Analysis of myocardial contractility with magnetic resonance

Heart failure has considerable morbidity and poor prognosis. An understanding of the underlying mechanics governing myocardial contraction is a prerequisite for interpreting and predicting changes induced by heart disease. Gross changes in contractile behaviour of the myocardium are readily detected with existing techniques. For more subtle changes during early stages of cardiac dysfunction, however, it requires a sensitive method for measuring, as well as a precise criterion for quantifying, normal and impaired myocardial function. Cardiovascular Magnetic Resonance (CMR) imaging is emerging as an important clinical tool because of its safety, versatility, and the high quality images it produces that allow accurate and reproducible quantification of cardiac structure and function. Traditional CMR approaches for measuring contractility rely on tagging of the myocardium with fiducial markers and require a lengthy and often subjective dependant post-processing procedure. The aim of this research is to develop a new technique, which uses velocity as a marker for the visualisation and assessment of myocardial contractility. Two parallel approaches have been investigated for the assessment of myocardial velocity. The first of these is haimonic phase (HARP) imaging. HARP imaging allows direct derivation of myocardial velocity and strain without the need of further user interaction. We investigated the effect of respiration on the accuracy of the derived contractility, and assessed the clinical applicability and potential pitfalls of the technique by analysing results from a group of patients with hypertrophic cardiomyopathy. The second technique we have investigated is the direct measurement of myocardial velocity with phase contrast myocardial velocity mapping. The imaging sequence used employs effective blood saturation for reducing flow induced phase errors within the myocardium. View sharing was used to improve the temporal resolution, which permitted acquisition of 3D velocity information throughout the cardiac cycle in a single breath-hold, enabling a comprehensive assessment of strain rate of the left ventricle. One key factor that affects the derivation of myocardial contractility based on myocardial velocity is the practical inconsistency of the velocity data. A novel iterative optimisation scheme by incorporating the incompressibility constraint was developed for the restoration of myocardial velocity data. The method allowed accurate assessment of both in-plane and through-plan strain rates, as demonstrated with both synthetic and in vivo data acquired from normal subjects and ischaemic patients. To further enhance the clinical potential of the technique and facilitate the visual assessment of contractile abnormality with myocardial velocity mapping, a complementary analysis framework, named Virtual Tagging, has been developed. The method used velocity data in all directions combined with a finite element mesh incorporating geometrical and physical constraints. The Virtual Tagging framewoik allowed velocity measurements to be used for calculating strain distribution within the 3D volume. It also permitted easy visualisation of the displacement of the tissue, akin to traditional CMR tagging. Detailed validation of the technique is provided, which involves both numerical simulation and in vitro phantom experiments. The main contribution of this thesis is in the improvement of the effectiveness and quality of quantitative myocardial contractility analysis from both sequence design and medical image computing perspectives. It is aimed at providing a sensitive means of detecting subtle as well as gross changes in contractile behaviour of the myocardium. The study is expected to provide a clinically viable platform for functional correlation with other functional measures such as myocardial perfusion and diffusion, and to serve as an aid for further understanding of the links between intrinsicOpen acces

Analysis of cardiac motion using MRI and nonrigid image registration

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Flow pattern analysis for magnetic resonance velocity imaging

Blood flow in the heart is highly complex. Although blood flow patterns have been investigated by both computational modelling and invasive/non-invasive imaging techniques, their evolution and intrinsic connection with cardiovascular disease has yet to be explored. Magnetic resonance (MR) velocity imaging provides a comprehensive distribution of multi-directional in vivo flow distribution so that detailed quantitative analysis of flow patterns is now possible. However, direct visualisation or quantification of vector fields is of little clinical use, especially for inter-subject or serial comparison of changes in flow patterns due to the progression of the disease or in response to therapeutic measures. In order to achieve a comprehensive and integrated description of flow in health and disease, it is necessary to characterise and model both normal and abnormal flows and their effects. To accommodate the diversity of flow patterns in relation to morphological and functional changes, we have described in this thesis an approach of detecting salient topological features prior to analytical assessment of dynamical indices of the flow patterns. To improve the accuracy of quantitative analysis of the evolution of topological flow features, it is essential to restore the original flow fields so that critical points associated with salient flow features can be more reliably detected. We propose a novel framework for the restoration, abstraction, extraction and tracking of flow features such that their dynamic indices can be accurately tracked and quantified. The restoration method is formulated as a constrained optimisation problem to remove the effects of noise and to improve the consistency of the MR velocity data. A computational scheme is derived from the First Order Lagrangian Method for solving the optimisation problem. After restoration, flow abstraction is applied to partition the entire flow field into clusters, each of which is represented by a local linear expansion of its velocity components. This process not only greatly reduces the amount of data required to encode the velocity distribution but also permits an analytical representation of the flow field from which critical points associated with salient flow features can be accurately extracted. After the critical points are extracted, phase portrait theory can be applied to separate them into attracting/repelling focuses, attracting/repelling nodes, planar vortex, or saddle. In this thesis, we have focused on vortical flow features formed in diastole. To track the movement of the vortices within a cardiac cycle, a tracking algorithm based on relaxation labelling is employed. The constraints and parameters used in the tracking algorithm are designed using the characteristics of the vortices. The proposed framework is validated with both simulated and in vivo data acquired from patients with sequential MR examination following myocardial infarction. The main contribution of the thesis is in the new vector field restoration and flow feature abstraction method proposed. They allow the accurate tracking and quantification of dynamic indices associated with salient features so that inter- and intra-subject comparisons can be more easily made. This provides further insight into the evolution of blood flow patterns and permits the establishment of links between blood flow patterns and localised genesis and progression of cardiovascular disease.Open acces

