How are the cardiomyocytes aggregated together within the walls of the left ventricular cone?

The manner of packing together of the cardiomyocytes within the walls of the cardiac ventricles has now been investigated for over half a millennium. In 1669, Lower dissected the ventricular mass, likening the arrangement to skeletal musculature, in the form of a myocardial band extending between the right and left atrioventricular junctions. Pettigrew subsequently showed obvious helical arrangements to be evident within the ventricular walls, but emphasised that the cardiomyocytes were attached to each other, and could not justifiably be compared with skeletal cardiomyocytes. Torrent-Guasp then reactivated the notion that the ventricular mass was formed of a solitary band. Unlike Lower, he dissected the band as extending between the pulmonary to the aortic roots. Multiple investigations conducted using gross dissection and histology, and more recently diffusion tensor magnetic resonance imaging and computed tomographic analysis, have shown an absence of any anatomical boundaries within the walls that might permit the mass uniformly to be dissected so as to reveal the band. A response to a recent letter to the Journal, nonetheless, claimed that the dissections had been validated by clinicians interpreting the findings so as to provide an explanation for ventricular cardiodynamics, arguing that the findings provided a suitable anatomical model for this purpose. Anatomical models, however, are of no value unless they are anatomically correct. In this review, therefore, we summarise the evidence showing that the cardiomyocytes making up the ventricular walls, rather than forming a ventricular myocardial band, are instead aggregated together to form a three-dimensional myocardial mesh.

Basic elements of nuclear magnetic resonance for use in medical diagnostics: magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS).

Magnetic resonance imaging (MRI) has established itself as a major imaging modality in life science research and clinical practice. It is characterized by high spatial resolution, high soft tissue contrast, non-invasiveness, and universal applicability in terms of orientation and location of imaging areas. The procedure allows furthermore the investigation of physiological and pathophysiological processes, in particular in combination with magnetic resonance spectroscopy (MRS). MR methodology is not exhausted, new procedures and areas of application develop widely in life science and medicine. This article is limited to basic physical aspects.

Ultrasound imaging and Doppler flow velocity measurement.

High frequency ultrasound (2-8 MHz typically) has established itself as a major medical imaging method associated with a wide range of clinical applications. Advantages include real-time applicability, lower cost compared with other medical imaging technologies, possibility of measuring blood flow velocities and desk-top instrumentation. Disadvantage is associated with lower image quality than is obtained with x-ray or magnetic resonance methods.

V.1. Ultrasound imaging and Doppler flow velocity measurement.

High frequency ultrasound (2 - 8 MHz typically) has established itself as a major medical imaging method associated with a wide range of clinical applications. Advantages include real-time applicability, lower cost compared with other medical imaging technologies, possibility of measuring blood flow velocities and desk-top instrumentation. Disadvantage is associated with lower image quality than is obtained with x-ray or magnetic resonance methods.

V.2. X-ray-based medical imaging: X-ray projection technique, image subtraction method, direct digital X-ray imaging, computed tomography (CT).

X-ray projection imaging, introduced in the early 20th century, was for a long time the only and still is a major routine diagnostic procedure that can be performed on the intact human body. With the advent of Computed Tomography in 1973, for the first time, a true 3D imaging of anatomical structures became feasible. Besides, digital recording and processing allowed further developments such as subtraction angiography in real-time or direct x-ray imaging without wet photographic methods.

V.3. Basic elements of nuclear magnetic resonance for use in medical diagnostics: Magnetic Resonance Imaging (MRI), magnetic resonance spectroscopy (MRS).

Magnetic Resonance Imaging (MRI) has established itself as a major imaging modality in life science research and clinical practice. It is characterized by high spatial resolution, high soft tissue contrast, non-invasiveness, and universal applicability in terms of orientation and location of imaging areas. The procedure allows furthermore the investigation of physiological and pathophysiological processes, in particular in combination with magnetic resonance spectroscopy (MRS). MR methodology is not exhausted, new procedures and areas of application develop widely in life science and medicine. This article is limited to basic physical aspects.

