Establishing sheep as an experimental species to validate ultrasound-mediated blood-brain barrier opening for potential therapeutic interventions

Rationale: Treating diseases of the brain such as Alzheimer's disease (AD) is challenging as the blood-brain barrier (BBB) effectively restricts access of a large number of potentially useful drugs. A potential solution to this problem is presented by therapeutic ultrasound, a novel treatment modality that can achieve transient BBB opening in species including rodents, facilitated by biologically inert microbubbles that are routinely used in a clinical setting for contrast enhancement. However, in translating rodent studies to the human brain, the presence of a thick cancellous skull that both absorbs and distorts ultrasound presents a challenge. A larger animal model that is more similar to humans is therefore required in order to establish a suitable protocol and to test devices. Here we investigated whether sheep provide such a model. Methods: In a stepwise manner, we used a total of 12 sheep to establish a sonication protocol using a spherically focused transducer. This was assisted by ex vivo simulations based on CT scans to establish suitable sonication parameters. BBB opening was assessed by Evans blue staining and a range of histological tests. Results: Here we demonstrate noninvasive microbubble-mediated BBB opening through the intact sheep skull. Our non-recovery protocol allowed for BBB opening at the base of the brain, and in areas relevant for AD, including the cortex and hippocampus. Linear time-shift invariant analysis and finite element analysis simulations were used to optimize the position of the transducer and to predict the acoustic pressure and location of the focus. Conclusion: Our study establishes sheep as a novel animal model for ultrasound-mediated BBB opening and highlights opportunities and challenges in using this model. Moreover, as sheep develop an AD-like pathology with aging, they represent a large animal model that could potentially complement the use of non-human primates

A comparative study of electrical potential sensors and Ag/AgCl electrodes for characterising spontaneous and event related electroencephalagram signals

For exactly 90 years researchers have used electroencephalography (EEG) as a window into the activities of the brain. Even now its high temporal resolution coupled with relatively low cost compares favourably to other neuroimaging techniques such as magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). For the majority of this time the standard electrodes used for non-invasive monitoring of electrical activities of the brain have been Ag/AgCl metal electrodes. Although these electrodes provide a reliable method for recording EEG they suffer from noise, such as offset potential drift, and usability issues, for example, difficult skin preparation and cross-coupling of adjacent electrodes. In order to tackle these issues a prototype Electric Potential Sensor (EPS) device based on an auto-zero operational amplifier has been developed and evaluated. The absence of 1/f noise in these devices makes them ideal for use with signal frequencies of ~10 Hz or less. The EPS is a novel active ultrahigh impedance capacitively coupled sensor. The active electrodes are designed to be physically and electrically robust and chemically and biochemically inert. They are electrically insulated (anodized) and scalable. A comprehensive study was undertaken to compare the results of neural signals recorded by the EPS with a standard commercial EEG system. These studies comprised measurements of both free running EEG and Event Related Potentials (ERPs). Results demonstrate that the EPS provides a promising alternative, with many added benefits compared to standard EEG sensors, including reduced setup time, elimination of sensor cross-coupling, lack of a ground electrode and distortion of electrical potentials encountered when using standard gel electrodes. Quantitatively, highly similar signals were observed between the EPS and EEG sensors for both free running and evoked brain activity with cross correlations of higher than 0.9 between the EPS and a standard benchmark EEG system. Future developments of EPS-based neuroimaging include the implementation of a whole head ultra-dense EPS array, and the mapping of distributions of scalp recorded electrical potentials remotely

Computational fluid dynamics simulation and turbomachinery code validation of a high pressure ratio radial-inflow turbine

The present study explores reproducing the closest geometry of a high pressure ratio single stage radial-inflow turbine applied in the Sundstrans Power Systems T-100 Multipurpose Small Power Unit. The commercial software ANSYS-Vista RTD along with a built in module, BladeGen, is used to conduct a meanline design and create 3D geometry of one flow passage. Carefully examining the proposed design against the geometrical and experimental data, ANSYS-TurboGrid is applied to generate computational mesh. CFD simulations are performed with ANSYS-CFX in which three-dimensional Reynolds-Averaged Navier-Stokes equations are solved subject to appropriate boundary conditions. Results are compared with numerical and experimental data published in the literature in order to generate the exact geometry of the existing turbine and validate the numerical results against the experimental ones