Atlas construction and image analysis using statistical cardiac models

International audienceThis paper presents a brief overview of current trends in the construction of population and multi-modal heart atlases in our group and their application to atlas-based cardiac image analysis. The technical challenges around the construction of these atlases are organized around two main axes: groupwise image registration of anatomical, motion and fiber images and construction of statistical shape models. Application-wise, this paper focuses on the extraction of atlas-based biomarkers for the detection of local shape or motion abnormalities, addressing several cardiac applications where the extracted information is used to study and grade different pathologies. The paper is concluded with a discussion about the role of statistical atlases in the integration of multiple information sources and the potential this can bring to in-silico simulations

Medical image segmentation and analysis using statistical shape modelling and inter-landmark relationships

The study of anatomical morphology is of great importance to medical imaging, with applications varying from clinical diagnosis to computer-aided surgery. To this end, automated tools are required for accurate extraction of the anatomical boundaries from the image data and detailed interpretation of morphological information. This thesis introduces a novel approach to shape-based analysis of medical images based on Inter- Landmark Descriptors (ILDs). Unlike point coordinates that describe absolute position, these shape variables represent relative configuration of landmarks in the shape. The proposed work is motivated by the inherent difficulties of methods based on landmark coordinates in challenging applications. Through explicit invariance to pose parameters and decomposition of the global shape constraints, this work permits anatomical shape analysis that is resistant to image inhomogeneities and geometrical inconsistencies. Several algorithms are presented to tackle specific image segmentation and analysis problems, including automatic initialisation, optimal feature point search, outlier handling and dynamic abnormality localisation. Detailed validation results are provided based on various cardiovascular magnetic resonance datasets, showing increased robustness and accuracy.Open acces

Computer-aided detection of wall motion abnormalities in cardiac MRI

With the increasing prevalence and hospitalization rate of ischaemic heart disease, an explosive growth of diagnostic imaging for ischaemia is ongoing. Clinical decision making on revascularization procedures requires reliable viability assessment to assure long-term patient survival and to elevate cost effectiveness of the therapy and treatment. As such, the demand is increasing for a computer-assisted diagnosis (CAD) method for ischaemic heart disease that supports clinicians with an objective analysis of infarct severity, a viability assessment or a prediction of potential functional improvement before performing revascularization. The goal of this thesis was to explore novel mechanisms that can be used for CAD in ischaemic heart disease, particularly through wall motion analysis from cardiac MR images. Existing diagnostic treatment of wall motion analysis from cardiac MR relies on visual wall motion scoring, which suffers from inter- and intra-observer variability. To minimize this variability, the automated method must contain essential knowledge on how the heart contracts normally. This enables automatic quantification of regional abnormal wall motion, detection of segments with contractile reserve and prediction of functional improvement in stress.1. Bontius Stichting inz. Doelfonds beeldverwerking, 2. Foundation Imago, 3. ASCI research school, and 4. Library of the University of Leiden.UBL - phd migration 201

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

Shockwave for abrogation of heart failure in ischaemia-reperfusion injury

BACKGROUND: Although reperfusion of STEMI has markedly improved acute patients’ survival, more patients are living with heart failure. Theoretically, more myocardial tissue is salvageable if reperfusion injury could be alleviated, limiting the risk of developing heart failure. AIM: To assess the combination shockwave treatment with DPP4-inhibitor as a treatment adjunct for cardiac IR injury. HYPOTHESIS: Shockwave provides cardioprotection from IR injury, improves cardiac function and cell-homing, and when shockwave used in conjunction with DPP4-inhibitor, the effects are augmented. METHOD: In-vivo: Surgical IR-rat models imaged using Bruker-BioSpec-9.4T. Multi-sequence CMR similar to clinical multi-planar acquisition using: (a) FLASH-CINE, (b) INTRAGATE-CINE, (c) MESE-T2-map, (d) T2-star, and (e) IR-LGE; in experimental groups: (1) Healthy versus IR-MI [a,b,c,e]; (2) Healthy versus Healthy-SW [a,b] ; (3) Healthy-SW versus Healthy-SW-inhibitor [a]; (4) IR-MI versus IR-MI-SW versus IR-MI-SW-inhibitor [a,b,c,e]; (5) iron pretreament then shockwave [c]; and (6) shockwave BOLD [d]. Segment(Medviso) post-processing to derive EDV, ESV, SV, CO, EF, T2-maps and T2star-maps; and Image-Arena(Tomtec) to derive GLS, GCS, GRS and segmental-strains; (6)multi-colour-flow-cytometry CD45-CD90+ and CD45+CD34+ on PBMC after shockwave. In-vitro: (7) Shockwave-treated HCF, HVT, HUVEC, and cardiomyocytes qPCR-assessed for SDF1. (8) Shockwave or SDF1-spiking treatment on oxygen-deprived cardiomyocytes and assessed for viability. RESULTS: (1) Segmental-strains distinguished phenotypes of Healthy, AAR and Infarction; global-strains detected IR-MI better than EF. (2) Shockwave induced inotropy. (3) DPP4-inhibitor prolonged shockwave-inotropic effect. (4) Smaller infarction in shockwave group; reduced transmurality with DPP4-inhibitor; stronger GLS, GCS, GRS in IR-MI-SW than IR-MI; stronger GLS and GRS in IR-MI-SW-inhibitor had than IR-MI-SW while GCS was unchanged. (5) Shockwave reduced T2, signifying cell-homing. (6) Shockwave increased BOLD signifying angiogenesis. (7) SDF1 expression increased in HCF, HVT, HUVEC but not in cardiomyocytes. (8) Shockwave and SDF1-spiking improved cardiomyocytes viability. CLINICAL CONTEXT: Shockwave with DPP4-inhibitor treatment in reperfused-STEMI could limit infarct size and improve cardiac function.Open Acces

