Immersive Visualization for Enhanced Computational Fluid Dynamics Analysis

Modern biomedical computer simulations produce spatiotemporal results that are often viewed at a single point in time on standard 2D displays. An immersive visualization environment (IVE) with 3D stereoscopic capability can mitigate some shortcomings of 2D displays via improved depth cues and active movement to further appreciate the spatial localization of imaging data with temporal computational fluid dynamics (CFD) results. We present a semi-automatic workflow for the import, processing, rendering, and stereoscopic visualization of high resolution, patient-specific imaging data, and CFD results in an IVE. Versatility of the workflow is highlighted with current clinical sequelae known to be influenced by adverse hemodynamics to illustrate potential clinical utility

Carotid plaque vulnerability assessment by microscopic morphology analysis, ultrasound and 3D model reconstruction

This thesis was submitted for the degree of Docter of Philosophy and awarded by Brunel University.Research suggests that plaque morphology plays a crucial role in determining plaque vulnerability. However the relationship between plaque morphology and rupture is still not clearly understood due to the limited information of plaque morphology. The aim of this study is to improve our understanding of the relationship between plaque morphology and rupture, and to use this to predict the risk of plaque rupture from the morphology at the molecular level. This can enable the identification of culprit lesions in clinical situations for assessing plaque rupture risk. Histological assessments were carried out on 18 carotid plaque specimens. The 3-D collagen, lipid and macrophage distributions along the entire length of the plaque were analysed in both ruptured and non-ruptured symptomatic plaques. In addition, plaque morphology on the rupture sites were examined and compared with the surrounding regions. It was found that ruptured plaques had thinner fibrous caps and larger lipid cores compared to non-ruptured plaques. Also, ruptured plaques had lower collagen content compared to non-ruptured plaques, and higher collagen contents upstream compared to downstream region from the plaque throat. At the rupture site there was lower collagen content, and a larger lipid core thickness behind a thin fibrous cap compared with the mean for the longitudinally adjacent and circumferential regions. Macrophage cells were located nearer to the boundary of the luminal wall in ruptured plaques. For both groups, the area occupied by macrophages is greater at the upstream shoulder of the plaque. There is a positive correlation between macrophage area and lipid core area, a negative correlation between macrophage area and collagen content, and between lipid core size and collagen content for both plaque groups. 3D reconstruction of ex-vivo specimens of carotid plaques were carried out by a combined analysis of US imaging and histology. To reconstruct accurate 3D plaque morphology, the non-linear tissue distortion in histological images caused by specimen preparation was corrected by a finite element (FE) based deformable registration procedure. This study shows that it is possible to generate a 3D patient specific plaque model using this method. In addition, the study also quantitatively assesses the tissue distortion caused by histological procedures. It shows that at least 30% tissue shrinkage is expected for plaque tissues. The histology analysis result was also used to evaluate ultrasound (US) tissue characterization accuracy. An ex-vivo 2D ultrasound scan set-up was used to obtain serial transverse images through an atherosclerotic plaque. The different plaque component region obtained from ultrasound images was compared with the associated histology result and photograph of the sections. Plaque tissue characterisation using ex-vivo US can be performed qualitatively, whereas lipid core assessment from ultrasound scan can be semi-quantitative. This finding combined with the negative correlation between lipid core size and collagen content, suggests the ability of US to indirectly quantify plaque collagen content. This study may serve as a platform for future studies on improving ultrasound tissue characterization, and may also potentially be used in risk assessment of plaque rupture

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

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

Assessment of the nanomechanical properties of healthy and atherosclerotic coronary arteries by atomic force microscopy

Coronary atherosclerosis is a major cause of mortality and morbidity worldwide. Despite its systemic nature, atherosclerotic plaques form and develop at “predilection” sites often associated with disturbed biomechanical forces. Therefore, computational approaches that analyse the biomechanics (blood flow and tissue mechanics) of atherosclerotic plaques have come to the forefront over the last 20 years. Assignment of appropriate material properties is an integral part of the simulation process. Current approaches for derivation of material properties rely on macro-mechanical testing and are agnostic to local variations of plaque stiffness to which collagen microstructure plays an important role. In this work we used Atomic Force Microscopy to measure the stiffness of healthy and atherosclerotic coronary arteries and we hypothesised that are those are contingent on the local microstructure. Given that the optimal method for studying mechanics of arterial tissue with this method has not been comprehensively established, an indentation protocol was firstly developed and optimised for frozen tissue sections as well as a co-registration framework with the local collagen microstructure utilising the same tissue section for mechanical testing and histological staining for collagen. Overall, the mechanical properties (Young’s Modulus) of the healthy vessel wall (median = 11.0 kPa, n=1379 force curves) were found to be significantly stiffer (p=1.3410-10) than plaque tissue (median=4.3 kPa, n=1898 force curves). Within plaques, lipid-rich areas (median=2.2 kPa, n=392 force curves) were found significantly softer (p=1.4710-4) than areas rich in collagen, such as the fibrous cap (median=4.9 kPa, n=1506 force curves). No statistical difference (p=0.89) was found between measurements in the middle of the fibrous cap (median=4.8 kPa, n=868 force curves) and the cap shoulder (median=5.1 kPa, n=638 force curves). Macro-mechanical testing methods dominate the entire landscape of material testing techniques. Plaques are very heterogenous in composition and macro-mechanical methods are agnostic to microscale variations in plaque stiffness. Mechanical testing by indentation may be better suited to quantify local variations in plaque stiffness, that are potent drivers of plaque rupture.Open Acces

