Myocardial strain analysis with high temporal resolution MRI tagging: extended 3D motion tracking in normal and LBBB hearts

Tese de doutoramento em Biofísica, apresentada à Universidade de Lisboa através da Faculdade de Ciências, 200

Relation between torsion and cross-sectional area change in the human left ventricle

During the ejection phase, motion of the left ventricular (LV) wall is such that all myocardial fibers shorten to the same extent. In a mathematical model of LV mechanisms it was found that this condition could be satisfied only if torsion around the long axis followed a unique function of the ratio of cavity volume to wall volume. When fiber shortening becomes non-uniform due to cardiac pathology, this pathology may be reflected in aberration of the torsional motion pattern. In the present study we investigated whether the predicted regular motion pattern could be found in nine healthy volunteers, using Magnetic Resonance Tagging. In two parallel short-axis cross-sections, displacement, rotation, and area ejection were derived from the motion of tags, attached non-invasively to the myocardium. Information from both sections was combined to determine area ejection, quantified as the change in the logarithm of the ratio of cavity area to wall area, and torsion, represented by the shear angle on the epicardium. Linear regression was applied to torsion as a function of area ejection. The slope thus found (-0.173 +/- 0.024 rad, mean +/- S.D.) was similar to the slope as predicted by the model of LV mechanics (-0.194 +/- 0.026 rad). In conclusion, the relation between area ejection and torsion could be assessed noninvasively in humans. In healthy volunteers, the relation was close to what was predicted by a mathematical model of LV mechanics, and also close to what was found earlier in experiments on animals. [Journal Article; In English; United States

Doctor of Philosophy

dissertationImage-based biomechanics, particularly numerical modeling using subject-specific data obtained via imaging, has proven useful for elucidating several biomechanical processes, such as prediction of deformation due to external loads, applicable to both normal function and pathophysiology of various organs. As the field evolves towards applications that stretch the limits of imaging hardware and acquisition time, the information traditionally expected as input for numerical routines often becomes incomplete or ambiguous, and requires specific acquisition and processing strategies to ensure physical accuracy and compatibility with predictive mathematical modeling. These strategies, often derivatives or specializations of traditional mechanics, effectively extend the nominal capability of medical imaging hardware providing subject-specific information coupled with the option of using the results for predictive numerical simulations. This research deals with the development of tools for extracting mechanical measurements from a finite set of imaging data and finite element analysis in the context of constructing structural atlases of the heart, understanding the biomechanics of the venous vasculature, and right ventricular failure. The tools include: (1) application of Hyperelastic Warping image registration to displacement-encoded MRI for reconstructing absolute displacement fields, (2) combination of imaging and a material parameter identification approach to measure morphology, deformation, and mechanical properties of vascular tissue, and (3) extrapolation of diffusion tensor MRI acquired at a single time point for the prediction the structural changes across the cardiac cycle with mechanical simulations. Selected tools were then applied to evaluate structural changes in a reversible animal model for right ventricular failure due to pressure overload

COMPUTATIONAL INVESTIGATION OF TRANSMURAL DIFFERENCES IN LEFT VENTRICULAR CONTRACTILITY AND HYDROGEL INJECTION TREATMENT FOR MYOCARDIAL INFARCTION

Heart failure (HF) is one of the leading causes of death and impacts millions of people throughout the world. Recently, injectable hydrogels have been developed as a potential new therapy to treat myocardium infarction (MI). This dissertation is focused on two main topics: 1) to gain a better understanding the transmural contractility in the healthy left ventricle (LV) wall and 2) investigate the efficacy of the hydrogel injection treatment on LV wall stress and function. The results indicate that a non-uniform distribution of myocardial contractility in the LV wall provide a better representation of normal LV function. The other important study explored the influence altering the stiffness of the biomaterial hydrogel injections. These results show that a larger volume and higher stiffness injection reduce myofiber stress the most and maintaining the wall thickness during loading. The computational approach developed in this dissertation could be used in the future to evaluate the optimal properties of the hydrogel. The last study used a combination of MRI, catheterization, finite element (FE) modeling to investigate the effects of hydrogel injection on borderzone (BZ) contractility after MI. The results indicate that the treatment with hydrogel injection significantly improved BZ function and reduce LV remodeling, via altered MI properties. Additionally, the wall thickness in the infarct and BZ regions were significantly higher in the treated case. Conclusion: hydrogel injection could be a valuable clinical therapy for treating MI

QUANTIFICATION OF MYOCARDIAL MECHANICS IN LEFT VENTRICLES UNDER INOTROPIC STIMULATION AND IN HEALTHY RIGHT VENTRICLES USING 3D DENSE CMR

Statistical data from clinical studies indicate that the death rate caused by heart disease has decreased due to an increased use of evidence-based medical therapies. This includes the use of magnetic resonance imaging (MRI), which is one of the most common non-invasive approaches in evidence-based health care research. In the current work, I present 3D Lagrangian strains and torsion in the left ventricle of healthy and isoproterenol-stimulated rats, which were investigated using Displacement ENcoding with Stimulated Echoes (DENSE) cardiac magnetic resonance (CMR) imaging. With the implementation of the 12-segment model, a detailed profile of regional cardiac mechanics was reconstructed for each subject. Statistical analysis revealed that isoproterenol induced a significant change in the strains and torsion in certain regions at the mid-ventricle level. In addition, I investigated right ventricular cardiac mechanics with the methodologies developed for the left ventricle. This included a comparison of different regions within the basal and mid-ventricular regions. Despite no regional variation found in the peak circumferential strain, the peak longitudinal strain exhibited regional variation at the anterior side of the RV due to the differences in biventricular torsion, mechanism of RV free wall contraction, and fiber architecture at RV insertions. Future applications of the experimental work presented here include the construction and validation of biventricular finite element models. Specifically, the strains predicted by the models will be statistically compared with experimental strains. In addition, the results of the present study provide an essential reference of RV baseline evaluated with DENSE MRI, a highly objective technique

