Advances in computational modelling for personalised medicine after myocardial infarction

Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners

A novel method for estimating myocardial strain: assessment of deformation tracking against reference magnetic resonance methods in healthy volunteers

We developed a novel method for tracking myocardial deformation using cardiac magnetic resonance (CMR) cine imaging. We hypothesised that circumferential strain using deformation-tracking has comparable diagnostic performance to a validated method (Displacement Encoding with Stimulated Echoes- DENSE) and potentially diagnostically superior to an established cine-strain method (feature-tracking). 81 healthy adults (44.6 ± 17.7 years old, 47% male), without any history of cardiovascular disease, underwent CMR at 1.5T including cine, DENSE, and late gadolinium enhancement in subjects >45 years. Acquisitions were divided into 6 segments, and global and segmental peak circumferential strain were derived and analysed by age and sex. Peak circumferential strain differed between the 3 groups (DENSE: -19.4 ± 4.8 %; deformation-tracking: -16.8 ± 2.4 %; feature-tracking: -28.7 ± 4.8%) (ANOVA with Tukey post-hoc, F-value 279.93, p<0.01). DENSE and deformation-tracking had better reproducibility than feature-tracking. Intra-class correlation co-efficient was >0.90. Larger magnitudes of strain were detected in women using deformation-tracking and DENSE, but not feature-tracking. Compared with a reference method (DENSE), deformation-tracking using cine imaging has similar diagnostic performance for circumferential strain assessment in healthy individuals. Deformation-tracking could potentially obviate the need for bespoke strain sequences, reducing scanning time and is more reproducible than feature-tracking

Estimating prognosis in patients with acute myocardial infarction using personalized computational heart models

Biomechanical computational models have potential prognostic utility in patients after an acute ST-segment–elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP < 130 mmHg). Cardiac MRI was performed in the patients (2 days & 6 months post-STEMI) and the volunteers, and biomechanical heart models were synthesized for each subject. The candidate parameters included normalized active tension (ATnorm) and active tension at the resting sarcomere length (Treq, reflecting required contractility). Myocardial contractility was inversely determined from personalized heart models by matching CMR-imaged LV dynamics. Compared with controls, patients with recent STEMI exhibited increased LV wall active tension when normalized by SBP. We observed a linear relationship between Treq 2 days post-MI and global longitudinal strain 6 months later (r = 0.86; p = 0.03). Treq may be associated with changes in LV function in the longer term in STEMI patients complicated by LV dysfunction. Further studies seem warranted

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

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

Myocardial tissue tagging with cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) is currently the gold standard for assessing both global and regional myocardial function. New tools for quantifying regional function have been recently developed to characterize early myocardial dysfunction in order to improve the identification and management of individuals at risk for heart failure. Of particular interest is CMR myocardial tagging, a non-invasive technique for assessing regional function that provides a detailed and comprehensive examination of intra-myocardial motion and deformation. Given the current advances in gradient technology, image reconstruction techniques, and data analysis algorithms, CMR myocardial tagging has become the reference modality for evaluating multidimensional strain evolution in the human heart. This review presents an in depth discussion on the current clinical applications of CMR myocardial tagging and the increasingly important role of this technique for assessing subclinical myocardial dysfunction in the setting of a wide variety of myocardial disease processes

