed fractions of seconds and the world of squeezing every last ounce of efficiency from a processor, a storage medium, or an algorithm. The field of health data is based on extracting knowledge from segments of data that may improve some clinical process or practice guideline to improve the time and quality of care. Clinical informatics and knowledge translation provide this information in order to reveal insights to the world of improving patient treatments, regimens, and overall outcomes. In my world of minutia, or basic science, the movement of blood served an integral role. The novel detection of sound reverberations map out the landscape for my research. I have applied my algorithms to the various anatomical structures of the heart and artery system. This serves as a basis for segmentation, active contouring, and shape priors. The algorithms presented, leverage novel applications in segmentation by using anatomical features of the heart for shape priors and the integration of optical flow models to improve tracking. The presented techniques show improvements over traditional methods in the estimation of left ventricular size and function, along with plaque estimation in the carotid artery. In my clinical world of data understanding, I have endeavoured to decipher trends in Alzheimer’s disease, Sepsis of hospital patients, and the burden of Melanoma using mathematical modelling methods. The use of decision trees, Markov models, and various clustering techniques provide insights into data sets that are otherwise hidden. Finally, I demonstrate how efficient data capture from providers can achieve rapid results and actionable information on patient medical records. This culminated in generating studies on the burden of illness and their associated costs. A selection of published works from my research in the world of basic sciences to clinical informatics has been included in this thesis to detail my transition. This is my journey from one contented realm to a turbulent one

Artificial intelligence and automation in valvular heart diseases

Artificial intelligence (AI) is gradually changing every aspect of social life, and healthcare is no exception. The clinical procedures that were supposed to, and could previously only be handled by human experts can now be carried out by machines in a more accurate and efficient way. The coming era of big data and the advent of supercomputers provides great opportunities to the development of AI technology for the enhancement of diagnosis and clinical decision-making. This review provides an introduction to AI and highlights its applications in the clinical flow of diagnosing and treating valvular heart diseases (VHDs). More specifically, this review first introduces some key concepts and subareas in AI. Secondly, it discusses the application of AI in heart sound auscultation and medical image analysis for assistance in diagnosing VHDs. Thirdly, it introduces using AI algorithms to identify risk factors and predict mortality of cardiac surgery. This review also describes the state-of-the-art autonomous surgical robots and their roles in cardiac surgery and intervention

State of the Art of Level Set Methods in Segmentation and Registration of Medical Imaging Modalities

Segmentation of medical images is an important step in various applications such as visualization, quantitative analysis and image-guided surgery. Numerous segmentation methods have been developed in the past two decades for extraction of organ contours on medical images. Low-level segmentation methods, such as pixel-based clustering, region growing, and filter-based edge detection, require additional pre-processing and post-processing as well as considerable amounts of expert intervention or information of the objects of interest. Furthermore the subsequent analysis of segmented objects is hampered by the primitive, pixel or voxel level representations from those region-based segmentation. Deformable models, on the other hand, provide an explicit representation of the boundary and the shape of the object. They combine several desirable features such as inherent connectivity and smoothness, which counteract noise and boundary irregularities, as well as the ability to incorporate knowledge about the object of interest. However, parametric deformable models have two main limitations. First, in situations where the initial model and desired object boundary differ greatly in size and shape, the model must be re-parameterized dynamically to faithfully recover the object boundary. The second limitation is that it has difficulty dealing with topological adaptation such as splitting or merging model parts, a useful property for recovering either multiple objects or objects with unknown topology. This difficulty is caused by the fact that a new parameterization must be constructed whenever topology change occurs, which requires sophisticated schemes. Level set deformable models, also referred to as geometric deformable models, provide an elegant solution to address the primary limitations of parametric deformable models. These methods have drawn a great deal of attention since their introduction in 1988. Advantages of the contour implicit formulation of the deformable model over parametric formulation include: (1) no parameterization of the contour, (2) topological flexibility, (3) good numerical stability, (4) straightforward extension of the 2D formulation to n-D. Recent reviews on the subject include papers from Suri. In this chapter we give a general overview of the level set segmentation methods with emphasize on new frameworks recently introduced in the context of medical imaging problems. We then introduce novel approaches that aim at combining segmentation and registration in a level set formulation. Finally we review a selective set of clinical works with detailed validation of the level set methods for several clinical applications

Semi-automatic algorithm for construction of the left ventricular area variation curve over a complete cardiac cycle