The architecture of the left ventricular myocytes relative to left ventricular systolic function.

OBJECTIVE: Mural thickening, combined with longitudinal and circumferential shortening, and apical along with basal twisting are critical components of the left ventricular systolic deformation that contribute to ventricular ejection. It is axiomatic that the spatial alignment of the actively contracting aggregates of myocytes must play a major role in the resulting ventricular deformation. The need to conserve functional global myocytic architecture, therefore, is an important aspect of the surgical manoeuvres affecting ventricular mass and geometry. To investigate the influence of the global alignment of the myocytes on ventricular contraction, we used a mathematical model simulating the large deformations produced by systolic contraction of the left ventricle of a human heart. METHODS: The alignment and meshing of the myocytes within their supporting fibrous matrix cause mechanical anisotropy, which was included in the mathematical model in the form of a unit vector field, constructed from the measured trajectories of aggregated myocytes in an autopsied human heart. The relationship between ventricular structure and ventricular dynamics was assessed by analysing the influence of systematic deviations of the orientation of the myocytes from their original alignment, in longitudinal as well as radial directions, on the distribution of stress and strain within the myocardium, as well as on the ejection fraction. In addition, simplified idealised geometries were used to investigate the influence of the overall geometrical modifications. RESULTS: Left ventricular function proved to be robust with respect to small-to-moderate rotational variations in myocytic alignment, up to 14 degrees , a finding which we attribute to an equalising effect of the non-uniform anisotropic pattern found in a real heart involving substantial local irregularities in the architecture of the aggregated myocytes. Severe deterioration of function occurred only when deviations in alignment exceeded 30 degrees . CONCLUSIONS: Our findings substantiate the concept of the myocardial walls representing a continuous three-dimensional meshwork, with the absence of any intermediate structures such as discrete bands or tracts extending over the ventricles, which could be destroyed surgically, thereby adversely affecting systolic function. With appropriate indications, they also support the validity of the surgical procedures performed to reduce ventricular radius and therefore to reduce mural stress.

Mathematical foundations of biomechanics.

The aim of biomechanics is the analysis of the structure and function of humans, animals, and plants by means of the methods of mechanics. Its foundations are in particular embedded in mathematics, physics, and informatics. Due to the inherent multidisciplinary character deriving from its aim, biomechanics has numerous connections and overlapping areas with biology, biochemistry, physiology, and pathophysiology, along with clinical medicine, so its range is enormously wide. This treatise is mainly meant to serve as an introduction and overview for readers and students who intend to acquire a basic understanding of the mathematical principles and mechanics that constitute the foundation of biomechanics; accordingly, its contents are limited to basic theoretical principles of general validity and long-range significance. Selected examples are included that are representative for the problems treated in biomechanics. Although ultimate mathematical generality is not in the foreground, an attempt is made to derive the theory from basic principles. A concise and systematic formulation is thereby intended with the aim that the reader is provided with a working knowledge. It is assumed that he or she is familiar with the principles of calculus, vector analysis, and linear algebra.

Imaging of tissue structures and mechanical analysis.

The anatomical structure of biological tissues and their mechanical function are closely related. Forces have a decisive influence on growth and remodeling of tissues; furthermore, intra- and extravascular transport processes are mostly controlled mechanically and the metabolism of many cells is influenced by flow-induced shear stresses. In order to facilitate a mechanical analysis of biological systems, the anatomical tissue structure has to be determined with the aid of 3D imaging methods. In particular, the anisotropic fibrous architecture of the organs involved along with appropriate constitutive relations have to be considered. Examples of structure-(mechanical) function relationships are discussed in an exemplary fashion for bone, the heart and the uterus. The behavior of biological structures under unphysiological loading situations, such as they may occur in accidents, is addressed.

An analysis of the spatial arrangement of the myocardial aggregates making up the wall of the left ventricle.

