Abstract: The operational model of agonism has been widely used for the analysis of agonist action since its formulation in 1983. The model includes the Em parameter, which is defined as the maximum response of the system. The methods for Em estimation provide Em values not significantly higher than the maximum responses achieved by full agonists. However, it has been found that that some classes of compounds as, for instance, superagonists and positive allosteric modulators can increase the full agonist maximum response, implying upper limits for Em and thereby posing doubts on the validity of Em estimates. Because of the correlation between Em and operational efficacy, τ, wrong Em estimates will yield wrong τ estimates.
In this presentation, the operational model of agonism and various methods for the simulation of allosteric modulation will be analyzed. Alternatives for curve fitting will be presented and discussed.

Abstract: Myocardial torsion (MT) plays a crucial role in the assessment of the functionality of the
left ventricle. For this purpose, the IAM group at the CVC has developed the Harmonic Phase Flow (HPF) plugin for the Osirix DICOM platform . We have validated its funcionalty on sequences acquired using different protocols and including healthy and pathological cases. Results show similar torsion trends for SPAMM acquisitions, with pathological cases introducing expected deviations from the ground truth. Finally, we provide the plugin free of charge at http://iam.cvc.uab.es

Abstract: Computational simulations of the heart are a powerful tool for a comprehensive understanding of cardiac function and its intrinsic relationship with its muscular architecture. Cardiac biomechanical models require a vector field representing the orientation of cardiac fibers. A wrong orientation of the fibers can lead to a
non-realistic simulation of the heart functionality. In this paper we explore the impact of the fiber information on the simulated biomechanics of cardiac muscular anatomy. We have used the John Hopkins database to perform a biomechanical simulation using both a synthetic benchmark fiber distribution and the data obtained experimentally from DTI. Results illustrate how differences in fiber orientation affect heart deformation along cardiac cycle.

Abstract: Early diagnosis and accurate treatment of Left Ventricle (LV) dysfunction significantly increases the patient survival. Impairment of LV contractility due to cardiovascular diseases is reflected in its motion patterns. Recent advances in medical imaging, such as Magnetic Resonance (MR), have encouraged research on 3D simulation and modelling of the LV dynamics. Most of the existing 3D models [1] consider just the gross anatomy of the LV and restore a truncated ellipse which deforms along the cardiac cycle. The contraction mechanics of any muscle strongly depends on the spatial orientation of its muscular fibers since the motion that the muscle undergoes mainly takes place along the fibers. It follows that such simplified models do not allow evaluation of the heart electro-mechanical function and coupling, which has recently risen as the key point for understanding the LV functionality [2]. In order to thoroughly understand the LV mechanics it is necessary to consider the complete anatomy of the LV given by the orientation of the myocardial fibres in 3D space as described by Torrent Guasp [3].
We propose developing a 3D patient-sensitive model of the LV integrating, for the first time, the ven- tricular band anatomy (fibers orientation), the LV gross anatomy and its functionality. Such model will represent the LV function as a natural consequence of its own ventricular band anatomy. This might be decisive in restoring a proper LV contraction in patients undergoing pace marker treatment.
The LV function is defined as soon as the propagation of the contractile electromechanical pulse has been modelled. In our experiments we have used the wave equation for the propagation of the electric pulse. The electromechanical wave moves on the myocardial surface and should have a conductivity tensor oriented along the muscular fibers. Thus, whatever mathematical model for electric pulse propa- gation [4] we consider, the complete anatomy of the LV should be extracted.
The LV gross anatomy is obtained by processing multi slice MR images recorded for each patient. Information about the myocardial fibers distribution can only be extracted by Diffusion Tensor Imag- ing (DTI), which can not provide in vivo information for each patient. As a first approach, we have
Figure 1: Scheme for the Left Ventricle Patient-Sensitive Model.
computed an average model of fibers from several DTI studies of canine hearts. This rough anatomy is the input for our electro-mechanical propagation model simulating LV dynamics. The average fiber orientation is updated until the simulated LV motion agrees with the experimental evidence provided by the LV motion observed in tagged MR (TMR) sequences. Experimental LV motion is recovered by applying image processing, differential geometry and interpolation techniques to 2D TMR slices [5]. The pipeline in figure 1 outlines the interaction between simulations and experimental data leading to our patient-tailored model.