MR imaging of left-ventricular function : novel image acquisition and analysis techniques.

Many cardiac diseases, such as myocardial ischemia, secondary to coronary artery disease, may be identified and localized through the analysis of cardiac deformations. Early efforts for quantifying ventricular wall motion used surgical implantation and tracking of radiopaque markers with X-ray imaging in canine hearts [1]. Such techniques are invasive and affect the regional motion pattern of the ventricular wall during the marker tracking process and, clearly are not feasible clinically. Noninvasive imaging techniques are vital and have been widely applied to the clinic. MRI is a noninvasive imaging technique with the capability to monitor and assess the progression of cardiovascular diseases (CVD) so that effective procedures for the care and treatment of patients can be developed by physicians and researchers. It is capable of providing 3D analysis of global and regional cardiac function with great accuracy and reproducibility. In the past few years, numerous efforts have been devoted to cardiac motion recovery and deformation analysis from MR imaging sequences. In order to assess cardiac function, there are two categories of indices that are used: global and regional indices. Global indices include ejection fraction, cavity volume, and myocardial mass [2]. They are important indices for cardiac disease diagnosis. However, these global indices are not specific for regional analysis. A quantitative assessment of regional parameters may prove beneficial for the diagnosis of disease and evaluation of severity and the quantification of treatment [3]. Local measures, such as wall deformation and strain in all regions of the heart, can provide objective regional quantification of ventricular wall function and relate to the location and extent of ischemic injury. This dissertation is concerned with the development of novel MR imaging techniques and image postprocessing algorithms to analyze left ventricular deformations. A novel pulse sequence, termed Orthogonal CSPAMM (OCSPAMM), has been proposed which results in the same acquisition time as SPAMM for 2D deformation estimation while keeping the main advantages of CSPAMM [4,5]: i.e., maintaining tag contrast through-out the ECG cycle. Different from CSPAMM, in OCSPAMM the second tagging pulse orientation is rotated 90 degrees relative to the first one so that motion information can be obtained simultaneously in two directions. This reduces the acquisition time by a factor of two as compared to the traditional CSPAMM, in which two separate imaging sequences are applied per acquisition. With the application of OCSPAMM, the effect of tag fading encountered in SPAMM tagging due to Tl relaxation is mitigated and tag deformations can be visualized for the entire cardiac cycle, including diastolic phases. A multilevel B-spline fitting method (MBS) has been proposed which incorporates phase-based displacement information for accurate calculation of 2D motion and strain from tagged MRI [6, 7]. The proposed method combines the advantages of continuity and smoothness of MBS, and makes use of phase information derived from tagged MR images. Compared to previous 2D B-spline-based deformation analysis methods, MBS has the following advantages: 1) It can simultaneously achieve a smooth deformation while accurately approximating the given data set; 2) Computationally, it is very fast; and 3) It can produce more accurate deformation results. Since the tag intersections (intersections between two tag lines) can be extracted accurately and are more or less distributed evenly over the myocardium, MBS has proven effective for 2D cardiac motion tracking. To derive phase-based displacements, 2D HARP and SinMod analysis techniques [8,9] were employed. By producing virtual tags from HARP /SinMod and calculating intersections of virtual tag lines, more data points are obtained. In the reference frame, virtual tag lines are the isoparametric curves of an undeformed 2D B-spline model. In subsequent frames, the locations of intersections of virtual tag lines over the myocardium are updated with phase-based displacement. The advantage of the technique is that in acquiring denser myocardial displacements, it uses both real and virtual tag line intersections. It is fast and more accurate than 2D HARP and SinMod tracking. A novel 3D sine wave modeling (3D SinMod) approach for automatic analysis of 3D cardiac deformations has been proposed [10]. An accelerated 3D complementary spatial modulation of magnetization (CSPAMM) tagging technique [11] was used to acquire complete 3D+t tagged MR data sets of the whole heart (3 dynamic CSPAMM tagged MRI volume with tags in different orientations), in-vivo, in 54 heart beats and within 3 breath-holds. In 3D SinMod, the intensity distribution around each pixel is modeled as a cosine wave front. The principle behind 3D SinMod tracking is that both phase and frequency for each voxel are determined directly from the frequency analysis and the displacement is calculated from the quotient of phase difference and local frequency. The deformation fields clearly demonstrate longitudinal shortening during systole. The contraction of the LV base towards the apex as well as the torsional motion between basal and apical slices is clearly observable from the displacements. 3D SinMod can automatically process the image data to derive measures of motion, deformations, and strains between consecutive pair of tagged volumes in 17 seconds. Therefore, comprehensive 4D imaging and postprocessing for determination of ventricular function is now possible in under 10 minutes. For validation of 3D SinMod, 7 3D+t CSPAMM data sets of healthy subjects have been processed. Comparison of mid-wall contour deformations and circumferential shortening results by 3D SinMod showed good agreement with those by 3D HARP. Tag lines tracked by the proposed technique were also compared with manually delineated ones. The average errors calculated for the systolic phase of the cardiac cycles were in the sub-pixel range