Multi-contrast atherosclerosis characterization (MATCH) of carotid plaque with a single 5-min scan: technical development and clinical feasibility

BACKGROUND: Multi-contrast weighted imaging is a commonly used cardiovascular magnetic resonance (CMR) protocol for characterization of carotid plaque composition. However, this approach is limited in several aspects including low slice resolution, long scan time, image mis-registration, and complex image interpretation. In this work, a 3D CMR technique, named Multi-contrast Atherosclerosis Characterization (MATCH), was developed to mitigate the above limitations. METHODS: MATCH employs a 3D spoiled segmented fast low angle shot readout to acquire data with three different contrast weightings in an interleaved fashion. The inherently co-registered image sets, hyper T1-weighting, gray blood, and T2-weighting, are used to detect intra-plaque hemorrhage (IPH), calcification (CA), lipid-rich necrotic core (LRNC), and loose-matrix (LM). The MATCH sequence was optimized by computer simulations and testing on four healthy volunteers and then evaluated in a pilot study of six patients with carotid plaque, using the conventional multi-contrast protocol as a reference. RESULTS: On MATCH images, the major plaque components were easy to identify. Spatial co-registration between the three image sets with MATCH was particularly helpful for the reviewer to discern co-existent components in an image and appreciate their spatial relation. Based on Cohen’s kappa tests, moderate to excellent agreement in the image-based or artery-based component detection between the two protocols was obtained for LRNC, IPH, CA, and LM, respectively. Compared with the conventional multi-contrast protocol, the MATCH protocol yield significantly higher signal contrast ratio for IPH (3.1 ± 1.3 vs. 0.4 ± 0.3, p < 0.001) and CA (1.6 ± 1.5 vs. 0.7 ± 0.6, p = 0.012) with respect to the vessel wall. CONCLUSIONS: To the best of our knowledge, the proposed MATCH sequence is the first 3D CMR technique that acquires spatially co-registered multi-contrast image sets in a single scan for characterization of carotid plaque composition. Our pilot clinical study suggests that the MATCH-based protocol may outperform the conventional multi-contrast protocol in several respects. With further technical improvements and large-scale clinical validation, MATCH has the potential to become a CMR method for assessing the risk of plaque disruption in a clinical workup

Carotid plaque stress analysis by fluid structure interaction based on in-vivo MRI: Implications to plaque vulnerability assessment

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University, 2010.Stroke is one of the leading causes of death in the world, resulting mostly from the sudden rupture of atherosclerotic plaques. From a biomechanical view, plaque rupture can be considered as a mechanical failure caused by extremely high plaque stress. In this PhD project, we are aiming to predict 3D plaque stress based on in-vivo MRI by using fluid structure interaction (FSI) method, and provide information for plaque rupture risk assessment. Fluid structure interaction was implemented with ANSYS 11.0, followed by a parameter study on fibrous cap thickness and lipid core size with realistic carotid plaque geometry. Twenty patients with carotid plaques imaged by in-vivo MRI were provided in the project. A framework of reconstructing 3D plaque geometry from in-vivo multispectral MRI was designed. The followed reproducibility study on plaque geometry reconstruction procedure and its effect on plaque stress analysis filled the gap in the literature on imaging based plaque stress modeling. The results demonstrated that current MRI technology can provide sufficient information for plaque structure characterization; however stress analysis result is highly affected by MRI resolution and quality. The application of FSI stress analysis to 4 patients with different plaque burdens has showed that the whole procedure from plaque geometry reconstruction to FSI stress analysis was applicable. In the study, plaque geometries from three patients with recent transient ischemic attack were reconstructed by repairing ruptured fibrous cap. The well correlated relationship between local stress concentrations and plaque rupture sites indicated that extremely high plaque stress could be a factor responsible for plaque rupture. Based on the 20 reconstructed carotid plaques from two groups (symptomatic and asymptomatic), fully coupled fluid structure interaction was performed. It was found that there is a significant difference between symptomatic and asymptomatic patients in plaque stress levels, indicating plaque stress could be used as one of the factors for plaque vulnerability assessment. A corresponding plaque morphological feature study showed that plaque stress is significantly affected by fibrous cap thickness, lipid core size and fibrous cap surface irregularities (curvedness). A procedure was proposed for predicting plaque stress by using fibrous cap thickness and curvedness, which requires much less computational time, and has the potential for clinical routine application. The effects of residual stress on plaque stress analysis and arterial wall material property characterization by using in-vivo MRI data were also discussed for patient specific modeling. As the further development, histological study of plaque sample has been combined with conventional plaque stress analysis by assigning material properties to each computational element, based on the data from histological analysis. This method could bridge the gap between biochemistry and biomechanical study of atherosclerosis plaques. In conclusion, extreme stress distributions in the plaque region can be predicted by modern numerical methods, and used for plaque rupture risk assessment, which will be helpful in clinical practice. The combination of plaque MR imaging analysis, computational modelling, and clinical study/ validation would advance our understandings of plaque rupture, prediction of future rupture, and establish new procedures for patient diagnose, management, and treatment.Financial Support was obtained from British Heart Foundation, Brunel Institute for Bioengineering and Brunel Graduate School