Nanoparticle Neuromodulation

The current standards for whole-brain in vivo imaging cannot provide the resolution and neuron stimulation needed to study neuronal plasticity. Current in vivo studies of neuronal dynamics are limited to animal models, due to the deleterious effects of fluorophores. Nanoparticle quantum dots (QDs) are a promising alternative to traditional fluorophores. QDs have properties that can elicit electrical activity in neurons. Scientists at the University of Nova Gorica are studying this interaction. We designed a perfusion system to deliver drugs and QDs to neuron cultures. Using this device, and calcium imaging techniques, we demonstrated that the mechanism of interaction between carboxyl-coated QDs and hippocampal neurons is localized to the synapse, producing synchronous electrical activity

Design and development of a pulsatile axial flow blood pump as a left ventricular assist device

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonEach year all over the world, Millions of patients from infants to adults are diagnosed with heart failure. A limited number of donor hearts available for these patients results in a tremendous demand of mechanical circulatory support (MCS) system, either in the form of total artificial heart (TAH) or a ventricular assist device (VAD). Physiologically MCS are expected to provide heart; a time to rest and potential recovery by unloading the ventricle, while maintaining the adequate peripheral as well as coronary circulation. Existing ventricular assist devices (VAD) have employed either displacement type pulsatile flow pumping systems or continuous flow type centrifugal/rotodynamic pumps systems. Displacement type devices produce a pulsatile outflow, which has significant benefits on vital organ function and end organ recovery. Continuous flow devices are small and can be placed within body using minimal invasive procedures, in addition they reduces infection as well as mechanical failure related complications. Despite availability of success stories for both types of pumping systems, the selection of the either of them is an ongoing debate. This thesis aims to merge the advantages of displacement pumps (pulsatile flow) and axial-flow pumps (continuous flow) into a novel left vertical assist device (LVAD), by designing a novel minimal invasive, miniature axial-flow pump producing pulsating outflow for the patients having early heart failure and myocardial infarction as a Bridge-To-Recovery (BTR) or Bridge-To-Decision (BTD) device. The design of VAD, the experimental setup and dedicated control system were developed for the in vitro evaluation of pulsatile flow. Computational fluid dynamics (CFD) had been employed for the detail investigation of pulsatile flow. In addition, CFD was also applied to optimize the pulse generation for low haemolysis levels. Outcome of the study produces comprehensive understanding for the generation of pulsatile flow using an axial flow pump. Further, it provides the means of generating a controlled pulse that can regulate flow rate for varying heart rate within low haemolysis levels

A Numerical Study of the Scaling and Control of Crossing Shock-Wave/Turbulent Boundary-Layer Interactions

To improve the design process of hypersonic vehicles, the performance of high-speed inlets must be evaluated through their entire flight domain. Hypersonic inlets are optimized for cruise conditions, but off-design operation introduces significant sources of uncertainty. Although many studies of high-speed inlets exist, much work is still needed in understanding the uncertainty associated with extrapolating ground test data to true flight conditions. Many ground facilities can match flight Mach numbers; however, many of these facilities are limited in Reynolds number ranges and matching true flight temperatures is difficult without vitiating the air. To assist in understanding the uncertainty associated with these experimental complications, the present study conducted a numerical campaign observing the effects of scaling Reynolds number, stagnation temperature, and gas and wall thermal models on high-speed, crossing-shock-wave/boundary-layer interactions. The interaction was generated by two symmetric, sharp fins, and this geometry is intended to be representative of high-speed inlets. The primary flow feature observed was the distortion levels downstream of the interaction. Distortion is difficult to measure experimentally and is a commonly observed metric determining the performance of an inlet. It was found that distortion decreased with an increase in Reynolds number and compressible shape factor of the incoming flow. The performance of vortex generators in passively controlling this interaction was also studied. These devices were shown to delay separation, however they also increased distortion levels at the outlet, and induced momentum losses compared to the baseline case without flow control

Updates to Multi-Dimensional Flux Reconstruction for Hypersonic Simulations on Tetrahedral Grids

The quality of simulated hypersonic stagnation region heating with tetrahedral meshes is investigated by using an updated three-dimensional, upwind reconstruction algorithm for the inviscid flux vector. An earlier implementation of this algorithm provided improved symmetry characteristics on tetrahedral grids compared to conventional reconstruction methods. The original formulation however displayed quantitative differences in heating and shear that were as large as 25% compared to a benchmark, structured-grid solution. The primary cause of this discrepancy is found to be an inherent inconsistency in the formulation of the flux limiter. The inconsistency is removed by employing a Green-Gauss formulation of primitive gradients at nodes to replace the previous Gram-Schmidt algorithm. Current results are now in good agreement with benchmark solutions for two challenge problems: (1) hypersonic flow over a three-dimensional cylindrical section with special attention to the uniformity of the solution in the spanwise direction and (2) hypersonic flow over a three-dimensional sphere. The tetrahedral cells used in the simulation are derived from a structured grid where cell faces are bisected across the diagonal resulting in a consistent pattern of diagonals running in a biased direction across the otherwise symmetric domain. This grid is known to accentuate problems in both shock capturing and stagnation region heating encountered with conventional, quasi-one-dimensional inviscid flux reconstruction algorithms. Therefore the test problems provide a sensitive indicator for algorithmic effects on heating. Additional simulations on a sharp, double cone and the shuttle orbiter are then presented to demonstrate the capabilities of the new algorithm on more geometrically complex flows with tetrahedral grids. These results provide the first indication that pure tetrahedral elements utilizing the updated, three-dimensional, upwind reconstruction algorithm may be used for the simulation of heating and shear in hypersonic flows in upwind, finite volume formulations