<p>Abstract</p> <p>Background</p> <p>Two-dimensional echocardiography (2D-echo) allows the evaluation of cardiac structures and their movements. A wide range of clinical diagnoses are based on the performance of the left ventricle. The evaluation of myocardial function is typically performed by manual segmentation of the ventricular cavity in a series of dynamic images. This process is laborious and operator dependent. The automatic segmentation of the left ventricle in 4-chamber long-axis images during diastole is troublesome, because of the opening of the mitral valve.</p> <p>Methods</p> <p>This work presents a method for segmentation of the left ventricle in dynamic 2D-echo 4-chamber long-axis images over the complete cardiac cycle. The proposed algorithm is based on classic image processing techniques, including time-averaging and wavelet-based denoising, edge enhancement filtering, morphological operations, homotopy modification, and watershed segmentation. The proposed method is semi-automatic, requiring a single user intervention for identification of the position of the mitral valve in the first temporal frame of the video sequence. Image segmentation is performed on a set of dynamic 2D-echo images collected from an examination covering two consecutive cardiac cycles.</p> <p>Results</p> <p>The proposed method is demonstrated and evaluated on twelve healthy volunteers. The results are quantitatively evaluated using four different metrics, in a comparison with contours manually segmented by a specialist, and with four alternative methods from the literature. The method's intra- and inter-operator variabilities are also evaluated.</p> <p>Conclusions</p> <p>The proposed method allows the automatic construction of the area variation curve of the left ventricle corresponding to a complete cardiac cycle. This may potentially be used for the identification of several clinical parameters, including the area variation fraction. This parameter could potentially be used for evaluating the global systolic function of the left ventricle.</p

Doctor of Philosophy

dissertationCongenital heart defects are classes of birth defects that affect the structure and function of the heart. These defects are attributed to the abnormal or incomplete development of a fetal heart during the first few weeks following conception. The overall detection rate of congenital heart defects during routine prenatal examination is low. This is attributed to the insufficient number of trained personnel in many local health centers where many cases of congenital heart defects go undetected. This dissertation presents a system to identify congenital heart defects to improve pregnancy outcomes and increase their detection rates. The system was developed and its performance assessed in identifying the presence of ventricular defects (congenital heart defects that affect the size of the ventricles) using four-dimensional fetal chocardiographic images. The designed system consists of three components: 1) a fetal heart location estimation component, 2) a fetal heart chamber segmentation component, and 3) a detection component that detects congenital heart defects from the segmented chambers. The location estimation component is used to isolate a fetal heart in any four-dimensional fetal echocardiographic image. It uses a hybrid region of interest extraction method that is robust to speckle noise degradation inherent in all ultrasound images. The location estimation method's performance was analyzed on 130 four-dimensional fetal echocardiographic images by comparison with manually identified fetal heart region of interest. The location estimation method showed good agreement with the manually identified standard using four quantitative indexes: Jaccard index, Sørenson-Dice index, Sensitivity index and Specificity index. The average values of these indexes were measured at 80.70%, 89.19%, 91.04%, and 99.17%, respectively. The fetal heart chamber segmentation component uses velocity vector field estimates computed on frames contained in a four-dimensional image to identify the fetal heart chambers. The velocity vector fields are computed using a histogram-based optical flow technique which is formulated on local image characteristics to reduces the effect of speckle noise and nonuniform echogenicity on the velocity vector field estimates. Features based on the velocity vector field estimates, voxel brightness/intensity values, and voxel Cartesian coordinate positions were extracted and used with kernel k-means algorithm to identify the individual chambers. The segmentation method's performance was evaluated on 130 images from 31 patients by comparing the segmentation results with manually identified fetal heart chambers. Evaluation was based on the Sørenson-Dice index, the absolute volume difference and the Hausdorff distance, with each resulting in per patient average values of 69.92%, 22.08%, and 2.82 mm, respectively. The detection component uses the volumes of the identified fetal heart chambers to flag the possible occurrence of hypoplastic left heart syndrome, a type of congenital heart defect. An empirical volume threshold defined on the relative ratio of adjacent fetal heart chamber volumes obtained manually is used in the detection process. The performance of the detection procedure was assessed by comparison with a set of images with confirmed diagnosis of hypoplastic left heart syndrome and a control group of normal fetal hearts. Of the 130 images considered 18 of 20 (90%) fetal hearts were correctly detected as having hypoplastic left heart syndrome and 84 of 110 (76.36%) fetal hearts were correctly detected as normal in the control group. The results show that the detection system performs better than the overall detection rate for congenital heart defect which is reported to be between 30% and 60%

Fast catheter segmentation and tracking based on x-ray fluoroscopic and echocardiographic modalities for catheter-based cardiac minimally invasive interventions

X-ray fluoroscopy and echocardiography imaging (ultrasound, US) are two imaging modalities that are widely used in cardiac catheterization. For these modalities, a fast, accurate and stable algorithm for the detection and tracking of catheters is required to allow clinicians to observe the catheter location in real-time. Currently X-ray fluoroscopy is routinely used as the standard modality in catheter ablation interventions. However, it lacks the ability to visualize soft tissue and uses harmful radiation. US does not have these limitations but often contains acoustic artifacts and has a small field of view. These make the detection and tracking of the catheter in US very challenging. The first contribution in this thesis is a framework which combines Kalman filter and discrete optimization for multiple catheter segmentation and tracking in X-ray images. Kalman filter is used to identify the whole catheter from a single point detected on the catheter in the first frame of a sequence of x-ray images. An energy-based formulation is developed that can be used to track the catheters in the following frames. We also propose a discrete optimization for minimizing the energy function in each frame of the X-ray image sequence. Our approach is robust to tangential motion of the catheter and combines the tubular and salient feature measurements into a single robust and efficient framework. The second contribution is an algorithm for catheter extraction in 3D ultrasound images based on (a) the registration between the X-ray and ultrasound images and (b) the segmentation of the catheter in X-ray images. The search space for the catheter extraction in the ultrasound images is constrained to lie on or close to a curved surface in the ultrasound volume. The curved surface corresponds to the back-projection of the extracted catheter from the X-ray image to the ultrasound volume. Blob-like features are detected in the US images and organized in a graphical model. The extracted catheter is modelled as the optimal path in this graphical model. Both contributions allow the use of ultrasound imaging for the improved visualization of soft tissue. However, X-ray imaging is still required for each ultrasound frame and the amount of X-ray exposure has not been reduced. The final contribution in this thesis is a system that can track the catheter in ultrasound volumes automatically without the need for X-ray imaging during the tracking. Instead X-ray imaging is only required for the system initialization and for recovery from tracking failures. This allows a significant reduction in the amount of X-ray exposure for patient and clinicians.Open Acces