Evaluation of left ventricle strains by applying SPAMM cardiac MRI techniques

Tese de mestrado integrado em Engenharia Biomédica e Biofísica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2017As doenças cardiovasculares são uma das maiores causas de morte no mundo, causando aproximadamente 17.5 milhões de mortes por ano, o que corresponde a 31% de todas as mortes no mundo. Estas doenças caracterizam-se pela diminuição da contração da parede do miocárdio durante o ciclo cardíaco. Uma das doenças mais comuns é a cardiomiopatia dilatada (DCM), onde o músculo cardíaco fica mais fino e fraco, e as cavidades cardíacas ficam aumentadas. Consequentemente, a capacidade de deformação do miocárdio é diminuída, o que impossibilita o coração de bombear eficientemente o sangue para as restantes partes do corpo. Esta condição é maioritariamente genética, mas também pode ser provocada por diferentes causas como infeções virais, inflamações ou lesões. A análise da deformação da parede do miocárdio aquando do ciclo cardíaco possibilita não só a identificação das deformações normais do miocárdio aquando da sua contração, mas também das deformações anormais devido a doenças cardíacas. A técnica de ressonância magnética cardíaca (CMR) é não invasiva e tem uma elevada resolução espacial, sendo por isso indispensável no estudo destas deformações. Esta técnica permite detetar essas mesmas características da contração e distensão do músculo cardíaco, possibilitando a análise das deformações e a respetiva distinção entre os pacientes saudáveis e os pacientes com cardiomiopatia dilatada. Nesta doença, observa-se o estreitamento das paredes do miocárdio e a dilatação das cavidades cardíacas, como é o caso do ventrículo esquerdo, o que se observa pelo aumento do seu diâmetro. O resultado é um decréscimo significativo na tensão e deformação da parede do miocárdio, o que impacta negativamente na eficiência da sístole ventricular. A técnica de Modulação Espacial da Magnetização (SPAMM) tem vindo a ser proposta para a visualização do movimento e deslocamento da parede do miocárdio no seu plano de imagem, através da criação de padrões de linhas e grelhas com magnetização alterada na imagem. Estes padrões são marcadores que seguem a deformação do músculo cardíaco. Ao serem detetados e seguidos durante o ciclo cardíaco, estes marcadores contribuem para o estudo do movimento da parede do miocárdio aquando da sua contração. A amostra usada nesta tese consistiu em imagens de ressonância magnética cardíaca de 9 indivíduos, 3 dos quais são saudáveis e os outros 6 são pacientes com DCM. As imagens foram adquiridas pelo Hospital Motol em Praga (República Checa) e analisadas pelo Instituto de Informática, Robótica and Cibernética da Faculdade de Engenharia Elétrica em Praga. A tese proposta teve como objetivo o estudo da deformação radial no ventrículo esquerdo através da automatização na deteção dos marcadores presentes no mesmo, assim como no seu seguimento ao longo do ciclo cardíaco. Pela análise das deformações de voluntários saudáveis e de pacientes com cardiomiopatia dilatada, é possível comparar os seus padrões de deformação cardíaca de modo a analisar as diferenças entre os dois. Pelo estudo das deformações, sabe-se que um valor positivo de deformação corresponde a um espessamento de um objeto e um valor negativo corresponde ao seu encurtamento, relativamente ao seu tamanho inicial. Durante a contração do miocárdio, é normal observar-se um espessamento e encurtamento da parede do ventrículo esquerdo. Assim sendo, as deformações radiais tomam valores positivos devido ao espessamento da parede e as circunferenciais tomam valores negativos devido ao encurtamento da parede. Os métodos de deteção dos marcadores foram aplicados com sucesso nos sujeitos saudáveis e com cardiomiopatia dilatada, sendo que estes marcadores foram também corretamente seguidos ao longo do ciclo cardíaco, durante a sístole e a diástole. Nos sujeitos saudáveis, foi observado um intervalo de deformações radiais entre 18.63 % e 43.84 %, enquanto que em pacientes com cardiomiopatia dilatada, os valores de deformação radial variaram entre 10.73 % e 14.14 %. De notar que os valores das deformações radiais são positivos e, por isso, confirmam o espessamento da parede do ventrículo esquerdo aquando da sua contração. Assim sendo, os resultados desta dissertação vão de encontro com os resultados dos testes feitos anteriormente em voluntários saudáveis e com cardiomiopatia dilatada, visto que os intervalos de deformações são semelhantes para os dois grupos. Ao comparar-se as deformações dos dois grupos pelo teste estatístico Mann-Whitney, verificou-se uma diferença significativa (p<0.05) nos valores das deformações entre os mesmos. Assim sendo, esta tese também confirma que os pacientes com a doença cardíaca têm valores mais baixos de deformação em relação aos indivíduos saudáveis, tal como é comprovado pelo facto da doença cardiomiopatia dilatada ser caracterizada pela diminuição da deformação do miocárdio durante o ciclo cardíaco. Pela comparação dos diferentes segmentos ao longo das secções básica, média