Computer assisted analysis of contrast enhanced ultrasound images for quantification in vascular diseases

Contrast enhanced ultrasound (CEUS) with microbubble contrast agents has shown great potential in imaging microvasculature, quantifying perfusion and hence detecting vascular diseases. However, most existing perfusion quantification methods based on image intensity, and are susceptible to confounding factors such as attenuation artefacts. Improving reproducibility is also a key challenge to clinical translation. Therefore, this thesis aims at developing attenuation correction and quantification techniques in CEUS with applications for detection and quantification of microvascular flow / perfusion. Firstly, a technique for automatic correction of attenuation effects in vascular imaging was developed and validated on a tissue mimicking phantom. The application of this technique to studying contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis was demonstrated. The results showed great potential in reducing attenuation artefact and improve quantification in CEUS of carotid arteries. Furthermore, contrast intensity was shown to significantly increase in irradiated carotid arteries and could be a useful imaging biomarker for radiation-induced atherosclerosis. Secondly, a robust and automated tool for quantification of microbubble identification in CEUS image sequences using a temporal and spatial analysis was developed and validated on a flow phantom. The application of this technique to evaluate human musculoskeletal microcirculation with contrast enhanced ultrasound was demonstrated. The results showed an excellent accuracy and repeatability in quantifying active vascular density. It has great potential for clinical translation in the assessment of lower limb perfusion. Finally, a new bubble activity identification and quantification technique based on differential intensity projection in CEUS was developed and demonstrated with an in-vivo study, and applied to the quantification of intraplaque neovascularisation in an irradiated carotid artery of patients who were previously treated for head and neck cancer. The results showed a significantly more specific identification of bubble signals and had good agreement between the differential intensity-based technique and clinical visual assessment. This technique has potential to assist clinicians to diagnose and monitor intraplque neovascularisation.Open Acces

Image Analysis of the Carotid Artery: A (Semi-)Automatic Approach

In this thesis we presented several (semi-)automatic image processing techniques for analyzing the carotid artery wall and carotid artery plaque in MRI and Ultrasound. The presented methods include image segmentation, registration, centerline extraction, and quantification

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Preoperative Systems for Computer Aided Diagnosis based on Image Registration: Applications to Breast Cancer and Atherosclerosis

Computer Aided Diagnosis (CAD) systems assist clinicians including radiologists and cardiologists to detect abnormalities and highlight conspicuous possible disease. Implementing a pre-operative CAD system contains a framework that accepts related technical as well as clinical parameters as input by analyzing the predefined method and demonstrates the prospective output. In this work we developed the Computer Aided Diagnostic System for biomedical imaging analysis of two applications on Breast Cancer and Atherosclerosis. The aim of the first CAD application is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. Base on the fact that automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70±0.03, 0.74±0.03 and 0.81±0.09 (out of 1) for Affine, BSpline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation. The aim of the second implemented CAD application is to assess contribution of calcification in plaque vulnerability and wall rupture and to find its maximum resistance before break in image-based models of carotid artery stenting. The role of calcification inside fibroatheroma during carotid artery stenting operation is controversial in which cardiologists face two major problems during the placement: (i) “plaque protrusion” (i.e. elastic fibrous caps containing early calcifications that penetrate inside the stent); (ii) “plaque vulnerability” (i.e. stiff plaques with advanced calcifications that break the arterial wall or stent). Finite Element Analysis was used to simulate the balloon and stent expansion as a preoperative patient-specific virtual framework. A nonlinear static structural analysis was performed on 20 patients acquired using in vivo MDCT angiography. The Agatston Calcium score was obtained for each patient and subject-specific local Elastic Modulus (EM) was calculated. The in silico results showed that by imposing average ultimate external load of 1.1MPa and 2.3MPa on balloon and stent respectively, average ultimate stress of 55.7±41.2kPa and 171±41.2kPa are obtained on calcifications. The study reveals that a significant positive correlation (R=0.85, p<0.0001) exists on stent expansion between EM of calcification and ultimate stress as well as Plaque Wall Stress (PWS) (R=0.92, p<0.0001), comparing to Ca score that showed insignificant associations with ultimate stress (R=0.44, p=0.057) and PWS (R=0.38, p=0.103), suggesting minor impact of Ca score in plaque rupture. These average data are in good agreement with results obtained by other research groups and we believe this approach enriches the arsenal of tools available for pre-operative prediction of carotid artery stenting procedure in the presence of calcified plaques

Vascular Segmentation Algorithms for Generating 3D Atherosclerotic Measurements

Atherosclerosis manifests as plaques within large arteries of the body and remains as a leading cause of mortality and morbidity in the world. Major cardiovascular events may occur in patients without known preexisting symptoms, thus it is important to monitor progression and regression of the plaque burden in the arteries for evaluating patient\u27s response to therapy. In this dissertation, our main focus is quantification of plaque burden from the carotid and femoral arteries, which are major sites for plaque formation, and are straight forward to image noninvasively due to their superficial location. Recently, 3D measurements of plaque burden have shown to be more sensitive to the changes of plaque burden than one-/two-dimensional measurements. However, despite the advancements of 3D noninvasive imaging technology with rapid acquisition capabilities, and the high sensitivity of the 3D plaque measurements of plaque burden, they are still not widely used due to the inordinate amount of time and effort required to delineate artery walls plus plaque boundaries to obtain 3D measurements from the images. Therefore, the objective of this dissertation is developing novel semi-automated segmentation methods to alleviate measurement burden from the observer for segmentation of the outer wall and lumen boundaries from: (1) 3D carotid ultrasound (US) images, (2) 3D carotid black-blood magnetic resonance (MR) images, and (3) 3D femoral black-blood MR images. Segmentation of the carotid lumen and outer wall from 3DUS images is a challenging task due to low image contrast, for which no method has been previously reported. Initially, we developed a 2D slice-wise segmentation algorithm based on the level set method, which was then extended to 3D. The 3D algorithm required fewer user interactions than manual delineation and the 2D method. The algorithm reduced user time by ≈79% (1.72 vs. 8.3 min) compared to manual segmentation for generating 3D-based measurements with high accuracy (Dice similarity coefficient (DSC)\u3e90%). Secondly, we developed a novel 3D multi-region segmentation algorithm, which simultaneously delineates both the carotid lumen and outer wall surfaces from MR images by evolving two coupled surfaces using a convex max-flow-based technique. The algorithm required user interaction only on a single transverse slice of the 3D image for generating 3D surfaces of the lumen and outer wall. The algorithm was parallelized using graphics processing units (GPU) to increase computational speed, thus reducing user time by 93% (0.78 vs. 12 min) compared to manual segmentation. Moreover, the algorithm yielded high accuracy (DSC \u3e 90%) and high precision (intra-observer CV \u3c 5.6% and inter-observer CV \u3c 6.6%). Finally, we developed and validated an algorithm based on convex max-flow formulation to segment the femoral arteries that enforces a tubular shape prior and an inter-surface consistency of the outer wall and lumen to maintain a minimum separation distance between the two surfaces. The algorithm required the observer to choose only about 11 points on its medial axis of the artery to yield the 3D surfaces of the lumen and outer wall, which reduced the operator time by 97% (1.8 vs. 70-80 min) compared to manual segmentation. Furthermore, the proposed algorithm reported DSC greater than 85% and small intra-observer variability (CV ≈ 6.69%). In conclusion, the development of robust semi-automated algorithms for generating 3D measurements of plaque burden may accelerate translation of 3D measurements to clinical trials and subsequently to clinical care