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Ferran Poveda, Enric Marti, Debora Gil, Francesc Carreras, & Manel Ballester. (2012). Helical Structure of Ventricular Anatomy by Diffusion Tensor Cardiac MR Tractography. JACC - Journal of American College of Cardiology, 5(7), 754–755.
Abstract: It is widely accepted that myocardial fiber architecture plays a critical role in myocardial contractility and relaxation (1). However, there is a lack of consensus about the distribution of the myocardial fibers and their spatial arrangement in the left and right ventricles. An understanding of the cardiac architecture should benefit the ventricular functional assessment, left ventricular reconstructive surgery planning, or resynchronization therapy in heart failure. Researchers have proposed several conceptual models to describe the architecture of the heart, ranging from gross dissection to histological presentation. The cardiac mesh model (2) proposes that the myocytes are arranged longitudinally and radially change their angulation along the myocardial depth. By contrast, the helical ventricular myocardial model states that the ventricular myocardium is a continuous anatomical helical layout of myocardial fibers (1
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David Roche, Debora Gil, & Jesus Giraldo. (2013). Multiple active receptor conformation, agonist efficacy and maximum effect of the system: the conformation-based operational model of agonism,. DDT - Drug Discovery Today, 18(7-8), 365–371.
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.
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Sergio Vera, Debora Gil, Agnes Borras, Marius George Linguraru, & Miguel Angel Gonzalez Ballester. (2013). Geometric Steerable Medial Maps. MVA - Machine Vision and Applications, 24(6), 1255–1266.
Abstract: In order to provide more intuitive and easily interpretable representations of complex shapes/organs, medial manifolds should reach a compromise between simplicity in geometry and capability for restoring the anatomy/shape of the organ/volume. Existing morphological methods show excellent results when applied to 2D objects, but their quality drops across dimensions.
This paper contributes to the computation of medial manifolds in two aspects. First, we provide a standard scheme for the computation of medial manifolds that avoids degenerated medial axis segments. Second, we introduce a continuous operator for accurate and efficient computation of medial structures of arbitrary dimension. We evaluate quantitatively the performance of our method with respect to existing approaches, by applying them to syn- thetic shapes of known medial geometry. We also show its higher performance for medical imaging applications in terms of simplicity of medial structures and capability for reconstructing the anatomical volume.
Keywords: Medial Representations ,Medial Manifolds Comparation , Surface , Reconstruction
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Ferran Poveda, Debora Gil, Enric Marti, Albert Andaluz, Manel Ballester, & Francesc Carreras Costa. (2013). Helical structure of the cardiac ventricular anatomy assessed by Diffusion Tensor Magnetic Resonance Imaging multi-resolution tractography. REC - Revista Española de Cardiología, 66(10), 782–790.
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.
Keywords: Heart;Diffusion magnetic resonance imaging;Diffusion tractography;Helical heart;Myocardial ventricular band.
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David Roche, Debora Gil, & Jesus Giraldo. (2013). Mechanistic analysis of the function of agonists and allosteric modulators: Reconciling two-state and operational models. BJP - British Journal of Pharmacology, 169(6), 1189–202.
Abstract: Two-state and operational models of both agonism and allosterism are compared to identify and characterize common pharmacological parameters. To account for the receptor-dependent basal response, constitutive receptor activity is considered in the operational models. By arranging two-state models as the fraction of active receptors and operational models as the fractional response relative to the maximum effect of the system, a one-by-one correspondence between parameters is found. The comparative analysis allows a better understanding of complex allosteric interactions. In particular, the inclusion of constitutive receptor activity in the operational model of allosterism allows the characterization of modulators able to lower the basal response of the system; that is, allosteric modulators with negative intrinsic efficacy. Theoretical simulations and overall goodness of fit of the models to simulated data suggest that it is feasible to apply the models to experimental data and constitute one step forward in receptor theory formalism.
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