Computational Representation of White Matter Fiber Orientations

We present a new methodology based on directional data clustering to represent white matter fiber orientations in magnetic resonance analyses for high angular resolution diffusion imaging. A probabilistic methodology is proposed for estimating intravoxel principal fiber directions, based on clustering directional data arising from orientation distribution function (ODF) profiles. ODF reconstructions are used to estimate intravoxel fiber directions using mixtures of von Mises-Fisher distributions. The method focuses on clustering data on the unit sphere, where complexity arises from representing ODF profiles as directional data. The proposed method is validated on synthetic simulations, as well as on a real data experiment. Based on experiments, we show that by clustering profile data using mixtures of von Mises-Fisher distributions it is possible to estimate multiple fiber configurations in a more robust manner than currently used approaches, without recourse to regularization or sharpening procedures. The method holds promise to support robust tractographic methodologies and to build realistic models of white matter tracts in the human brain

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

A self-learning algorithm for biased molecular dynamics

A new self-learning algorithm for accelerated dynamics, reconnaissance metadynamics, is proposed that is able to work with a very large number of collective coordinates. Acceleration of the dynamics is achieved by constructing a bias potential in terms of a patchwork of one-dimensional, locally valid collective coordinates. These collective coordinates are obtained from trajectory analyses so that they adapt to any new features encountered during the simulation. We show how this methodology can be used to enhance sampling in real chemical systems citing examples both from the physics of clusters and from the biological sciences.Comment: 6 pages, 5 figures + 9 pages of supplementary informatio

Kinetic distance and kinetic maps from molecular dynamics simulation

Characterizing macromolecular kinetics from molecular dynamics (MD) simulations requires a distance metric that can distinguish slowly-interconverting states. Here we build upon diffusion map theory and define a kinetic distance for irreducible Markov processes that quantifies how slowly molecular conformations interconvert. The kinetic distance can be computed given a model that approximates the eigenvalues and eigenvectors (reaction coordinates) of the MD Markov operator. Here we employ the time-lagged independent component analysis (TICA). The TICA components can be scaled to provide a kinetic map in which the Euclidean distance corresponds to the kinetic distance. As a result, the question of how many TICA dimensions should be kept in a dimensionality reduction approach becomes obsolete, and one parameter less needs to be specified in the kinetic model construction. We demonstrate the approach using TICA and Markov state model (MSM) analyses for illustrative models, protein conformation dynamics in bovine pancreatic trypsin inhibitor and protein-inhibitor association in trypsin and benzamidine