Biomagnetic signatures of uncoupled gastric musculature

Gastric slow waves propagate in the electrical syncytium of the healthy stomach, being generated at a rate of approximately three times per minute in a pacemaker region along the greater curvature of the antrum and propagating distally towards the pylorus. Disease states are known to alter the normal gastric slow wave. Recent studies have suggested the use of biomagnetic techniques for assessing parameters of the gastric slow wave that have potential diagnostic significance. We present a study in which the gastric syncytium was uncoupled by mechanical division as we recorded serosal electric potentials along with multichannel biomagnetic signals and cutaneous potentials. By computing the surface current density (SCD) from multichannel biomagnetic recordings, we were able to quantify gastric slow wave propagation as well as the frequency and amplitude of the slow wave and to show that these correlate well with similar parameters from serosal electrodes. We found the dominant slow wave frequency to be an unreliable indicator of gastric uncoupling as uncoupling results in the appearance of multiple slow wave sources at various frequencies in external recordings. The percentage of power distributed in specific frequency ranges exhibited significant postdivision changes. Propagation velocity determined from SCD maps was a weak indicator of uncoupling in this work; we believe that the relatively low spatial resolution of our 19-channel biomagnetometer confounds the characterization of spatial variations in slow wave propagation velocities. Nonetheless, the biomagnetic technique represents a non-invasive method for accurate determination of clinically significant parameters of the gastric slow wave

Atrial conduction velocity mapping: clinical tools, algorithms and approaches for understanding the arrhythmogenic substrate

Characterizing patient-specific atrial conduction properties is important for understanding arrhythmia drivers, for predicting potential arrhythmia pathways, and for personalising treatment approaches. One metric that characterizes the health of the myocardial substrate is atrial conduction velocity, which describes the speed and direction of propagation of the electrical wavefront through the myocardium. Atrial conduction velocity mapping algorithms are under continuous development in research laboratories and in industry. In this review article, we give a broad overview of different categories of currently published methods for calculating CV, and give insight into their different advantages and disadvantages overall. We classify techniques into local, global, and inverse methods, and discuss these techniques with respect to their faithfulness to the biophysics, incorporation of uncertainty quantification, and their ability to take account of the atrial manifold

A multi-compartmental mathematical model of the postprandial human stomach : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Anatomy and Physiology at Massey University, Palmerston North, New Zealand

Computational fluid dynamics of the human stomach helps to understand the gastric processes such as trituration, mixing, and transit of digesta. Their outcomes give greater insight into the design of food and orally dosed drug delivery system. Current models of gastric contractile activity are primarily limited to the gastric antrum and assume global values for the various physiological characteristics. This thesis developed a unified compartmental gastric model with correctly informed anatomical and physiological data. The gastric geometry incorporated the actions of multiple compartments, such as the gastric fundus, body, antrum, pyloric canal, proximal duodenal cap, and the small intestinal brake. Lattice-Boltzmann Method (LBM) is used to simulate the fluid dynamics within the stomach. This thesis quantified the effects of transgastric pressure gradient (TGPG) between the fundus and the duodenum, the effect of antral propagating contraction (APC) amplitude, and the viscosity of the gastric contents on gastric flow, mixing, and gastric emptying. The results of this work suggest that TGPG influences gastric emptying where as APCs do not play major role in gastric emptying. Flow rate without TGPG obtained in this work agrees with previous work (Pal et al., 2004); however, it is higher in the presence of a TGPG. Results show that APCs promote recirculation, and the amplitude of APC is vital in this regard. The 'pendulating' flow of gastric content observed in this work is reported previously in duplex sonography experiments (Hausken et al., 1992). This work quantified the gastric shear rates (0.6 - 2.0 /s). This work also suggests that the viscosity of the content influences gastric fluid dynamics. This work is a simplified first step towards a 3D gastric model. Hence, these simulation studies were performed under two simplifications: dimensionality and rheology, i.e., we have assumed a Newtonian fluid flow in 2D gastric geometry. A 3D gastric model with more rheologically realistic fluid to explore the pseudoplastic fluid dynamics within the stomach in the future is recommended

Mechanistic Analysis and Quantification of Gastrointestinal Motility: Physiological Variability and Plasma Level Implications.

The oral route of administration is still by far the most ubiquitous method of drug delivery. Development in this area still faces many challenges due to the complex inhomogeneity of the gastrointestinal environment. In particular, gastric emptying and gastrointestinal motility is not predictable and so dosing occurs randomly with respect to these physiological variables. The goal of this research is to present a mass balance analysis that captures this variation, highlighting the effects of motility and exploring how it ultimately impacts plasma levels and the relationship to bioequivalence. A mechanistic analysis is first developed describing the underlying fasted state cyclical motility and how the contents of the gastrointestinal tract are propelled. This physiologically based approach allows the estimation of potential absorption ranges based on uncontrolled variation. Validation of the simulations is based on reported gastric emptying profiles and volumetric emptying as well as previous experimental works on gastrointestinal transit times, and the bioequivalence implications of such variation are also considered. Next, a dissolution model is presented to account for the dynamics of physiological conditions along the gastrointestinal tract, including small volumes and variable pH profiles. Predicting the extent of dissolution along with transit profiles of dissolved and particulate content is crucial to approximating absorption. Ibuprofen and phenol red are used as example cases. Finally, a method for refining the gastrointestinal transit model is critical for ensuring accuracy, and a methodology is presented for extracting relevant information from intubation studies. Gastrointestinal manometry can be thought of as a stochastic process in which the indeterminacy of state transition times belies absolute periodicity of the system. To account for this inherent randomness, the use of statistical computing can identify and characterize the different phases of the gastrointestinal cycle. Specifically, a Gaussian process is used as a robust regression method to model the time-dependent evolution of the signal. As further validation, using a pressure peak detection method based on continuous wavelet transforms and subsequently a kernel density estimator as a smoothing function, regression-based motility phase classification corresponds expected pressure peak density estimates.PhDPharmaceutical SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113403/1/arjang_1.pd

