Publications by authors named "Matthew E Downs"

Existing magnetic resonance imaging (MRI) reference objects, or phantoms, are typically constructed from simple liquid or gel solutions in containers with specific geometric configurations to enable multi-year stability. However, there is a need for phantoms that better mimic the human anatomy without barriers between the tissues. Barriers result in regions without MRI signal between the different tissue mimics, which is an artificial image artifact.

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Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons.

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Non-invasive brain stimulation using focused ultrasound has many potential applications as a research and clinical tool, including its incorporation as either an extracorporeal or implantable neural prosthetic. To this end, we investigated the effect of focused ultrasound (FUS) combined with systemically administered microbubbles on visual-motor decision-making behavior in monkeys. We applied FUS to the putamen in one hemisphere to open the blood-brain barrier (BBB), and then tested behavioral performance 3-4 h later.

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Drug delivery to subcortical regions is susceptible to the blood-brain barrier (BBB) impeding the molecular exchange between the blood stream and the brain parenchyma. Focused ultrasound (FUS) coupled with the administration of microbubbles has been proved to open the BBB locally, transiently, and noninvasively both in rodents and in nonhuman-primates (NHPs). The development of this disruption technique independent of MRI monitoring is of primordial importance yet restrained to the targeting optimization.

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Over the past fifteen years, focused ultrasound coupled with intravenously administered microbubbles (FUS) has been proven an effective, non-invasive technique to open the blood-brain barrier (BBB) in vivo. Here we show that FUS can safely and effectively open the BBB at the basal ganglia and thalamus in alert non-human primates (NHP) while they perform a behavioral task. The BBB was successfully opened in 89% of cases at the targeted brain regions of alert NHP with an average volume of opening 28% larger than prior anesthetized FUS procedures.

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Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months.

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We have developed a bioinstrumentation course that emphasizes practical application of engineering and biological concepts by having students focus on the development of a single biomedical device: a cardiac pacemaker. In creating their benchtop pacemaker, students learn about and design sensing circuitry, data acquisition and processing code, control system algorithms, and stimulation electronics. They also gain an understanding of cardiac anatomy and electrophysiology.

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Molecular shuttles powered by kinesin motors require guiding tracks to perform specific tasks in nanoscale devices. Here, using our simulation of molecular shuttle movements, we describe an in silico evolutionary design method that makes it possible to automatically design the guiding tracks in accordance with their functions defined by designers. With this design method, we designed two types of pre-existing guiding track modules with improved performances, as well as one with a novel function.

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In this study we have developed a novel model of the deflection of primary cilia experiencing fluid flow accounting for phenomena not previously considered. Specifically, we developed a large rotation formulation that accounts for rotation at the base of the cilium, the initial shape of the cilium and fluid drag at high deflection angles. We utilised this model to analyse full 3D data-sets of primary cilia deflecting under fluid flow acquired with high-speed confocal microscopy.

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The primary cilium is a non-motile singular cellular structure that extends from the surface of nearly every cell in the body. The cilium has been shown to play numerous roles in maintaining tissue homeostasis, through regulating signaling pathways and sensing both biophysical and biochemical changes in the extracellular environment. The structural performance of the cilium is paramount to its function as defective cilia have been linked to numerous pathologies.

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