A Non-Rigid Registration Method for Analyzing Myocardial Wall Motion for Cardiac CT Images

Cardiac resynchronization therapy (CRT) has a high percentage of non-responders. Successfully locating the optimal location for CRT lead placement on a priori images can increase efficiency in procedural preparation and execution and could potentially increase the rate of CRT responders. Registration has been used in the past to assess the motion of medical images. Specifically, one method of non-rigid registration has been utilized to assess the motion of left ventricular MR cardiac images. As CT imaging is often performed as part of resynchronization treatment planning and is a fast and accessible means of imaging, extending this registration method to assessing left ventricular motion of CT images could provide another means of reproducible contractility assessment. This thesis investigates the use of non-rigid registration to evaluate the myocardium motion in multi-phase multi-slice computed tomography (MSCT) cardiac imaging for the evaluation of mechanical contraction of the left ventricle

Investigating left ventricular infarct extension after myocardial infarction using cardiac imaging and patient-specific modelling

Acute myocardial infarction (MI) is one of the leading causes of death worldwide that commonly affects the left ventricle (LV). Following MI, the LV mechanical loading is altered and may undergo a maladaptive compensatory mechanism that progressively leads to adverse LV remodelling and then heart failure. One of the remodelling processes is the infarct extension which involves necrosis of healthy myocardium in the border zone (BZ), progressively enlarging the infarct zone (IZ) and recruiting the remote zone (RZ) into the BZ. The mechanisms underlying infarct extension remain unclear, but myocyte stretching has been suggested as the most likely cause. A recent personalized LV modelling work found that infarct extension was correlated to inadequate diastolic fibre stretch and higher infarct stiffness. However, other possible factors of infarct extension may not have been elucidated in this work due to the limited number of myocardial locations analysed at the subendocardium only. Using human patient-specific left- ventricular (LV) models established from cardiac magnetic resonance imaging (MRI) of 6 MI patients, the correlation between infarct extension and regional mechanics impairment was studied. Prior to the modelling, a 2D-4D registration-cum-segmentation framework for the delineation of LV in late gadolinium enhanced (LGE) MRI was first developed, which is a pre-requisite for infarct scar quantification and localization in patient-specific 3D LV models. This framework automatically corrects for motion artifacts in multimodal MRI scans, resolving the issue of inaccurate infarct mapping and geometry reconstruction which is typically done manually in most patient-specific modelling work. The registration framework was evaluated against cardiac MRI data from 27 MI patients and showed high accuracy and robustness in delineating LV in LGE MRI of various quality and different myocardial features. This framework allows the integration of LV data from both LGE and cine scans and to facilitate the reconstruction of accurate 3D LV and infarct geometries for subsequent computational study. In the patient-specific LV mechanical modelling, the LV mechanics were formulated using a quasi-static and nearly incompressible hyperelastic material law with transversely isotropic behaviour. The patient-specific models were incorporated with realistic fibre orientation and excitable contracting myocardium. Optimisation of passive and active material parameters were done by minimizing the myocardial wall distance between the reference and end-diastole/end-systole LV geometries. Full cardiac cycle of the LV models was then simulated and stress/strain data were extracted to determine the correlation between regional mechanics abnormality and infarct extension. The fibre stress-strain loops (FSSLs) were analysed and its abnormality was characterized using the directional regional external work (DREW) index, which measures FSSL area and loop direction. Sensitivity studies were also performed to investigate the effect of infarct stiffness on regional myocardial mechanics and potential for infarct extension. It was found that infarct extension was correlated to severely abnormal FSSL in the form of counter-clockwise loop, as indicated by negative DREW values. In regions demonstrating negative DREW values, substantial isovolumic relaxation (IVR) fibre stretching was observed. Further analysis revealed that the occurrence of severely abnormal FSSL near the RZ-BZ boundary was due to a large amount of surrounding infarcted tissue that worsen with excessively stiff IZ