Visualization of Minute Mechanical-Excitation/Relaxation Wave-front Propagation in Myocardial Tissue

Unlike the case of skeletal muscle, the direction of myocardial contraction does not coincide with the direction of work necessary to eject the intraventricular blood, contributing to great complexity of the wall deformation sequence of cardiac contraction. The advent of advanced techniques (CT^1^, MRI^2,3^, SPECT^4^, echocardiology^5-9^, electrocardiography^10^, and magnetocardiography^11,12^) has enabled to the evaluation of cardiac function and disorders by the measurement of blood flow, pressure, electrical reaction process, and other factors. However, complexity of the contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured based on these electro-magnetic phenomena. Here, developing and using a noninvasive novel imaging modality with high temporal and spatial resolutions^13-17^, we show that the propagation of the mechanical wave-front occurs at the beginning of each cardiac contraction and relaxation sequence for the first time. The former occurs about 60 ms prior to the ordinarily accepted onset time of the contraction (R-wave of the electrocardiogram). From the apical side of the interventricular septum, close to the terminal of the Purkinje fibers (specialized to carry contraction impulses), a minute velocity component with an amplitude of several tenth micrometers is generated and propagates sequentially to the entire left ventricle, that is, it propagates from the apex to the base of the posterior wall, and then from the base to the apex of the septum, with a propagation speed of 3-9 m/s. The latter occurs at the end of the first heart sound at the apical side and propagates to the base side with a speed of 0.6 m/s. These physiological findings, unlike the widely accepted myocardial excitation process, have potential for accurate assessment of myocardial tissue damage in coronary disease and cardiomyopathy. This dynamic measurement modality is also applicable to various tissues in biology

Myocardial strain in healthy adults across a broad age range as revealed by cardiac magnetic resonance imaging at 1.5 and 3.0T: associations of myocardial strain with myocardial region, age, and sex

Purpose: We assessed myocardial strain using cine displacement encoding with stimulated echoes (DENSE) using 1.5T and 3.0T MRI in healthy adults. Materials and Methods: Healthy adults without any history of cardiovascular disease underwent MRI at 1.5T and 3.0T within 2 days. The MRI protocol included b-SSFP, 2D cine-EPI-DENSE, and late gadolinium enhancement in subjects>45 years. Acquisitions were divided into 6 segments, global and segmental peak longitudinal and circumferential strain were derived and analyzed by field strength, age and gender. Results: 89 volunteers (mean age 44.8 ± 18.0 years, range: 18-87 years) underwent MRI at 1.5T, and 88 of these subjects underwent MRI at 3.0T (1.4±1.4 days between the scans). Compared with 3.0T, the magnitudes of global circumferential (-19.5±2.6% vs. -18.47±2.6%; p=0.001) and longitudinal (-12.47±3.2% vs -10.53±3.1%; p=0.004) strain were greater at 1.5T. At 1.5T, longitudinal strain was greater in females than in males: -10.17±3.4% vs. -13.67±2.4%; p=0.001. Similar observations occurred for circumferential strain at 1.5T (-18.72±2.2% vs. -20.10±2.7%; p=0.014) and at 3.0T (-17.92 ± 1.8% vs -19.1 ± 3.1%; p=0.047). At 1.5T, longitudinal and circumferential strain were not associated with age after accounting for sex (longitudinal strain p= 0.178, circumferential strain p= 0.733). At 3.0T, longitudinal and circumferential strain were associated with age. (p<0.05) Longitudinal strain values were greater in the apico-septal, basal-lateral and mid-lateral segments and circumferential strain in the inferior, infero-lateral and antero-lateral LV segments. Conclusion: Myocardial strain parameters as revealed by cine-DENSE at different MRI field strengths were associated with myocardial region, age and sex

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

Analytical method to measure three-dimensional strain patterns in the left ventricle from single slice displacement data

Background: Displacement encoded Cardiovascular MR (CMR) can provide high spatial resolution measurements of three-dimensional (3D) Lagrangian displacement. Spatial gradients of the Lagrangian displacement field are used to measure regional myocardial strain. In general, adjacent parallel slices are needed in order to calculate the spatial gradient in the through-slice direction. This necessitates the acquisition of additional data and prolongs the scan time. The goal of this study is to define an analytic solution that supports the reconstruction of the out-of-plane components of the Lagrangian strain tensor in addition to the in-plane components from a single-slice displacement CMR dataset with high spatio-temporal resolution. The technique assumes incompressibility of the myocardium as a physical constraint. Results: The feasibility of the method is demonstrated in a healthy human subject and the results are compared to those of other studies. The proposed method was validated with simulated data and strain estimates from experimentally measured DENSE data, which were compared to the strain calculation from a conventional two-slice acquisition. Conclusion: This analytical method reduces the need to acquire data from adjacent slices when calculating regional Lagrangian strains and can effectively reduce the long scan time by a factor of two