Cardiac motion and deformation estimation in tagged magnetic resonance imaging

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Electrónica Médica)Cardiovascular diseases are the main cause of death in Europe, with an estimate of 4.3 million deaths each year. The assessment of the regional wall deformation is a relevant clinical indicator, and can be used to detect several cardiac lesions. Nowadays, this study can be performed using several image modalities. In the current thesis, we focus on tagged Magnetic Resonance imaging (t-MRI) technique. Such technique allows acquiring images with tags on the myocardium, which deform with the muscle. The present thesis intends to assess the left ventricle (LV) deformation using radial and circumferential strain. To compute such strain values, both endo- and epicardial contours of the LV are required. As such, a new framework to automatically assess the LV function is proposed. This framework presents: (i) an automatic segmentation technique, based on a tag suppression strategy followed by an active contour segmentation method, and (ii) a tracking approach to extract myocardial deformation, based on a non-rigid registration method. The automatic segmentation uses the B-spline Explicit Active Surface framework, which was previously applied in ultra-sound and cine-MRI images. In both cases, a real-time and accurate contour was achieved. Regarding the registration step, starting from a state-of-art approach, termed sequential 2D, we suggest a new method (termed sequential 2D+t), where the temporal information is included on the model. The tracking methods were first tested on synthetic data to study the registration parameters influence. Furthermore, the proposed and original methods were applied on porcine data with myocardial ischemia. Both methods were able to detect dysfunctional regions. A comparison between the strain curve in the sequential 2D and sequential 2D+t strategies was also shown. As conclusion, a smoothing effect in the strain curve was detected in the sequential 2D+t strategy. The validation of the segmentation approach uses a human dataset. A comparison between the manual contour and the proposed segmentation method results was performed. The results, suggest that proposed method has an acceptable performance, removing the tedious task related with manual segmentation and the intra-observer variability. Finally, a comparison between the proposed framework and the currently available commercial software was performed. The commercial software results were obtained from core-lab analysis. An acceptable result (r = 0.601) was achieved when comparing the strain peak values. Importantly, the proposed framework appears to present a more acceptable result.As doenças cardiovasculares são a principal causa de morte na Europa, com aproximadamente 4.7 milhões de mortes por ano. A avaliação da deformação do miocárdio a um nível local é um importante indicador clínico e pode ser usado para a deteção de lesões cardíacas. Este estudo é normalmente realizado usando várias modalidades de imagem médica. Nesta tese, a Resonância Magnética (RM) marcada foi a técnica selecionada. Estas imagens têm marcadores no músculo cardíaco, os quais se deformam com o miocárdio e podem ser usados para o estudo da deformação cardíaca. Nesta tese, pretende-se estudar a deformação radial e circunferencial do ventrículo esquerdo (VE). Assim, um contorno do endo- e epicárdio no VE é essencial. Desta forma, uma ferramenta para o estudo da deformação do VE foi desenvolvida. Esta possui: (i) um método de segmentação automático, usando uma estratégia de supressão dos marcadores, seguido de uma segmentação c um contorno ativo, e (ii) um método de tracking para determinação da deformação cardíaca, baseado em registo não rígido. A segmentação automática utiliza a ferramenta B-spline Explicit Active Surface, que foi previamente aplicada em imagens de ultrassons e cine-RM. Em ambos os casos, uma segmentação em tempo real e com elevada exatidão foi alcançada. Vários esquemas de registo foram apresentados. Neste ponto, começando com uma técnica do estado da arte (designada de sequencial 2D), uma nova metodologia foi proposta (sequencial 2D+t), onde a informação temporal é incorporada no modelo. De forma a analisar a influência dos parâmetros do registo, estes foram estudados num dataset sintético. De seguida, os diferentes esquemas de registo foram testados num dataset suíno com isquemia. Ambos os métodos foram capazes de detetar as regiões disfuncionais. De igual forma, utilizando as curvas de deformação obtidas para cada um dos métodos propostos, foi possível observar uma suavização na direção temporal para o método sequencial 2D+t. Relativamente à segmentação, esta foi validada com um dataset humano. Um contorno manual foi comparado com o obtido pelo método proposto. Os resultados sugerem que a nova estratégia é aceitável, sendo mais rápida do que a realização de um contorno manual e eliminando a variabilidade entre observadores. Por fim, realizou-se uma comparação entre a ferramenta proposta e um software comercial (com análise de core-lab). A comparação entre os valores de pico da deformação exibe uma correlação plausível (r=0.601). Contudo, é importante notar, que a nova ferramenta tende a apresentar um resultado mais aceitável

