Estudio tractográfico de la anatomía helicoidal del miocardio ventricular mediante resonancia magnética por tensor de difusión / Helical structure of the cardiac ventricular anatomy assessed by diffusion tensor magnetic resonance imaging with multiresolution tractography

Introducción y objetivos. La integración de la anatomía y la función del miocardio ventricular es fundamental para una completa comprensión de la fisiología cardiaca, lo que podría revelar conocimientos clave para futuros estudios experimentales y procedimientos clínicos. Se han propuesto varios modelos conceptuales de la organización de las fibras miocárdicas, pero la dificultad para automatizar y analizar objetivamente una estructura anatómica tan compleja ha impedido que se llegue a un acuerdo. El objetivo de nuestro estudio es analizar objetivamente la arquitectura de las fibras miocárdicas mediante métodos avanzados de procesamiento gráfico por computadora aplicados a imágenes de resonancia magnética por tensor de difusión. Métodos. Se han realizado reconstrucciones tractográficas automatizadas de datos de imágenes de resonancia magnética por tensor de difusión sin segmentar de corazones provenientes de la base de datos pública de la Johns Hopkins University. Las reconstrucciones a máxima resolución se han construido con 200 semillas y se componen de perfiles calculados sobre el volumen de vectores propios primarios obtenidos del tensor de difusión. También aportamos una nueva técnica de visualización multiescalar para obtener tractografías simplificadas. Esta metodología permite mantener las principales propiedades geométricas de las fibras y descifrar las principales propiedades de la organización arquitectónica del miocardio. Resultados. En el análisis de las tractografías de todo el espectro multiescalar, encontramos una correlación exacta en los detalles de bajo nivel, así como de la conceptualización abstracta de la disposición helicoidal continua de las fibras miocárdicas que conforman la arquitectura ventricular. Conclusiones. El análisis objetivo de la arquitectura miocárdica mediante un método automatizado que incluye el miocardio completo y utiliza diferentes niveles de complejidad tridimensional revela una organización de las fibras en forma de estructura helicoidal continua que conforma ambos ventrículos. Estos datos concuerdan con el modelo de banda ventricular miocárdica descrita por F. Torrent-Guasp (AU)

Introduction and objectives. Deeper understanding of the myocardial structure linking the morphology and function of the heart would unravel crucial knowledge for medical and surgical clinical procedures and studies. Several conceptual models of myocardial fiber organization have been proposed but the lack of an automatic and objective methodology prevented an agreement. We sought to deepen this knowledge through advanced computer graphical representations of the myocardial fiber architecture by diffusion tensor magnetic resonance imaging. Methods. We performed automatic tractography reconstruction of unsegmented diffusion tensor magnetic resonance imaging datasets of canine heart from the public database of the Johns Hopkins University. Full-scale tractographies have been built with 200 seeds and are composed by streamlines computed on the vector field of primary eigenvectors at the diffusion tensor volumes. We also introduced a novel multiscale visualization technique in order to obtain a simplified tractography. This methodology retains the main geometric features of the fiber tracts, making it easier to decipher the main properties of the architectural organization of the heart. Results. Output analysis of our tractographic representations showed exact correlation with low-level details of myocardial architecture, but also with the more abstract conceptualization of a continuous helical ventricular myocardial fiber array. Conclusions. Objective analysis of myocardial architecture by an automated method, including the entire myocardium and using several 3-dimensional levels of complexity, reveals a continuous helical myocardial fiber arrangement of both right and left ventricles, supporting the anatomical model of the helical ventricular myocardial band described by F. Torrent-Guasp (AU)

Helical structure of the cardiac ventricular anatomy assessed by diffusion tensor magnetic resonance imaging with multiresolution tractography.

INTRODUCTION AND OBJECTIVES: Deeper understanding of the myocardial structure linking the morphology and function of the heart would unravel crucial knowledge for medical and surgical clinical procedures and studies. Several conceptual models of myocardial fiber organization have been proposed but the lack of an automatic and objective methodology prevented an agreement. We sought to deepen this knowledge through advanced computer graphical representations of the myocardial fiber architecture by diffusion tensor magnetic resonance imaging. METHODS: We performed automatic tractography reconstruction of unsegmented diffusion tensor magnetic resonance imaging datasets of canine heart from the public database of the Johns Hopkins University. Full-scale tractographies have been built with 200 seeds and are composed by streamlines computed on the vector field of primary eigenvectors at the diffusion tensor volumes. We also introduced a novel multiscale visualization technique in order to obtain a simplified tractography. This methodology retains the main geometric features of the fiber tracts, making it easier to decipher the main properties of the architectural organization of the heart. RESULTS: Output analysis of our tractographic representations showed exact correlation with low-level details of myocardial architecture, but also with the more abstract conceptualization of a continuous helical ventricular myocardial fiber array. CONCLUSIONS: Objective analysis of myocardial architecture by an automated method, including the entire myocardium and using several 3-dimensional levels of complexity, reveals a continuous helical myocardial fiber arrangement of both right and left ventricles, supporting the anatomical model of the helical ventricular myocardial band described by F. Torrent-Guasp.