A Left Ventricular Motion Phantom for Cardiac Magnetic Resonance Imaging

The mammalian left ventricle (LV) has two distinct motion patterns: wall thickening and rotation. The purpose of this study was to design and build a low-cost, non-ferromagnetic LV motion phantom, for use with cardiac magnetic resonance imaging (MRI), that is able to produce physiologically realistic LV wall thickening and rotation. Cardiac MRI is continuously expanding its range of techniques with new pulse sequences, including new tissue tagging techniques which allow intra-myocardial deformation to be visualized. An essential step in the development of new cardiac MRI techniques is validating their performance in the presence of motion. MRI-compatible dynamic motion phantoms are of substantial benefit in the development of cardiac specific-magnetic resonance imaging techniques. These phantoms enable the investigation of motion effects images by mimicking the three dimensional motion of the heart. To date, no single study has succeeded in duplicating both LV motion patterns, in an MRI-compatible cardiac motion phantom. In addition, a phantom that is 100 MRI-compatible with low cost to build would be desirable to researchers. We have built two MRI-compatible phantoms, housed within a common enclosure and each filled with MRI-visible dielectric gel (as a surrogate to myocardium),which model the wall thickening and rotation motions of the left ventricle independently. The wall motion phantom is pneumatic, driven by a custom non-ferromagnetic pump which cyclically fills and empties a latex balloon within the phantom. The rotation phantom is manually driven by a plastic actuator which rotates the phantom through a specified angular rotation. Each phantom also generates a TTL pulse for triggering the MRI scanner. Although this circuitry contains ferromagnetic materials, it can be located outside the scanner bore. The wall thickening motion phantom has been tested using segmented cine, real time cine and grid tagged MRI acquisition sequences. Results were significant with 4 average variability and physiologically

A Left Ventricular Motion Phantom for Cardiac Magnetic Resonance Imaging

The mammalian left ventricle (LV) has two distinct motion patterns: wall thickening and rotation. The purpose of this study was to design and build a low-cost, non-ferromagnetic LV motion phantom, for use with cardiac magnetic resonance imaging (MRI), that is able to produce physiologically realistic LV wall thickening and rotation. Cardiac MRI is continuously expanding its range of techniques with new pulse sequences, including new tissue tagging techniques which allow intra-myocardial deformation to be visualized. An essential step in the development of new cardiac MRI techniques is validating their performance in the presence of motion. MRI-compatible dynamic motion phantoms are of substantial benefit in the development of cardiac specific-magnetic resonance imaging techniques. These phantoms enable the investigation of motion effects images by mimicking the three dimensional motion of the heart. To date, no single study has succeeded in duplicating both LV motion patterns, in an MRI-compatible cardiac motion phantom. In addition, a phantom that is 100 MRI-compatible with low cost to build would be desirable to researchers. We have built two MRI-compatible phantoms, housed within a common enclosure and each filled with MRI-visible dielectric gel (as a surrogate to myocardium),which model the wall thickening and rotation motions of the left ventricle independently. The wall motion phantom is pneumatic, driven by a custom non-ferromagnetic pump which cyclically fills and empties a latex balloon within the phantom. The rotation phantom is manually driven by a plastic actuator which rotates the phantom through a specified angular rotation. Each phantom also generates a TTL pulse for triggering the MRI scanner. Although this circuitry contains ferromagnetic materials, it can be located outside the scanner bore. The wall thickening motion phantom has been tested using segmented cine, real time cine and grid tagged MRI acquisition sequences. Results were significant with 4 average variability and physiologically

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

A Left Ventricular Motion Phantom for Cardiac Magnetic Resonance Imaging

The mammalian left ventricle (LV) has two distinct motion patterns: wall thickening and rotation. The purpose of this study was to design and build a low-cost, non-ferromagnetic LV motion phantom, for use with cardiac magnetic resonance imaging (MRI), that is able to produce physiologically realistic LV wall thickening and rotation. Cardiac MRI is continuously expanding its range of techniques with new pulse sequences, including new tissue tagging techniques which allow intra-myocardial deformation to be visualized. An essential step in the development of new cardiac MRI techniques is validating their performance in the presence of motion. MRI-compatible dynamic motion phantoms are of substantial benefit in the development of cardiac specific-magnetic resonance imaging techniques. These phantoms enable the investigation of motion effects images by mimicking the three dimensional motion of the heart. To date, no single study has succeeded in duplicating both LV motion patterns, in an MRI-compatible cardiac motion phantom. In addition, a phantom that is 100 MRI-compatible with low cost to build would be desirable to researchers. We have built two MRI-compatible phantoms, housed within a common enclosure and each filled with MRI-visible dielectric gel (as a surrogate to myocardium),which model the wall thickening and rotation motions of the left ventricle independently. The wall motion phantom is pneumatic, driven by a custom non-ferromagnetic pump which cyclically fills and empties a latex balloon within the phantom. The rotation phantom is manually driven by a plastic actuator which rotates the phantom through a specified angular rotation. Each phantom also generates a TTL pulse for triggering the MRI scanner. Although this circuitry contains ferromagnetic materials, it can be located outside the scanner bore. The wall thickening motion phantom has been tested using segmented cine, real time cine and grid tagged MRI acquisition sequences. Results were significant with 4 average variability and physiologically