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: Corners and junctions are landmarks characterized by the lack of differentiability in the unit tangent to the image level curve. Detectors based on differential operators are not, by their own definition, the best posed as they require a higher degree of differentiability to yield a reliable response. We argue that a corner detector should be based on the degree of continuity of the tangent vector to the image level sets, work on the image domain and need no assumptions on neither the image local structure nor the particular geometry of the corner/junction. An operator measuring the degree of differentiability of the projection matrix on the image gradient fulfills the above requirements. Because using smoothing kernels leads to corner misplacement, we suggest an alternative fake response remover based on the receptive field inhibition of spurious details. The combination of both orientation discontinuity detection and noise inhibition produce our inhibition orientation energy (IOE) landmark locator.

Abstract: A good reliable approach to cardiac triggering is of utmost importance in obtaining accurate quantitative results of atherosclerotic plaque burden from the analysis of IntraVascular UltraSound. Although, in the last years, there has been an increase in research of methods for retrospective gating, there is no general consensus in a validation protocol. Many methods are based on quality assessment of longitudinal cuts appearance and those reporting quantitative numbers do not follow a standard protocol. Such heterogeneity in validation protocols makes faithful comparison across methods a difficult task. We propose a validation protocol based on the variability of the retrieved cardiac phase and explore the capability of several quality measures for quantifying such variability. An ideal detector, suitable for its application in clinical practice, should produce stable phases. That is, it should always sample the same cardiac cycle fraction. In this context, one should measure the variability (variance) of a candidate sampling with respect a ground truth (reference) sampling, since the variance would indicate how spread we are aiming a target. In order to quantify the deviation between the sampling and the ground truth, we have considered two quality scores reported in the literature: signed distance to the closest reference sample and distance to the right of each reference sample. We have also considered the residuals of the regression line of reference against candidate sampling. The performance of the measures has been explored on a set of synthetic samplings covering different cardiac cycle fractions and variabilities. From our simulations, we conclude that the metrics related to distances are sensitive to the shift considered while the residuals are robust against fraction and variabilities as far as one can establish a pair-wise correspondence between candidate and reference. We will further investigate the impact of false positive and negative detections in experimental data.

Abstract: In this work, we present a fully automated method for tissue deformation estimation in tagged magnetic resonance images (TMRI). Gabor filter banks, tuned independently for each left ventricle level, provide optimally filtered complex images which phase remains constant along the cardiac cycle. This fact can be thought as the brightness constancy condition required by classical optical flow (OF) methods. Pairs of these filtered sequences, together with a variational formulation are used in a second step to obtain dense continuous deformation maps that we call Harmonic Phase Flow. This method has been used to determine reference values of ventricular torsion (VT) in a set of 8 healthy volunteers. The results encourage the use of VT as a useful parameter for ventricular function assessment in clinical routine.