Left ventricular torsion and longitudinal shortening: two fundamental components of myocardial mechanics assessed by tagged cine-MRI in normal subjects.

Cardiac magnetic resonance imaging (Cardiac MRI) has become a gold standard diagnostic technique for the assessment of cardiac mechanics, allowing the non-invasive calculation of left ventricular long axis longitudinal shortening (LVLS) and absolute myocardial torsion (AMT) between basal and apical left ventricular slices, a movement directly related to the helicoidal anatomic disposition of the myocardial fibers. The aim of this study is to determine AMT and LVLS behaviour and normal values from a group of healthy subjects. A group of 21 healthy volunteers (15 males) (age: 23-55 y.o., mean: 30.7 ± 7.5) were prospectively included in an observational study by cardiac MRI. Left ventricular rotation (degrees) was calculated by custom-made software (Harmonic Phase Flow) in consecutive LV short axis planes tagged cine-MRI sequences. AMT was determined from the difference between basal and apical planes LV rotations. LVLS (%) was determined from the LV longitudinal and horizontal axis cine-MRI images. All the 21 cases studied were interpretable, although in three cases the value of the LV apical rotation could not be determined. The mean rotation of the basal and apical planes at end-systole were -3.71° ± 0.84° and 6.73° ± 1.69° (n:18) respectively, resulting in a LV mean AMT of 10.48° ± 1.63° (n:18). End-systolic mean LVLS was 19.07 ± 2.71%. Cardiac MRI allows for the calculation of AMT and LVLS, fundamental functional components of the ventricular twist mechanics conditioned, in turn, by the anatomical helical layout of the myocardial fibers. These values provide complementary information about systolic ventricular function in relation to the traditional parameters used in daily practice.

The myocardial band.

Francisco (Paco) Torrent-Guasp, a Spanish cardiologist working in De'nia, Alicante, discovered that the complex structure of the ventricular myocardium is due to a double-loop helical orientation of a single muscular band that extends from the pulmonary artery to the aorta, with a 180-degree twist in its middle part. He predicted the twist-untwist motion of the ventricles and suggested that this is due to agonist-antagonist mechanics of the ventricular band segments.

Switch from caspase-dependent to caspase-independent death during heart development: essential role of endonuclease G in ischemia-induced DNA processing of differentiated cardiomyocytes.

Differentiated cardiomyocytes are resistant to caspase-dependent cell death; however, the mechanisms involved are still uncertain. We previously reported that low Apaf1 expression partially accounts for cardiomyocyte resistance to apoptosis. Here, we extend the knowledge on the molecular basis of cardiac resistance to caspase activation by showing that the whole caspase-dependent pathway is silenced during heart development. Experimental ischemia triggers caspase activation in embryonic cardiomyocytes and proliferating fibroblasts, but not in neonatal and adult cardiomyocytes. Ischemia induces the release of the proapoptotic factors cytochrome c, truncated-AIF, and EndoG from mitochondria in postnatal cardiomyocytes in the absence of caspase activation. On the one hand, lentiviral-driven knockdown of EndoG shows that this gene is essential for ischemia-induced DNA degradation in neonatal cardiomyocytes, but not in proliferating fibroblasts; on the other hand, the AIF gene is essential for high molecular DNA cleavage in fibroblasts, but not in postmitotic cardiomyocytes, where it plays a prosurvival role during reoxygenation. These results show the switch from caspase-dependent to caspase-independent death pathways after cardiac cell differentiation, and disclose the relevance of EndoG in the caspase-independent DNA processing of differentiated cardiomyocytes.

Morphological and functional evidences of the helical heart from non-invasive cardiac imaging.

The non-invasive study of cardiac mechanics has been improved after the recent introduction of advanced magnetic resonance and echocardiographic imaging techniques. Tagged and diffusion-sensitive cardiac magnetic resonance allows the study of myocardial torsion dynamics as well as the anatomical disposition of myocardial fibers. Local myocardial strain and synchronicity of myocardial contraction can also be determined with Doppler tissue imaging (DTI) echocardiography. Published results with these techniques demonstrate a mechanical behavior that is a consequence of a myocardial helical fiber orientation and strongly support the evidence of the double-loop single muscular band model described by Torrent-Guasp.