OBJECTIVE: We used the technique of peeling of myocardial aggregates, usually described as 'fibres', to determine the spatial arrangement of the myocytes in the left ventricular wall of a healthy autopsied human heart. METHODS: We digitised the left ventricular outer and inner boundaries, as well as the pathways in space, of almost 3000 aggregates harvested from the left ventricular myocardium. During the process of gradual peeling, we sought to identify the myocardial aggregates as uniformly as possible. Despite this, interpolation was necessary to complete the pattern so as to construct a unit vector field that represented the preferred direction of the myocardial aggregates throughout the entirety of the walls of the left ventricle of this individual human heart. RESULTS: Apart from the overall systematic arrangement of the aggregates necessary to achieve physiologic ventricular contraction, we documented substantial local heterogeneities in the orientation of the myocardial aggregates. In particular, a significant proportion of aggregates was found to intrude obliquely with respect to the ventricular boundaries, with markedly heterogeneous distribution. Moreover, the distribution of the helical angle of the aggregates relative to the ventricular base varied notably throughout the left ventricular free walls and the septum. Within the generally quite uniform and continuous structure of the ventricular mass, we were, however, unable to identify any organised tracts or functional subunits such as a 'helical ventricular band', nor did we find radial fibrous lamellas coursing across the ventricular wall. CONCLUSION: We suggest that the impact of local anatomical inhomogeneities, associated with gradients in regional contractile function on global ventricular dynamics, has been systematically underestimated in the past. Our analysis confirms furthermore the continuous nature of the myocardium associated with an overall gross organisation of the fibre direction field; however, there is no evidence of substructures compartmentalising the ventricles.

Ventricular myocardial architecture as visualised in postmortem swine hearts using magnetic resonance diffusion tensor imaging.

OBJECTIVE: The three-dimensional arrangement of the ventricular myocardial architecture remains controversial, in part because histological assessment is difficult to achieve, while anatomic dissections are, of necessity, destructive. In this study, we describe how the use of magnetic resonance diffusion tensor imaging has permitted us to reconstruct with precision the architecture of the ventricular myocardial fibres in the post-mortem swine heart. METHODS AND RESULTS: We obtained diffusion-weighted spin-echo measurements of autopsied porcine hearts using a whole body MR system. We calculated the diffusion tensor and the corresponding eigenvectors on a voxel-by-voxel basis. This permitted us to colour code the fibres, and reconstruct them by connecting voxels in direction of the largest eigenvector. Such reconstructions show that, in the middle layer of the left ventricle, most of the fibres have a circular orientation, albeit that a far from negligible component runs in a transverse direction. With increasing distance from the epicardium, the orientation of the fibres shows a continuous change in angulation with respect to an axis normal to the epicardium. CONCLUSION: Our data presented here supports the concept that the ventricular mass is arranged as a complex three-dimensional mesh of tangential and intruding fibres. The data offers no support for the concept of a "unique myocardial band". The method has the potential to detecting deviations from this basic normal architecture, being capable of reconstructing the ventricular mass so as to assess the spatial coordinates of any single fibre strand. The technique, therefore, has major potential clinical applications in the setting of the failing or malformed heart, potentially being able to identify either systematic or regional disarray of the myocardial fibres.

Supernormal vision, high-resolution retinal imaging, multiphoton imaging and nanosurgery of the cornea--a review.

Wavelength-corrected, adaptive optics and their relevance for diagnostic procedures of the human retina are considered. First, it is shown that the compensation of errors of the dioptric apparatus of the eye allows sharp and high-contrast images of retinal elements, such as the photoreceptors, to be generated. This technology is expected to enable on the one hand an improved laser therapy by the application of laser spots of the size of single receptors as well as on the other a further understanding of the mechanisms of vision, in particular of colour vision by using colour stimuli not larger than the cones. Second, femtosecond laser pulses, emitted from lasers working in the near infrared, based on multiphoton effects allow both imaging and laser effects to be generated which are in the submicron range and which do not cause collateral damage (nanoimaging and nanosurgery). These procedures, related to experimental ophthalmology may be considered a milestone for the research of cell physiology, in particular in the subcellular range.