Motion tracking tMRI datasets to quantify abnormal left ventricle motion using finite element modelling

According to `The Atlas of Heart Disease and Stroke'[MMMG04] published by the World Health Organization, heart disease accounts for nearly half the deaths in both the developed and developing countries and is the world's single biggest killer. However, early detection of a diseased heart condition can prevent many of these fatalities. Regional wall motion abnormalities of the heart precede both ECG abnormalities and chest pain as an indicator of myocardial ischaemia and are an excellent indicator of coronary stenosis [GZM97]. These motion abnormalities of the heart muscle are difficult to observe and track, because the heart is a relatively smooth organ with few landmarks and non-rigid motion with a twisting motion or tangential component. The MRI tissue-tagging technique gives researchers the first glimpse into how the heart actually beats. This research uses the tagged MRI images of the heart to create a three dimensional model of a beating heart indicating the stress of a region. Tagged MRI techniques are still developing and vary vastly, meaning that there needs to be a methodology that can adapt to these changes rapidly and effectively, to meet the needs of the evolving technology. The focus of this research is to develop and test such a methodology by the means of a Strain Estimation Pipeline along with an effective way of validating any changes made to the individual processes that it comprises of

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

Novel cardiovascular magnetic resonance phenotyping of the myocardium

INTRODUCTION Left ventricular (LV) microstructure is unique, composed of a winding helical pattern of myocytes and rotating aggregations of myocytes called sheetlets. Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease characterised by left ventricular hypertrophy (LVH), however the link between LVH and underlying microstructural aberration is poorly understood. In vivo cardiovascular diffusion tensor imaging (cDTI) is a novel cardiovascular MRI (CMR) technique, capable of characterising LV microstructural dynamics non-invasively. In vivo cDTI may therefore improve our understanding microstructural-functional relationships in health and disease. METHODS AND RESULTS The monopolar diffusion weighted stimulated echo acquisition mode (DW-STEAM) sequence was evaluated for in vivo cDTI acquisitions at 3Tesla, in healthy volunteers (HV), patients with hypertensive LVH, and HCM patients. Results were contextualised in relation to extensively explored technical limitations. cDTI parameters demonstrated good intra-centre reproducibility in HCM, and good inter-centre reproducibility in HV. In all subjects, cDTI was able to depict the winding helical pattern of myocyte orientation known from histology, and the transmural rate of change in myocyte orientation was dependent on LV size and thickness. In HV, comparison of cDTI parameters between systole and diastole revealed an increase in transmural gradient, combined with a significant re-orientation of sheetlet angle. In contrast, in HCM, myocyte gradient increased between phases, however sheetlet angulation retained a systolic-like orientation in both phases. Combined analysis with hypertensive patients revealed a proportional decrease in sheetlet mobility with increasing LVH. CONCLUSION In vivo DW-STEAM cDTI can characterise LV microstructural dynamics non-invasively. The transmural rate of change in myocyte angulation is dependent on LV size and wall thickness, however inter phase changes in myocyte orientation are unaffected by LVH. In contrast, sheetlet dynamics demonstrate increasing dysfunction, in proportion to the degree of LVH. Resolving technical limitations is key to advancing this technique, and improving the understanding of the role of microstructural abnormalities in cardiovascular disease expression.Open Acces

Myocardial strain, torsion and untwisting in the normal and failing heart measured with magnetic resonance imaging

Rossum, A.C. van [Promotor]Heethaar, R.M. [Promotor]Marcus, J.T. [Copromotor]Götte, M.J.W. [Copromotor

A Novel Composite Material-based Computational Model for Left Ventricle Biomechanics Simulation

To model cardiac mechanics effectively, various mechanical characteristics of cardiac muscle tissue including anisotropy, hyperelasticity, and tissue active contraction characteristics must be considered. Some of these features cannot be implemented using commercial finite element (FE) solvers unless additional custom-developed computer codes/subroutines are appended. Such codes/subroutines are unavailable for the research community. Accordingly, the overarching objective of this research is to develop a novel LV mechanics model which is implementable in commercial FE solvers and can be used effectively within inverse FE frameworks towards cardiac disease diagnosis and therapy. This was broken down into a number of objectives. The first objective is to develop a novel cardiac tissue mechanical model. This model was constructed of microstructural cardiac tissue constituents while their associated volume contributions and mechanical properties were incorporated into the model. These constituents were organized in small FE tissue specimen models consistent with the normal/pathological cardiac tissue microstructure. In silico biaxial/uniaxial mechanical tests were conducted on the specimen models and corresponding stress-strain data were validated by comparing them with cardiac tissue data reported in the literature. Another objective of this research is developing a novel FE-based mechanical model of the LV which is fully implementable using commercial FE solvers without requiring further coding, potentially leading to a computationally efficient model which is easily adaptable to diverse pathological conditions. This was achieved through considering a novel composite material model of the cardiac tissue while all aspects of the cardiac mechanics including hyperelasticity, anisotropy, and active tissue responses were preserved. The model was applied to an in silico geometry of a canine LV under both normal and pathological conditions and systolic/diastolic responses of the model were compared with corresponding data of other LV mechanical models and LV contraction measurements. To test the suitability of the proposed cardiac model for FE inversion-based algorithms, the model was utilized for LV diastolic mechanical simulation to estimate the tissue stiffness and blood pressure using an ad-hoc optimization scheme. This led to reasonable tissue stiffness and blood pressure values falling within the range of LV measurements of healthy subjects, confirming the efficacy of this model for inversion-based diagnosis applications