Bcl-2 is a key factor for cardiac fibroblast resistance to programmed cell death.

Cardiac fibroblasts play an essential role in the physiology of the heart. These produce extracellular matrix proteins and synthesize angiogenic and cardioprotective factors. Although fibroblasts of cardiac origin are known to be resistant to apoptosis and to remain metabolically active in situations compromising cell survival, the underlying mechanisms are unknown. Here, we report that cardiac fibroblasts were more resistant than dermal or pulmonary fibroblasts to mitochondria-dependent cell death. Cytochrome c release was blocked in cardiac fibroblasts but not in dermal fibroblasts treated with staurosporine, etoposide, serum deprivation, or simulated ischemia, precluding caspase-3 activation and DNA fragmentation. Resistance to apoptosis of cardiac fibroblasts correlated with the expression of the anti-apoptotic protein Bcl-2, whereas skin and lung fibroblasts did not express detectable levels of this protein. Bcl-x(L,) Bax, and Bak were expressed at similar levels in cardiac, dermal, and lung fibroblasts. In addition, the death of cardiac fibroblasts during hypoxia was not associated with the cleavage of Bid but rather with Bcl-2 disappearance, suggesting the requirement of the mitochondrial apoptotic machinery to execute death receptor-induced programmed cell death. Knockdown of bcl-2 expression by siRNA in cardiac fibroblasts increased their apoptotic response to staurosporine, serum, and glucose deprivation and to simulated ischemia. Moreover, dermal fibroblasts overexpressing Bcl-2 achieved a similar level of resistance to these stimuli as cardiac fibroblasts. Thus, our data demonstrate that Bcl-2 is an important effector of heart fibroblast resistance to apoptosis and highlight a probable mechanism for promoting survival advantage in fibroblasts of cardiac origin.

Role of noninvasive antimyosin imaging in infants and children with clinically suspected myocarditis.

UNLABELLED: Endomyocardial biopsy is an invasive procedure, often performed on children for the diagnosis of myocarditis, and is not without risk. Therefore, a noninvasive test of adequate diagnostic accuracy is highly desirable. We evaluated the role of antimyosin scintigraphy in infants and children with clinically suspected myocarditis. METHODS: Forty patients (age range, 2 mo to 14 y) with suspected myocarditis underwent (111)In-antimyosin scintigraphy. All patients were clinically followed for 29 +/- 17 mo; 21 patients underwent serial antimyosin scans (3.8 +/- 1.7 per patient). The antimyosin uptake was assessed by heart-to-lung ratio (HLR). The scan results were compared with endomyocardial biopsy results in 22 patients. RESULTS: Thirty-five of the 40 patients showed abnormal antimyosin findings; 17 patients showed intense myocardial antimyosin uptake (HLR > 2). The HLR was higher in patients presenting within the first 2 mo of illness (2.09 +/- 0.43 vs. 1.74 +/- 0.34, P = 0.01). Of 22 patients with endomyocardial biopsy, 17 demonstrated myocarditis. All 9 patients who had an HLR > 2 and underwent endomyocardial biopsy had histologic evidence of myocarditis. Of the remaining 13 patients with HLR < 2, 8 had biopsy-verified myocarditis (62%). The intensity of antimyosin uptake was the major determinant of survival in children, with a relative risk of 18 (confidence interval, 1.34-242; P = 0.027). High antimyosin uptake (HLR > 2) seen within 2 mo of the onset of symptoms was associated with a higher mortality rate. The survivors with an HLR > 2 and those with an HLR < 2 showed a high likelihood of complete functional recovery. Furthermore, the patients with serial antimyosin scans having persistently positive findings showed a poor clinical outcome. CONCLUSION: Intense myocardial uptake of antimyosin antibody is a reliable indicator of myocarditis in infants and children. Severe myocardial damage detected in the early phase of disease is associated with a higher mortality rate. The persistence of antimyosin uptake is associated with poor clinical outcomes.

[Imported hookworm infection in African immigrants in Spain: study of 285 patients]. / Uncinariasis importada por inmigrantes africanos: estudio de 285 casos.

