Abstract: The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators that significantly increase the maximum effect of endogenous agonists. An extension of the operational model is proposed that assumes that the Em parameter does not necessarily have a single value for a receptor system but has multiple values associated to multiple active receptor conformations. The model provides a mechanistic link between active receptor conformation and agonist efficacy, which can be useful for the analysis of agonist response under different receptor scenarios.

Abstract: Deep understanding of myocardial structure linking 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 in this knowledge through advanced computer graphic representations of the myocardial fiber architecture by diffusion tensor magnetic resonance imaging (DT-MRI).
We performed automatic tractography reconstruction of unsegmented DT-MRI canine heart datasets coming from the public database of the Johns Hopkins University. Full scale tractographies have been build with 200 seeds and are composed by streamlines computed on the vectorial field of primary eigenvectors given at the diffusion tensor volumes. Also, we introduced a novel multi-scale visualization technique in order to obtain a simplified tractography. This methodology allowed to keep the main geometric features of the fiber tracts, making easier to decipher the main properties of the architectural organization of the heart.
On the analysis of the output from our tractographic representations we found exact correlation with low-level details of myocardial architecture, but also with the more abstract conceptualization of a continuous helical ventricular myocardial fiber array.
Objective analysis of myocardial architecture by an automated method, including the entire myocardium and using several 3D 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 Torrent-Guasp.

Abstract: 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 ventric- ular 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 obser- vational 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.

Abstract: Deep understanding of myocardial structure linking morphology and func- tion of the heart would unravel crucial knowledge for medical and surgical clinical procedures and studies. Diffusion tensor MRI provides a discrete measurement of the 3D arrangement of myocardial fibres by the observation of local anisotropic
diffusion of water molecules in biological tissues. In this work, we present a multi- scale visualisation technique based on DT-MRI streamlining capable of uncovering additional properties of the architectural organisation of the heart. Methods and Materials: We selected the John Hopkins University (JHU) Canine Heart Dataset, where the long axis cardiac plane is aligned with the scanner’s Z- axis. Their equipment included a 4-element passed array coil emitting a 1.5 T. For DTI acquisition, a 3D-FSE sequence is apply. We used 200 seeds for full-scale tractography, while we applied a MIP mapping technique for simplified tractographic reconstruction. In this case, we reduced each DTI 3D volume dimensions by order- two magnitude before streamlining.
Our simplified tractographic reconstruction method keeps the main geometric features of fibres, allowing for an easier identification of their global morphological disposition, including the ventricular basal ring. Moreover, we noticed a clearly visible helical disposition of the myocardial fibres, in line with the helical myocardial band ventricular structure described by Torrent-Guasp. Finally, our simplified visualisation with single tracts identifies the main segments of the helical ventricular architecture.
DT-MRI makes possible the identification of a continuous helical architecture of the myocardial fibres, which validates Torrent-Guasp’s helical myocardial band ventricular anatomical model.

Abstract: This paper presents a patient-sensitive simulation strategy capable of using the most efficient way the high-performance computational resources. The proposed strategy directly involves three different players: Computational Mechanics Scientists (CMS), Image Processing Scientists and Cardiologists, each one mastering its own expertise area within the project. This paper describes the general integrative scheme but focusing on the CMS side presents a massively parallel implementation of computational electrophysiology applied to cardiac tissue simulation. The paper covers different angles of the computational problem: equations, numerical issues, the algorithm and parallel implementation. The proposed methodology is illustrated with numerical simulations testing all the different possibilities, ranging from small domains up to very large ones. A key issue is the almost ideal scalability not only for large and complex problems but also for medium-size meshes. The explicit formulation is particularly well suited for solving this highly transient problems, with very short time-scale.