Growth, modelling and remodelling of cardiac tissue: a multiphase approach

Rheumatic heart disease (RHD) is identified as a serious health concern in developing countries, specifically amongst young individuals, accounting for between 250 000 and 1.4 million deaths annually. As such, the attention of this research is initially placed on the importance of the development of a cardiac analysis toolbox with functionality for pathophysiological analysis of the disease. Subsequently, in order to further the understanding of the mechanisms of the disease as linked to cardiomyocyte growth and remodelling of the microstructure, a continuum bi-phasic model applicable to cardiac tissue is formulated based on the theory of porous media (TPM). This makes it possible to account for interactions and contributions of multiple phases of constituent materials, which in computational cardiac modelling are the solid phase - the cardiac tissue - and the liquid phase - blood and interstitial uid. Subsequent attention is paid to the cardiac model development in order to implement a sound base on which to add strain-driven phase transition via a mass supply function proposed within this study. To this end, based on thermodynamical restrictions, constitutive relations are proposed for stress, permeability, seepage velocity, mass supply and interaction forces such as friction. The approach is implemented in the in-house computational cardiac mechanics toolbox SESKA which supports finite element as well as Element- free Galerkin-based approximations. This investigation considers the passive and active non-linear elastic material behaviour of the myocardium of the left ventricle coupled with porous media theory, along with an an additional coupling to the haemodynamics of the circulatory system, facilitating modelling of the full cardiac cycle. As such, an initial cardiac growth and remodelling computer model is developed as an initial step to computational modelling of the adverse effects of RHD and other similar in ammatory heart diseases, with the potential to limit the invasiveness and risk of in-vivo patient studies. A patient specific case study is conducted, making use of cardiovascular magnetic resonance scans taken over a period of two years from a patient affected by RHD to generate realistic 3D computer models, from which information is drawn with regards to the pathophysiological behaviour of the disease

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

Non-rigid medical image registration with extended free form deformations: modelling general tissue transitions

Image registration seeks pointwise correspondences between the same or analogous objects in different images. Conventional registration methods generally impose continuity and smoothness throughout the image. However, there are cases in which the deformations may involve discontinuities. In general, the discontinuities can be of different types, depending on the physical properties of the tissue transitions involved and boundary conditions. For instance, in the respiratory motion the lungs slide along the thoracic cage following the tangential direction of their interface. In the normal direction, however, the lungs and the thoracic cage are constrained to be always in contact but they have different material properties producing different compression or expansion rates. In the literature, there is no generic method, which handles different types of discontinuities and considers their directional dependence. The aim of this thesis is to develop a general registration framework that is able to correctly model different types of tissue transitions with a general formalism. This has led to the development of the eXtended Free Form Deformation (XFFD) registration method. XFFD borrows the concept of the interpolation method from the eXtended Finite Element method (XFEM) to incorporate discontinuities by enriching B-spline basis functions, coupled with extra degrees of freedom. XFFD can handle different types of discontinuities and encodes their directional-dependence without any additional constraints. XFFD has been evaluated on digital phantoms, publicly available 3D liver and lung CT images. The experiments show that XFFD improves on previous methods and that it is important to employ the correct model that corresponds to the discontinuity type involved at the tissue transition. The effect of using incorrect models is more evident in the strain, which measures mechanical properties of the tissues

3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

Intervertebral Disc Structure and Mechanical Function Under Physiological Loading Quantified Non-invasively Utilizing MRI and Image Registration

The intervertebral discs (IVD) functions to permit motion, distribute load, and dissipate energy in the spine. It performs these functions through its heterogeneous structural organization and biochemical composition consisting of several tissue substructures: the central gelatinous nucleus pulposus (NP), the surrounding fiber reinforced layered annulus fibrosus (AF), and the cartilaginous endplates (CEP) that are positioned between the NP and vertebral endplates. Each tissue contributes individually to overall disc mechanics and by interacting with adjacent tissues. Disruption of the disc\u27s tissues through aging, degeneration, or tear will not only alter the affected tissue mechanical properties, but also the mechanical behavior of adjacent tissues and, ultimately, overall disc segment function. Thus, there is a need to measure disc tissue and segment mechanics in the intact disc so that interactions between substructures are not disrupted. Such measurements would be valuable to study mechanisms of disc function and degeneration, and develop and evaluate surgical procedures and therapeutic implants. The objectives of this study were to develop, validate, and apply methods to visualize and quantify IVD substructure geometry and track internal deformations for intact human discs under axial compression. The CEP and AF were visualized through MRI parameter mapping and image sequence optimization for ideal contrast. High-resolution images enabled geometric measurements. Axial compression was performed using a custom-built loading device that permitted long relaxation times outside of the MRI, 300 m isotropic resolution images were acquired, and image registration methods applied to measure 3D internal strain. In conclusion, new methods to visualize and quantify CEP thickness, annular tear detection and geometric quantification, and non-invasively measure 3D internal disc strains were established. No correlation was found between CEP thickness and disc level; however the periphery was significantly thicker compared to central locations. Clear distinction of adjacent AF lamellae enabled annular tear detection and detailed geometric quantification. Annular tears demonstrated non-classic geometry through interconnecting radial, circumferential, and perinuclear formations. Regional strain inhomogeneity was observed qualitatively and quantitatively. Variation in strain magnitudes might be explained by geometry in axial and circumferential strain while peak radial strain in the posterior AF may have important implications for disc herniation