Srinivasan Sivanandan

Congenital heart disease is the leading cause of birth defect related deaths. The modified myocardial performance index of the right ventricle (R-MPI) is a sensitive and early clinical indicator of fetal cardiac health. Objective repeatable measurement of R-MPI is an important deciding factor for the clinical adaptation of the R-MPI. In this work, we describe a novel method for automatic computation of R-MPI from the Pulsed Wave Doppler (PWD) images. Our method involves a Fourier series based… Show more

Congenital heart disease is the leading cause of birth defect related deaths. The modified myocardial performance index of the right ventricle (R-MPI) is a sensitive and early clinical indicator of fetal cardiac health. Objective repeatable measurement of R-MPI is an important deciding factor for the clinical adaptation of the R-MPI. In this work, we describe a novel method for automatic computation of R-MPI from the Pulsed Wave Doppler (PWD) images. Our method involves a Fourier series based cardiac cycle detection followed by an adaptive windowed energy based valve click localization and weighted gradient based refinement. Using this method, we have been able to measure R-MPI reliably with a mean difference of 0.0075 ± 0.034 from 170 expert annotations on 68 fetal PWD images with an Intra-Class Correlation (ICC) of 0.9380. Furthermore, we have introduced novel methods for normalization and synchronization of PWD images acquired at two different time intervals for the assessment of iso-volume time intervals and an accurate measurement of R-MPI. Show less

Follicle quantification refers to the computation of the number and size of follicles in 3D ultrasound volumes of the ovary. This is one of the key factors in determining hormonal dosage during female infertility treatments. In this paper, we propose an automated algorithm to detect and segment follicles in 3D ultrasound volumes of the ovary for quantification. In a first of its kind attempt, we employ noise-robust phase symmetry feature maps as likelihood function to perform mean-shift based… Show more

Follicle quantification refers to the computation of the number and size of follicles in 3D ultrasound volumes of the ovary. This is one of the key factors in determining hormonal dosage during female infertility treatments. In this paper, we propose an automated algorithm to detect and segment follicles in 3D ultrasound volumes of the ovary for quantification. In a first of its kind attempt, we employ noise-robust phase symmetry feature maps as likelihood function to perform mean-shift based follicle center detection. Max-flow algorithm is used for segmentation and gray weighted distance transform is employed for post-processing the results. We have obtained state-of-the-art results with a true positive detection rate of >90% on 26 3D volumes with 323 follicles. Show less

The stability of the repeat protein IκBα, a transcriptional inhibitor in mammalian cells, is critical in the functioning of the NF-κB signaling module implicated in an array of cellular processes, including cell growth, disease, immunity and apoptosis. Structurally, IκBα is complex, with both ordered and disordered regions, thus posing a challenge to the available computational protocols to model its conformational behavior. Here, we introduce a simple procedure to model disorder in systems… Show more

The stability of the repeat protein IκBα, a transcriptional inhibitor in mammalian cells, is critical in the functioning of the NF-κB signaling module implicated in an array of cellular processes, including cell growth, disease, immunity and apoptosis. Structurally, IκBα is complex, with both ordered and disordered regions, thus posing a challenge to the available computational protocols to model its conformational behavior. Here, we introduce a simple procedure to model disorder in systems that undergo binding-induced folding that involves modulation of the contact map guided by equilibrium experimental observables in combination with an Ising-like Wako-Saitô-Muñoz-Eaton model. This one-step procedure alone is able to reproduce a variety of experimental observables, including ensemble thermodynamics (scanning calorimetry, pre-transitions, m-values) and kinetics (roll-over in chevron plot, intermediates and their identity), and is consistent with hydrogen-deuterium exchange measurements. We further capture the intricate distance-dynamics between the domains as measured by single-molecule FRET by combining the model predictions with simple polymer physics arguments. Our results reveal a unique mechanism at work in IκBα folding, wherein disorder in one domain initiates a domino-like effect partially destabilizing neighboring domains, thus highlighting the effect of symmetry-breaking at the level of primary sequences. The offshoot is a multi-state and a dynamic conformational landscape that is populated by increasingly partially folded ensembles upon destabilization. Our results provide, in a straightforward fashion, a rationale to the promiscuous binding and short intracellular half-life of IκBα evolutionarily engineered into it through repeats with variable stabilities and expand the functional repertoire of disordered regions in proteins. Show less