Classification and Segmentation of Nanoparticle Diffusion Trajectories in Cellular Micro Environments.

Darkfield and confocal laser scanning microscopy both allow for a simultaneous observation of live cells and single nanoparticles. Accordingly, a characterization of nanoparticle uptake and intracellular mobility appears possible within living cells. Single particle tracking allows to measure the size of a diffusing particle close to a cell. However, within the more complex system of a cell's cytoplasm normal, confined or anomalous diffusion together with directed motion may occur. In this work we present a method to automatically classify and segment single trajectories into their respective motion types. Single trajectories were found to contain more than one motion type. We have trained a random forest with 9 different features. The average error over all motion types for synthetic trajectories was 7.2%. The software was successfully applied to trajectories of positive controls for normal- and constrained diffusion. Trajectories captured by nanoparticle tracking analysis served as positive control for normal diffusion. Nanoparticles inserted into a diblock copolymer membrane was used to generate constrained diffusion. Finally we segmented trajectories of diffusing (nano-)particles in V79 cells captured with both darkfield- and confocal laser scanning microscopy. The software called "TraJClassifier" is freely available as ImageJ/Fiji plugin via https://git.io/v6uz2.

Diblock copolymer membranes investigated by single-particle tracking.

We report a study on particle diffusion in membranes formed from polystyrene-block-poly(2-(dimethylamino)ethyl methacrylate) (PS-b-PDMAEMA) diblock copolymers. The membranes were investigated by scanning electron microscopy and by single-particle tracking employing carboxy-functionalized polystyrene beads loaded with a fluorophore as spectroscopic probes. From the diffusion trajectories we extracted the domain size distribution of the membranes and the local diffusion coefficient of the beads as a function of the size of the beads. The single-particle tracking data revealed that the effective domain sizes of the membranes are reduced with respect to the domain sizes obtained from scanning electron microscopy, reflecting the confined diffusion of the probe particles due to interactions with the domain walls. This is corroborated by a clear correlation between the diffusion coefficient of an individual polystyrene bead and the size of the actual domain to which it is confined.

Nonrigid image registration with subdivision lattices: application to cardiac MR image analysis.

In this paper we present a new methodology for cardiac motion tracking in tagged MRI using nonrigid image registration based on subdivision surfaces and subdivision lattices. We use two sets of registrations to do the motion tracking. First, a set of surface registrations is used to create and initially align the subdivision model of the left ventricle with short-axis and long-axis MR images. Second, a series of volumetric registrations are used to perform the motion tracking and to reconstruct the 4D cardiac motion field from the tagged MR images. The motion of a point in the myocardium over time is calculated by registering the images taken during systole to the set of reference images taken at end-diastole. Registration is achieved by optimizing the positions of the vertices in the base lattice so that the mutual information of the images being registered is maximized. The presented method is validated using a cardiac motion simulator and we also present strain measurements obtained from a group of normal volunteers.

Thermal study of accumulation of conformational disorders in the self-assembled monolayers of C8 and C18 alkanethiols on the Au111 surface.

The thermal stability of short alkanethiol CH(3)(CH(2))(7)SH (C(8)) and long C(18) self-assembled monolayers (SAMs) is investigated using grazing angle reflection-absorption infrared spectroscopy, cyclic voltammetry, and molecular dynamics simulation. We track the disordering of SAM by untilting and gauche defect accumulation with increasing temperature in the 300-440 K range, a range of interest to tribology. Molecular dynamics simulation with both fully covered and partially covered C(6), C(8), and C(18) monolayers brings out the morphological changes in the SAM, which may be associated with the observed thermal stability characteristics. The molecular dynamics simulations reveal that short-chain C(6) and C(8) alkanethiols are more defective at lower temperature than the long-chain C(18) alkanethiol. With increasing temperature disorder in the SAM, as reflected in both untilting and gauche defect accumulation, tends to saturate at temperatures below 360 K for short-chain SAMs such that any further increase in temperature, until desorption, does not lead to any significant change in conformational order. In contrast the disorder in the long-chain C(18) SAM increases monotonically with temperature beyond 360 K. Thus, in a practical range of temperature, the ability of a SAM to retain order with increasing thermal perturbations is governed by the state of disorder prior to heat treatment. This deduction derived from molecular dynamics simulation helps to rationalize the significant difference we have observed experimentally between the thermal response of short- and long-chain thiol molecules.

Localization of abnormal conduction pathways for tachyarrhythmia treatment using tagged MRI.

Tachyarrhythmias are pathological fast heart rhythms often caused by abnormally conducting myocardial areas (foci). Treatment by radio-frequency (RF) ablation uses electrode-catheters to monitor and destroy foci. The procedure is normally guided with x-rays (2D), and thus prone to errors in location and excessive radiation exposure. Our main goal is to provide pre- and intra-operative 3D MR guidance in XMR systems by locating the abnormal conduction pathways. We address the inverse electro-mechanical relation by using motion in order to infer electrical propagation. For this purpose we define a probabilistic measure of the onset of regional myocardial activation, derived from 3D motion fields obtained by tracking tagged MR sequences with non-rigid registration. Activation isochrones are then derived to determine activation onset. We also compare regional motion between two different image acquisitions, thus assisting in diagnosing arrhythmia, in follow up of treatment, and in determining whether the ablation was successful. Difference maps of isochrones and other motion descriptors are computed to determine abnormal patterns. Validation was carried out using an electromechanical model of the heart, synthetic data, a cardiac MRI atlas of motion and geometry, MRI data from 6 healthy volunteers (one of them subjected to stress), and an MRI study on a patient with tachyarrhythmia, before and after RF ablation. A pre-operative MRI study on a second patient with tachyarrhythmia was used to test the methodology in a clinical scenario, predicting the abnormally conducting region.

Spatial transformation of motion and deformation fields using nonrigid registration.

In this paper, we present a technique that can be used to transform the motion or deformation fields defined in the coordinate system of one subject into the coordinate system of another subject. Such a transformation accounts for the differences in the coordinate systems of the two subjects due to misalignment and size/shape variation, enabling the motion or deformation of each of the subjects to be directly quantitatively and qualitatively compared. The field transformation is performed by using a nonrigid registration algorithm to determine the intersubject coordinate system mapping from the first subject to the second subject. This fixes the relationship between the coordinate systems of the two subjects, and allows us to recover the deformation/motion vectors of the second subject for each corresponding point in the first subject. Since these vectors are still aligned with the coordinate system of the second subject, the inverse of the intersubject coordinate mapping is required to transform these vectors into the coordinate system of the first subject, and we approximate this inverse using a numerical line integral method. The accuracy of our numerical inversion technique is demonstrated using a synthetic example, after which we present applications of our method to sequences of cardiac and brain images.