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on

Advances in Hyperspectral and Multispectral Optical Spectroscopy and Imaging of Tissue

The purpose of this SI is to provide an overview of recent advances made in the methods used for tissue imaging and characterization, which benefit from using a large range of optical wavelengths. Guerouah et al. has contributed a profound study of the responses of the adult human brain to breath-holding challenges based on hyperspectral near-infrared spectroscopy (hNIRS). Lange et al. contributed a timely and comprehensive review of the features and biomedical and clinical applications of supercontinuum laser sources. Blaney et al. reported the development of a calibration-free hNIRS system that can measure the absolute and broadband absorption and scattering spectra of turbid media. Slooter et al. studied the utility of measuring multiple tissue parameters simultaneously using four optical techniques operating at different wavelengths of light—optical coherence tomography (1300 nm), sidestream darkfield microscopy (530 nm), laser speckle contrast imaging (785 nm), and fluorescence angiography (~800 nm)—in the gastric conduit during esophagectomy. Caredda et al. showed the feasibility of accurately quantifying the oxy- and deoxy-hemoglobin and cytochrome-c-oxidase responses to neuronal activation and obtaining spatial maps of these responses using a setup consisting of a white light source and a hyperspectral or standard RGB camera. It is interest for the developers and potential users of clinical brain and tissue optical monitors, and for researchers studying brain physiology and functional brain activity

Comparison of electrohysterogram signal measured by surface electrodes with different designs: A computational study with dipole band and abdomen models

Non-invasive measurement of uterine activity using electrohysterogram (EHG) surface electrodes has been attempted to monitor uterine contraction. This study aimed to computationally compare the performance of acquiring EHG signals using monopolar electrode and three types of Laplacian concentric ring electrodes (bipolar, quasi-bipolar and tri-polar). With the implementation of dipole band model and abdomen model, the performances of four electrodes in terms of the local sensitivity were quantifed by potential attenuation. Furthermore, the efects of fat and muscle thickness on potential attenuation were evaluated using the bipolar and tri-polar electrodes with diferent radius. The results showed that all the four types of electrodes detected the simulated EHG signals with consistency. That the bipolar and tri-polar electrodes had greater attenuations than the others, and the shorter distance between the origin and location of dipole band at 20dB attenuation, indicating that they had relatively better local sensitivity. In addition, ANOVA analysis showed that, for all the electrodes with diferent outer ring radius, the efects of fat and muscle on potential attenuation were signifcant (all p<0.01). It is therefore concluded that the bipolar and tri-polar electrodes had higher local sensitivity than the others, indicating that they can be applied to detect EHG efectively

Altered Gastrointestinal Motility in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that causes motor, visual, and sensory symptoms. Patients also experience constipation, which is not yet understood, but could involve dysfunction of the enteric nervous system (ENS). Autoimmune targeting of the ENS occurs in other autoimmune diseases that exhibit gastrointestinal (GI) symptoms, and similar mechanisms could lead to GI dysfunction in MS. Here, we characterize GI dysmotility in the experimental autoimmune encephalomyelitis (EAE) model of MS and test whether autoantibodies targeting the ENS are present in the serum of MS patients. Male SJL or B6 mice were induced with EAE by immunization against PLP139-151, MOG35-55, or mouse spinal cord homogenate, and monitored daily for somatic motor symptoms. EAE mice developed GI symptoms consistent with those observed in MS. In vivo motility analysis demonstrated slower whole GI transit, and decreased colonic propulsive motility. EAE mice had faster rates of gastric emptying, with no changes in small intestinal motility. Consistent with these results, ex vivo evaluation of isolated colons demonstrated that EAE mice have slower colonic migrating myoelectric complexes and slow wave contractions. Immunohistochemistry of EAE colons exhibited a significant reduction in GFAP area of ENS ganglia, with no changes in HuD, S100, or neuron numbers. To test whether antibodies in MS bind to ENS structures, we collected serum samples from MS patients with constipation and without constipation, and healthy control patients without constipation. Immunoreactivity was tested using indirect immunofluorescence by applying serum samples to guinea pig ENS tissue. MS serum exhibited significantly higher immunoreactivity against guinea pig ENS than control patients, which was particularly evident in MS patients who did not experience constipation. There was no significant difference in immunoreactivity between MS patients with and without constipation. Targets of human MS and mouse EAE serum include enteric glia and neurons. Taken together, these data validate EAE as a model for constipation in MS, and support the concept that this symptom involves changes within the neuromuscular system of the colon. EAE mice develop symptoms consistent with constipation that affects functional ENS networks and may result in structural or phenotypic changes at the cellular level. Serum immunoreactivity suggests that autoantibodies could play a role in the development of constipation in MS by targeting the ENS itself