Multidimensional image analysis of cardiac function in MRI

Cardiac morphology is a key indicator of cardiac health. Important metrics that are currently in clinical use are left-ventricle cardiac ejection fraction, cardiac muscle (myocardium) mass, myocardium thickness and myocardium thickening over the cardiac cycle. Advances in imaging technologies have led to an increase in temporal and spatial resolution. Such an increase in data presents a laborious task for medical practitioners to analyse. In this thesis, measurement of the cardiac left-ventricle function is achieved by developing novel methods for the automatic segmentation of the left-ventricle blood-pool and the left ventricle myocardium boundaries. A preliminary challenge faced in this task is the removal of noise from Magnetic Resonance Imaging (MRI) data, which is addressed by using advanced data filtering procedures. Two mechanisms for left-ventricle segmentation are employed. Firstly segmentation of the left ventricle blood-pool for the measurement of ejection fraction is undertaken in the signal intensity domain. Utilising the high discrimination between blood and tissue, a novel methodology based on a statistical partitioning method offers success in localising and segmenting the blood pool of the left ventricle. From this initialisation, the estimation of the outer wall (epi-cardium) of the left ventricle can be achieved using gradient information and prior knowledge. Secondly, a more involved method for extracting the myocardium of the leftventricle is developed, that can better perform segmentation in higher dimensions. Spatial information is incorporated in the segmentation by employing a gradient-based boundary evolution. A level-set scheme is implemented and a novel formulation for the extraction of the cardiac muscle is introduced. Two surfaces, representing the inner and the outer boundaries of the left-ventricle, are simultaneously evolved using a coupling function and supervised with a probabilistic model of expertly assisted manual segmentations

Kinematic Modeling of the Determinants of Diastolic Function

Multiple modalities are routinely used in clinical cardiology to determine cardiovascular function, and many of the indexes derived from these modalities are causally interconnected. A correlative approach to cardiovascular function however, where indexes are correlated to disease presence and progression, fails to fully capitalize on the information content of the indexes. Causal quantitative modeling of cardiovascular physiology on the other hand offers a predictive rather than accommodative approach to cardiovascular function determination. In this work we apply a kinematic modeling approach to understanding diastolic function. We discuss novel insights related to the physiological determinants of diastolic function, and define novel causal indexes of diastolic function that go beyond the limitations of current established clinical indexes. Diastolic function is typically characterized by physiologists and cardiologists as being determined by the interplay between chamber stiffness, chamber relaxation/viscoelasticity, and chamber filling volume or load. In this work we provide kinematic modeling based analysis of each of these clinical diastolic function determinants. Considering the kinematic elastic (stiffness) components of filling, we argue for the universality of diastolic suction and define a novel in-vivo equilibrium volume. Application of this novel equilibrium volume in the clinical setting results in a novel approach to determination of global chamber stiffness. Considering the viscoelastic components of filling, we demonstrate the limitations associated with ignoring viscoelastic effects, an assumption often made in the clinical setting. We extend the viscoelastic component of filling into the invasive hemodynamic domain, and demonstrate the causal link between invasively recorded LV pressure and noninvasively recorded transmitral flow by describing a method for extracting flow contours from pressure signals alone. Finally, in considering load, we solve the problem of load dependence in diastolic function analysis. Indeed all traditional clinical indexes of diastolic function are load dependent, and therefore are imperfect indexes of intrinsic diastolic function. Applying kinematic modeling, we derive a load independent index of diastolic function. Validation involves showing that the index is indeed load-independent and can differentiate between control and diastolic dysfunction states. We apply this novel analysis to derive surrogates for filling pressure, and generalize the kinematic modeling approach to the analysis of isovolumic relaxation. To aid widespread adoption of the load independent index, we derive and validate simplified expressions for model-based physiological parameters of diastolic function. Our goal is to provide a causal approach to cardiovascular function analysis based on how things move, to explain prior phenomenological observations of others under a single causal paradigm, to discover `new physiology\u27, facilitate the discovery of more robust indexes of cardiovascular function, and provide a means for widespread adoption of the kinematic modeling approach suitable for the general clinical setting