Application of Metal Foams for Improving the Performance of Air-Cooled Heat Exchangers

This thesis investigates the application of metal foam heat exchangers to the air-cooled condensers of geothermal power plants in Australia where the resources are mostly located at the arid areas where there is no water for evaporative cooling of the power plant. One way to remove the heat from the thermodynamic cycles is to use (the most common) finned-tube heat exchangers, consisting of tubes with external fins to increase the air-side heat exchange surface. Another possible alternative is a class of designed porous materials called metal foams, containing such advantages as low-density, high area/volume ratio, and high strength structure. Therefore, they have been applied in a variety of industrial. The numerical study, in three main sections, has been conducted to explore that possibility. First, a comparison between the performance of a metal foam-wrapped solid cylinder in cross-flow and a commercially available finned-tune heat exchanger is investigated. Effects of the key parameters including the free-stream velocity and characteristics of metal foam such as porosity, permeability, and form drag coefficient on heat and fluid flow are examined. Being a determining factor in pressure drop and heat transfer increment, the porous layer thickness is changed systematically to observe that there is an optimum layer thickness beyond which the heat transfer does not improve while the pressure drop continues to increase. This has been verified by the application of Bejan’s Intersection of Asymptotes method. Results have been compared to those of a finned-tube heat exchanger to observe a higher area goodness factor for metal foam-wrapped cylinder. In the second part, an optimization study is carried out to discover an optimized design of metal foam heat exchangers as replacements for finned-tubes in air-cooled condensers of a geothermal power plant. Two different optimization techniques, based on first and second law (of thermodynamics) are reported. While the former leads to the highest heat transfer rate with as low pressure drop as possible, the latter minimizes the generated entropy in the thermodynamic system. Interestingly the two methods lead to the same optimal design. The new design has been compared to the conventional air-cooled condenser designed and optimized by using the commercially available software ASPEN. It is shown that while the heat transfer rate increases significantly (by an order of magnitude) compared to the finned tube for the same main flow obstruction height, the pressure drop increase is within an acceptable range. Further comparison between the two systems are carried out, making use of Mahjoob and Vafai's performance factor developed specifically for metal foam heat exchangers. Following that, the third part explores the heat transfer from a metal foam-wrapped tube bundle. Effects of key parameters, including the free stream velocity, longitudinal and transversal tube pitch, metal foam thickness and characteristics of the foam on heat and fluid flow are examined. It can be observed that the performance of the metal foam heat exchangers, measured in terms of area goodness factor, can be about four times better than that of the conventional design of finned-tube heat exchangers. It is also found that even a very thin layer of metal foam, when wrapped around a bare tube bundle, can significantly improve the area goodness factor. Finally, it is shown that while friction factor is more sensitive to the metal foam permeability than its porosity, the converse is true when it comes to the Colburn factor

Metal foam heat exchangers for thermal management of fuel cell systems

The present study explores the possibility of using metal foams for thermal management of fuel cells so that air-cooled fuel cell stacks can be commercialized as replacements for currently-available water-cooled counterparts. Experimental studies have been conducted to examine the heat transfer enhancement from a thin metal foam layer sandwiched between two bipolar plates of a cell. To do this, effects of the key parameters including the free stream velocity and characteristics of metal foam such as porosity, permeability, and form drag coefficient on heat and fluid flow are investigated. The improvements as a result of the application of metal foam layers on fuel cell systems efficiency have been analyzed and discussed. Non-optimized results have shown that to remove the same amount of generated heat, the air-cooled fuel cell systems using aluminum foams require half of the pumping power compared to water-cooled fuel cell systems

CFD simulation of a supercritical carbon dioxide radial-inflow turbine, comparing the results of using real gas equation of estate and real gas property file

The present study explores CFD analysis of a supercritical carbon dioxide (SCO2) radial-inflow turbine generating 100kW from a concentrated solar resource of 560oC with a pressure ratio of 2.2. Two methods of real gas property estimations including real gas equation of estate and real gas property (RGP) file - generating a required table from NIST REFPROP - were used. Comparing the numerical results and time consumption of both methods, it was shown that equation of states could insert a significant error in thermodynamic property prediction. Implementing the RGP table method indicated a very good agreement with NIST REFPROP while it had slightly more computational cost compared to the RGP table method.</jats:p