BACKGROUND AND OBJECTIVE: Hookworm infection is a worldwide intestinal parasitic disease affecting more than one billion people. It represents an important public health problem in rural areas of developing countries. In our environment, it is generally considered an imported disease due to the immigration process. PATIENTS AND METHOD: Retrospective observational study of African immigrants diagnosed with hookworm infection at the Immigration and Tropical Medicine Unit of the Hospital of Mataró over the period 1984-1999. RESULTS: We identified 285 patients, mainly young males, from Gambia or Senegal, with a precarious job who had arrived in Spain 3 years earlier or less. Abdominal pain was the commonest reason for consultation (28.8%) cases. Non digestive symptoms were 35.6% and 4.6% remained assymptomatic. 60% had a concomitant infectious disease. Laboratory tests showed iron-deficiency anemia in 28.4% and eosinophilia in 52.3%. 70% of patients did not come to visit after treatment. CONCLUSIONS: Microbiologic stool examination is recommended as part of the health assessment of immigrants from countries where hookworm infection is highly prevalent, even in the absence of abdominal symptoms or abnormalities of the red and white blood series.

Uncinariasis importada por inmigrantes africanos:estudio de 285 casos / Imported hookworm infection in African immigrants in Spain: Study of 285 patients

FUNDAMENTO Y OBJETIVO: La uncinariasis es una parasitosis intestinal de amplia distribución mundial que afecta a más de mil millones de personas. Constituye un importante problema de salud pública en áreas rurales de los países con baja renta. En España es una enfermedad generalmente importada y, dado el fenómeno inmigratorio progresivo, conviene valorar su impacto. PACIENTES Y MÉTODO: Estudio observacional retrospectivo en una población de inmigrantes africanos diagnosticados de uncinariasis en la Unidad de Medicina de la Inmigración y Tropical del Hospital de Mataró, durante el período 1984-1999. RESULTADOS: Se diagnosticaron 285 pacientes, mayoritariamente varones, jóvenes, originarios de Gambia o Senegal, con inestabilidad laboral y con 3 o menos años de migración. Los motivos de consulta fueron variados. Entre los 10 más frecuentes el dolor abdominal fue el primero (28,8 por ciento), los síntomas no digestivos representaron el 35,6 por ciento y los pacientes asintomáticos supusieron el 4,6 por ciento. El 60 por ciento presentaba otras enfermedades infecciosas asociadas. En el estudio analítico se detectó anemia ferropénica en el 28,4 por ciento y eosinofilia en el 52,3 por ciento. Hubo un 70 por ciento de pérdidas en la visita de control postratamiento. CONCLUSIONES: Es recomendable realizar un análisis microbiológico de heces en los inmigrantes procedentes de países con alta prevalencia de uncinariasis, aunque no presenten sintomatología digestiva o alteración del hemograma (AU)

Coronary endothelial dysfunction and myocardial cell damage in chronic stable idiopathic dilated cardiomyopathy.

UNLABELLED: Impairment of endothelium-dependent vasodilatation in response to acetylcholine reflects an abnormal endothelial function. Labelled indium-111 monoclonal antimyosin antibodies enable detection of myocardial cell damage. We analysed whether endothelial dysfunction correlates with myocardial antimyosin uptake in a selected group of patients with idiopathic dilated cardiomyopathy. METHODS: Twenty-two consecutive patients with chronic stable idiopathic dilated cardiomyopathy (18 males and four females) were included. The duration of heart failure symptoms was 46+/-34 months. At inclusion, the functional class of New York Heart Association was 2.1+/-0.7. Endothelial function was evaluated using intracoronary graded concentrations of acetylcholine. Vasomotor responses of the left anterior descending coronary artery were measured by quantitative coronary analysis. Myocardial uptake of antimyosin antibodies was quantified by means of a heart-to-lung ratio (HLR). RESULTS: Eighteen patients showed endothelial dysfunction (82%) and the remaining four patients showed a normal endothelial function. There were no statistically significant differences between patients with and without endothelial dysfunction in relation to clinical, echocardiographic and hemodynamic parameters. In addition, these variables did not correlate with the magnitude of the vasomotor response to acetylcholine. Eighteen patients (82%) showed abnormal antimyosin uptake; 15 of them (83%) showed endothelial dysfunction. The global mean HLR of antimyosin uptake was 1.73+/-0.24. The coronary vasomotor response to acetylcholine correlated with the intensity of uptake of antimyosin antibodies (r=-0.45, P<0.04). CONCLUSIONS: Coronary endothelial dysfunction and myocardial antimyosin uptake was found in a high percentage of patients with chronic stable idiopathic dilated cardiomyopathy. The abnormal vasomotor response seems to be related to the degree of myocardial damage.