Comprehensive 4D velocity mapping of the heart and great vessels by cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Phase contrast cardiovascular magnetic resonance (CMR) is able to measure all three directional components of the velocities of blood flow relative to the three spatial dimensions and the time course of the heart cycle. In this article, methods used for the acquisition, visualization, and quantification of such datasets are reviewed and illustrated.</p> <p>Methods</p> <p>Currently, the acquisition of 3D cine (4D) phase contrast velocity data, synchronized relative to both cardiac and respiratory movements takes about ten minutes or more, even when using parallel imaging and optimized pulse sequence design. The large resulting datasets need appropriate post processing for the visualization of multidirectional flow, for example as vector fields, pathlines or streamlines, or for retrospective volumetric quantification.</p> <p>Applications</p> <p>Multidirectional velocity acquisitions have provided 3D visualization of large scale flow features of the healthy heart and great vessels, and have shown altered patterns of flow in abnormal chambers and vessels. Clinically relevant examples include retrograde streams in atheromatous descending aortas as potential thrombo-embolic pathways in patients with cryptogenic stroke and marked variations of flow visualized in common aortic pathologies. Compared to standard clinical tools, 4D velocity mapping offers the potential for retrospective quantification of flow and other hemodynamic parameters.</p> <p>Conclusions</p> <p>Multidirectional, 3D cine velocity acquisitions are contributing to the understanding of normal and pathologically altered blood flow features. Although more rapid and user-friendly strategies for acquisition and analysis may be needed before 4D velocity acquisitions come to be adopted in routine clinical CMR, their capacity to measure multidirectional flows throughout a study volume has contributed novel insights into cardiovascular fluid dynamics in health and disease.</p

Circulation and Transport Timescales in Tidally Dominated Estuaries

The susceptibility of estuaries to pollution has increased in the past few decades due to the increased anthropogenic inputs. The vulnerability of these estuaries to pollution is closely related to the circulation and transport in these estuaries. This work, therefore, aims to understand the transport of water-born materials in tidally dominated estuaries in relation to residual circulation and estuarine shape. The role of river discharge, tide, density gradient, and advection in altering the residual circulation and the transport timescales (flushing and residence time) are investigated. Three-dimensional hydrodynamic Eulerian-Lagrangian models are developed considering mesotidal (2 m 4 m) estuaries as the tidal could be significant compared to the mean flow. The Frenchman Bay (a mesotidal) in Maine, USA, and The Gironde estuary (macrotidal) in France are considered as study sites. The results show that density gradient and river discharge can be an important driver for the residual circulation and the flushing in wide estuaries with relatively simple geometry (simple bed profile and no constriction, headlands, or island). The results also demonstrate that the density gradient is more important to the transport than the river discharge in mesotidal estuaries and the river discharge is more important than the density gradient in macrotidal estuaries due to the increase of friction. The presence of complex morphological features gives arise for the advection to drive the residual circulation in estuaries and may affect the transport timescale. It is shown that advection can decrease the flushing time by 100% at the location where advection dominates the creation of residual circulation. It is shown that the residual circulation can be complex. Regardless of the complexity of the flow in estuaries, it is demonstrated that it is possible to predict what mechanism (river, tide, density gradient) drive the transport process in estuaries and whether to expect high or low flushing time based on simple metrics such as estuarine width and tidal excursion (the distance traveled by a water parcel over half tidal cycle). Such knowledge can facilitate better water-quality management as it provides a general idea about the transport and the water quality in estuarine environments

Atrioventricular septal defect : advanced imaging from early development to long-term follow-up

The aim of this thesis is to review the current knowledge on atrioventricular septal defect (AVSD) (Part 1), to study the pathogenesis of AVSD (Part 2) and finally to analyze cardiac outcome long-term after AVSD correction (Part 3). Studies are performed with novel imaging techniques. In part 2 it is made plausible that AVSD is a sliding scale and that patients with Down syndrome without AVSD also have abnormalities of the membranous septum and atrioventricular valves. High frequency ultrasound in mouse embryos shows to be a promising technique to study cardiovascular flow in early stages of heart development. In a mouse model with disturbed VEGF signalling, the heart rate is reduced and the sinoatrial node develops abnormally. Finally, in part 3 of this thesis, 4DFlow MRI data reveals that patients with an abnormal left atrioventricular valve (LAVV) after AVSD correction have aberrant intra-cardiac flow patterns. During diastole the inflow into the left ventricle is directed more towards the lateral wall, more towards the apex and vortex formation is abnormal. During systole the dynamic and eccentric regurgitation of the LAVV disturbs the normal recirculating flow patterns in the left atrium.4DFlow MRI can be used to reliably quantify flow over the LAVV.UBL - phd migration 201

