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.

Abstract: Distortion of Left Ventricle (LV) external anatomy is related to some dysfunctions, such as hypertrophy. The architecture of myocardial fibers determines LV electromechanical activation patterns as well as mechanics. Thus, their joined modelling would allow the design of specific interventions (such as peacemaker implantation and LV remodelling) and therapies (such as resynchronization). On one hand, accurate modelling of external anatomy requires either a dense sampling or a continuous infinite dimensional approach, which requires non-Euclidean statistics. On the other hand, computation of fiber models requires statistics on Riemannian spaces. Most approaches compute separate statistical models for external anatomy and fibers architecture. In this work we propose a general mathematical framework based on differential geometry concepts for computing a statistical model including, both, external and fiber anatomy. Our framework provides a continuous approach to external anatomy supporting standard statistics. We also provide a straightforward formula for the computation of the Riemannian fiber statistics. We have applied our methodology to the computation of complete anatomical atlas of canine hearts from diffusion tensor studies. The orientation of fibers over the average external geometry agrees with the segmental description of orientations reported in the literature.

Abstract: Optical Flow (OF) techniques facing the complexity of real sequences have been developed in the last years. Even using the most appropriate technique for our specific problem, at some points the output flow might fail to achieve the minimum error required for the system. Confidence measures computed from either input data or OF output should discard those points where OF is not accurate enough for its further use. It follows that evaluating the capabilities of a confidence measure for bounding OF error is as important as the definition
itself. In this paper we analyze different confidence measures and point out their advantages and limitations for their use in real world settings. We also explore the agreement with current tools for their evaluation of confidence measures performance.

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: Cardiac diseases are diagnosed and treated through a study of the morphology and dynamics of cardiac arteries. In- travascular Ultrasound (IVUS) imaging is of high interest to physicians since it provides both information. At the current state-of-the-art in image segmentation, a robust detection of the arterial lumen in IVUS demands manual intervention or ECG-gating. Manual intervention is a tedious and time consuming task that requires experienced observers, meanwhile ECG-gating is an acquisition technique not available in all clinical centers. We introduce a parametric algorithm that detects the arterial luminal border in in vivo sequences. The method consist in smoothing the sequences’ level surfaces under a regularized mean curvature flow that admits non-trivial steady states. The flow is based on a measure of the surface local smoothness that takes into account regularity of the surface curvature.