e apical do ventrículo esquerdo, foi também observado que nos pacientes com cardiomiopatia dilatada, a deformação mínima correspondeu ao segmento inferolateral da base do ventrículo e que a deformação máxima se deu no segmento anteroseptal da secção média do ventrículo. Em contrapartida, nos indivíduos saudáveis, o mínimo da deformação foi no segmento anterior e o máximo da deformação correspondeu ao segmento inferoseptal, ambos os segmentos pertencentes à secção média do ventrículo esquerdo. Estes resultados foram também observados em estudos anteriores relativos a pacientes com cardiomiopatia dilatada. Relativamente à análise das deformações circunferenciais, foi observado que, nos sujeitos saudáveis, o intervalo das deformações esteve entre -32.17 % e -24.33 %, enquanto que nos pacientes com cardiomiopatia dilatada, o intervalo foi de -15.92 % a -8.17 %. O valor negativo da deformação circunferencial é devido ao encurtamento da parede do ventrículo esquerdo, sendo que este valor se encontra em conformidade com o correto comportamento da parede do ventrículo durante a contração do miocárdio, tal como observado em estudos anteriores. Para alem destes factos, também se verificou que o máximo da deformação circunferencial foi dado na secção media do ventrículo esquerdo, enquanto que o mínimo foi na secção apical do mesmo. Ao comparar-se as deformações circunferenciais, pelo teste estatístico Mann-Whitney, durante a systole e entre os dois grupos de sujeitos, verificou-se existe uma diminuição significativa (p<0.05) do seu valor absoluto nos pacientes, relativamente aos sujeitos saudáveis. Adicionalmente, também foi estudado o efeito do género (masculino / feminino) nas deformações dos pacientes com cardiomiopatia dilatada. Os resultados do estudo mostraram que as deformações do ventrículo esquerdo são maiores no género masculino, em relação ao género feminino. Contudo, outros estudos realizados anteriormente não relataram qualquer relação entre as deformações do miocárdio e o género (masculino / feminino) dos respetivos pacientes. Com esta dissertação foi possível concluir que o estudo das deformações no ventrículo esquerdo é um parâmetro importante na avaliação da contratilidade do coração. O facto de a Ressonância magnética ser uma técnica não invasiva e da técnica de Modulação espacial da magnetização permitir criar um padrão de grelha que facilmente acompanha movimentos na parede do músculo, possibilitou a eficiente deteção das deformações na parede do ventrículo esquerdo. Uma outra conclusão importante deste estudo é o facto da doença cardiomiopatia dilatada provocar uma diminuição da capacidade de deformação do coração, visto que a doença é caracterizada pelo estreitamento da parede do miocardio e por uma dilatação das cavidades cardíacas, especialmente dos ventrículos. Este facto está na origem da diminuição das deformações radiais e circunferenciais, em relação às deformações dos pacientes saudáveis. Foi também observado que a secção do ventrículo esquerdo responsável pela maior deformação é a secção média, pois foi nesta secção que se observou um maior número de valores máximos de deformação. Por fim, nesta tese também se confirma que durante a contração do miocárdio, a deformação radial teve valores positivos e a deformação circunferencial teve valores negativos, o que comprova que houve um espessamento e encurtamento da parede do ventrículo esquerdo durante a sua contração. Assim sendo, verifica-se que ao longo desta dissertação foi possível analisar a relação da deformação do ventrículo esquerdo com a doença cardiomiopatia dilatada e consequentemente, avaliar se a deformação calculada é normal ou devido à doença cardíaca. Como tal, a partir deste estudo foi possível facilitar a deteção das deformações, bem como fazer a sua análise para contribuição do estudo das doenças cardíacas, tal como a cardiomiopatia dilatada. Como trabalho futuro, poderá estudar-se como detetar automaticamente o ventrículo esquerdo e como calcular eficientemente as suas deformações. Assim, poderá também aprofundar-se o estudo e a análise da doença cardiomiopatia dilatada e de outras doenças cardíacas.Cardiovascular diseases are one of the main causes of death in the world. These diseases modify the myocardial wall contraction during cardiac cycle. One of the most common types of these diseases is the dilated cardiomyopathy (DCM), in which the heart muscle becomes weaker and the heart cavities are enlarged. Consequently, the heart deformation capability is decreased, which prevents it from pumping blood efficiently. This condition can be genetic or due to various causes such as viral infections, inflammation or injuries. The analysis of cardiac wall deformation enables identifying normal or abnormal deformations due to heart disease. Cardiac Magnetic Resonance Imaging (MRI) is able to detect the characteristic abnormalities of DCM, which are the wall thinning and dilation of heart chambers, more specifically the increasing of ventricle diameter. The result is a significant decrease in wall stress and strain, which has a negative impact on systolic