혈관 구조 분석 기반 혈류선 추출과 불투명도 변조를 이용한 혈류 가시화 기법

학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2016. 2. 신영길.With recent advances in acquisition and simulation of blood flow data, blood flow visualization has been widely used in medical imaging for the diagnosis and treatment of pathological vessels. The integral line based method has been most commonly employed to depict hemodynamic data because it exhibits a long term flow behavior useful for flow analysis. This method generates integral lines to be used as a basis for graphical representation by tracing the trajectory of a massless particle released on the vector field through a numerical integration. However, there are several unsolved problems when this previous method is applied to thin curved vascular structures. The first one is to locate a seeding plane, which is manually performed in the existing methods, thus yielding inconsistent visual results. The second one is the early termination of a line integration due to locally reversed flow and narrow tubular structure, which results in short flowlines comparing with the vessel length. And the last one is the line occlusion caused by the dense depiction of flowlines. Additionally, in blood flow visualization for clinical uses, it is essential to apparently exhibit abnormal flow relevant to vessel diseases. In this paper, we present an enhanced method that overcomes problems related to the integration based flow visualization and depicts hemodynamics in a more informative way for assisting the diagnosis process. Using the fact that blood flow passes through the inlet or outlet but is blocked by vessel wall, we firstly identify the vessel inlet or outlet by the orthogonality metric between flow velocity vector and vessel surface normal vector. Then, we generate seed points on the detected inlet or outlet by Poisson disk sampling. Therefore, we can achieve the automatic seeding that leads to a consistent and faster flow depiction by skipping the manual location of a seeding plane to initiate the line integration. In addition, we resolve the early terminated line integration by applying the tracing direction adaptively based on flow direction at each seed point and by performing the additional seeding near the terminated location. This solution enables to yield length-extended flowlines, which contribute to faithful flow visualization. Based on the observation that blood flow usually follows the vessel track if there is no obstacle or leak in the middle of a passage, we define the representative flowline for each branch by the vessel centerline. Then, we render flowlines by assigning the opacity according to their shape similarity with the vessel centerline so that flowlines similar to the vessel centerline are shown transparently, while different ones opaquely. Accordingly, our opacity modulation method enables flowlines with unusual flow pattern to appear more noticeable, while minimizing visual clutter and line occlusion. Finally, we introduce HSV (hue, saturation, value) color coding to simultaneously exhibit flow attributes such as local speed and residence time. This color coding gives a more realistic fading effect on the older particles or line segments by attenuating the saturation according to the residence time. Hence, it supports users in comprehending intuitively multiple information at once. Experimental results show that our technique is well suitable to depict blood flow in vascular structures.Chapter 1 Introduction 1 1.1 Motivation 1 1.2 Problem Statement 3 1.3 Main Contribtion 7 1.4 Organization of the Dissertation 8 Chapter 2 Related Works 9 2.1 Flow and Velocity Vector 9 2.2 Flow Visualization 10 2.3 Blood Flow Visualization 16 2.3.1 Geometric Method 16 2.3.2 Feature-Based Method 18 2.3.3 Partition-Based Method 19 Chapter 3 Integration based Flowline Extraction 22 3.1 Overview 22 3.2 Seeding 23 3.3 Barycentric Coordinate Conversion 24 3.4 Cell Searching 26 3.5 Velocity Vector Calculation 27 3.6 Advection 28 3.7 Step Size Adaptation 30 Chapter 4 Blood Flow Visualization using Flow and Geometric Analysis 32 4.1 Preprocessing 33 4.2 Inlet or Outlet based Seeding 35 4.3 Tracing 39 4.3.1 Flow based Bidirectional Tracing 39 4.3.2 Additional Seeding for Length Extended Line Integration 41 4.4 Opacity Modulation 43 4.4.1 Global Opacity 45 4.4.2 Local Opacity 46 4.4.3 Opacity Adjustment 52 4.4.4 Blending 53 4.5 HSV Color Coding 54 4.6 Vessel Rendering 58 4.6.1 Vessel Smoothing 59 4.6.2 Vessel Contour Enhancement 60 4.7 Flowline Drawing 61 4.7.1 Line Illumination 61 4.7.2 Line Halo 63 4.8 Animation 64 Chapter 5 Experimental Results 67 5.1 Evaluation on Seeding 69 5.2 Evaluation on Tracing 74 5.3 Evaluation on Opacity Modulation 82 5.4 Parameter Study 85 Chapter 6 Conclusion 87 Bibliography 89 초 록 99Docto