Cardiac q-space trajectory imaging by motion-compensated tensor-valued diffusion encoding in human heart in vivo.

PURPOSE: Tensor-valued diffusion encoding can probe more specific features of tissue microstructure than what is available by conventional diffusion weighting. In this work, we investigate the technical feasibility of tensor-valued diffusion encoding at high b-values with q-space trajectory imaging (QTI) analysis, in the human heart in vivo. METHODS: Ten healthy volunteers were scanned on a 3T scanner. We designed time-optimal gradient waveforms for tensor-valued diffusion encoding (linear and planar) with second-order motion compensation. Data were analyzed with QTI. Normal values and repeatability were investigated for the mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (µFA), isotropic, anisotropic and total mean kurtosis (MKi, MKa, and MKt), and orientation coherence (Cc ). A phantom, consisting of two fiber blocks at adjustable angles, was used to evaluate sensitivity of parameters to orientation dispersion and diffusion time. RESULTS: QTI data in the left ventricular myocardium were MD = 1.62 ± 0.07 µm2 /ms, FA = 0.31 ± 0.03, µFA = 0.43 ± 0.07, MKa = 0.20 ± 0.07, MKi = 0.13 ± 0.03, MKt = 0.33 ± 0.09, and Cc  = 0.56 ± 0.22 (mean ± SD across subjects). Phantom experiments showed that FA depends on orientation dispersion, whereas µFA was insensitive to this effect. CONCLUSION: We demonstrated the first tensor-valued diffusion encoding and QTI analysis in the heart in vivo, along with first measurements of myocardial µFA, MKi, MKa, and Cc . The methodology is technically feasible and provides promising novel biomarkers for myocardial tissue characterization.

Endothelial IGF-1 receptor mediates crosstalk with the gut wall to regulate microbiota in obesity.

Changes in composition of the intestinal microbiota are linked to the development of obesity and can lead to endothelial cell (EC) dysfunction. It is unknown whether EC can directly influence the microbiota. Insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) are critical for coupling nutritional status and cellular growth; IGF-1R is expressed in multiple cell types including EC. The role of ECIGF-1R in the response to nutritional obesity is unexplored. To examine this, we use gene-modified mice with EC-specific overexpression of human IGF-1R (hIGFREO) and their wild-type littermates. After high-fat feeding, hIGFREO weigh less, have reduced adiposity and have improved glucose tolerance. hIGFREO show an altered gene expression and altered microbial diversity in the gut, including a relative increase in the beneficial genus Akkermansia. The depletion of gut microbiota with broad-spectrum antibiotics induces a loss of the favourable metabolic differences seen in hIGFREO mice. We show that IGF-1R facilitates crosstalk between the EC and the gut wall; this crosstalk protects against diet-induced obesity, as a result of an altered gut microbiota.

Macro-Scale Tread Patterns for Traction in the Intestine.

GOAL: Tread patterns are widely used to increase traction on different substrates, with the tread scale, geometry and material being tailored to the application. This work explores the efficacy of using macro-scale tread patterns for a medical application involving a colon substrate - renowned for its low friction characteristics. METHODS: Current literature was first summarized before an experimental approach was used, based on a custom test rig with ex vivo porcine colon, to assess different macro-scale tread patterns. Performance was based on increasing traction while avoiding significant trauma. Repeated testing (n = 16) was used to obtain robust results. RESULTS: A macro-scale tread pattern can increase the traction coefficient significantly, with a static traction coefficient of 0.74 ± 0.22 and a dynamic traction coefficient of 0.35 ± 0.04 compared to a smooth (on the macro-scale) Control (0.132 ± 0.055 and 0.054 ± 0.015, respectively). Decreasing the scale and spacing between the tread features reduced apparent trauma but also reduced the traction coefficient. CONCLUSION: Significant traction can be achieved on colon tissue using a macro-scale tread but a compromise between traction (large feature sizes) and trauma (small feature sizes) may have to be made. SIGNIFICANCE: This work provides greater insight into the complex frictional mechanisms of the intestine and gives suggestions for developing functional tread surfaces for a wide range of clinical applications.

Gait Modulation in C. elegans: An Integrated Neuromechanical Model.

Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans adapts its locomotion in different environments, exhibiting so-called swimming in liquids and crawling on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism. We present a model of C. elegans forward locomotion that includes a neuromuscular control system that relies on a sensory feedback mechanism to generate undulations and is integrated with a physical model of the body and environment. We find that the model reproduces the entire swim-crawl transition, as well as locomotion in complex and heterogeneous environments. This is achieved with no modulatory mechanism, except via the proprioceptive response to the physical environment. Manipulations of the model are used to dissect the proposed pattern generation mechanism and its modulation. The model suggests a possible role for GABAergic D-class neurons in forward locomotion and makes a number of experimental predictions, in particular with respect to non-linearities in the model and to symmetry breaking between the neuromuscular systems on the ventral and dorsal sides of the body.

Forward locomotion of the nematode C. elegans is achieved through modulation of a single gait.

The ability of an animal to locomote through its environment depends crucially on the interplay between its active endogenous control and the physics of its interactions with the environment. The nematode worm Caenorhabditis elegans serves as an ideal model system for studying the respective roles of neural control and biomechanics, as well as the interaction between them. With only 302 neurons in a hard-wired neural circuit, the worm's apparent anatomical simplicity belies its behavioural complexity. Indeed, C. elegans exhibits a rich repertoire of complex behaviors, the majority of which are mediated by its adaptive undulatory locomotion. The conventional wisdom is that two kinematically distinct C. elegans locomotion behaviors-swimming in liquids and crawling on dense gel-like media-correspond to distinct locomotory gaits. Here we analyze the worm's motion through a series of different media and reveal a smooth transition from swimming to crawling, marked by a linear relationship between key locomotion metrics. These results point to a single locomotory gait, governed by the same underlying control mechanism. We further show that environmental forces play only a small role in determining the shape of the worm, placing conditions on the minimal pattern of internal forces driving locomotion.

Caenorhabditis elegans body wall muscles are simple actuators.

Over the past four decades, one of the simplest nervous systems across the animal kingdom, that of the nematode worm Caenorhabditis elegans, has drawn increasing attention. This system is the subject of an intensive concerted effort to understand the behaviour of an entire living animal, from the bottom up and the top down. C. elegans locomotion, in particular, has been the subject of a number of models, but there is as yet no general agreement about the key (rhythm generating) elements. In this paper we investigate the role of one component of the locomotion subsystem, namely the body wall muscles, with a focus on the role of inter-muscular gap junctions. We construct a detailed electrophysiological model which suggests that these muscles function, to a first approximation, as mere actuators and have no obvious rhythm generating role. Furthermore, we show that within our model inter-muscular coupling is too weak to have a significant electrical effect. These results rule out muscles as key generators of locomotion, pointing instead to neural activity patterns. More specifically, the results imply that the reduced locomotion velocity observed in unc-9 mutants is likely to be due to reduced neuronal rather than inter-muscular coupling.