ventricular performance. The Spatial Modulation of Magnetization (SPAMM) technique has been proposed for imaging myocardial motion within the plane of the image by creating a pattern of lines or grids with altered magnetization on the image. These patterns are tags that deform according to the heart muscle deformation and can be detected and tracked for wall motion studying. The sample used in this thesis was composed by cardiac MRI scans of 9 subjects, 3 of which were healthy subjects and the other 6 were patients with DCM. The scans were acquired by Motol Hospital in Prague (Czech Republic) and analyzed in the Institute of Informatics, Robotics and Cybernetics from the Faculty of Electrical Engineering in Prague. The proposed thesis intended to assess the left ventricle (LV) radial and circumferential strains by automatically detecting LV tags and tracking those during cardiac cycle. By analyzing the heart strains from healthy subjects and patients with DCM, it is possible to compare both patterns of cardiac deformation within the cardiac cycle in order to analyze the differences between them. Positive strain values describe myocardial thickening and negative values describe its shortening, related to its original length. During myocardial contraction, the radial strain is positive due to myocardial thickening, and the circumferential strain is negative due to myocardial shortening. The tracking methods were successfully applied on heathy and DCM patients and the tags were successfully detected during systole and diastole. A comparison between the strains, by Mann-Whitney statistical test, during the cardiac cycle in both sets of subjects, identified a significant difference (p<0.05) between them. It was observed that in healthy subjects, the radial strain varied from 18.63 % to 43.84 %, while in DCM patients, the radial strain varied from 10.73 % to 14.14 %. The radial strains are positive values, as the LV thickens during myocardial contraction. The results of this thesis are in agreement with previous studies done with DCM and healthy subjects, as the ranges of deformations are similar in both sets of subjects. Moreover, this thesis also confirms that DCM patients have lower radial strain values than healthy subjects, as DCM is characterized by a decrease in heart muscle strain during the cardiac cycle. By comparing several segments in the different sections of the heart, it was also observed that in DCM patients, the minimum deformation was on the inferolateral segment of the base, while the maximum was on the anteroseptal segment of the middle section. However, in healthy subjects, the minimum deformation was on the anterior segment and the maximum was on the inferoseptal segment, both in the middle section of the left ventricle. This result was also observed in previous studies. Regarding to the circumferential strains analysis, it was observed that in healthy subjects, the average circumferential strain range was from -32.17 % to -24.33 %, while in DCM patients, it was from -15.92 % to -8.17 %. The negative value of the circumferential strain means that there was a LV wall shortening and this is in conformity with the correct behavior of LV during myocardial contraction. Moreover, in healthy subjects, the mid section of LV has the major strain, while in DCM patients, it is the apical section. A comparison between the circumferential strains during systole in both sets of subjects supports the previous studies results, in which the circumferential stains values are negative during systole. Additionally, the results of Mann-Whitney statistical test also shown significant lower absolute (p<0.05) values on DCM patients, when comparing to healthy subjects. Additionally, the effect of the gender (male/ female) on the strains was also investigated on the DCM patients and the results suggest that in women, the LV strain is lower than in men. Despite these results, the other studies did not report any conclusion related to this effect. It is possible to state that the study of the LV strain is an important parameter in the evaluation of the cardiac contractility. A non-invasive assessment of LV by MRI and the superimposed grid created by SPAMM improved the tracking of LV wall strains. Another important conclusion of this study was that DCM decreases the deformation capabilities of the heart, as it is responsible for the wall thinning and dilation of heart chambers, causing a decrease in wall radial and circumferential strains. Moreover, it was observed that the major section responsible for the myocardial deformation was the middle section of the LV. Finally, this thesis also confirmed that during myocardial contraction, the radial strain values are positive due to the myocardial thickening and the circumferential values are negative due to the myocardial shortening. A need to automatically detect the LV and also to efficiently calculate the LV strains in a short time can be developed as a future work, which will also improve the analysis of DCM disease and other cardiac diseases

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