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Worthington A.,Ryerson University | Peng P.,University of Toronto | Rod K.,University of Toronto | Bril V.,University of Western Ontario | And 2 more authors.
IEEE Journal of Translational Engineering in Health and Medicine | Year: 2016

High intensity focused ultrasound (HIFU) is a form of thermal ablation technique which can treat a variety of medical afflictions. One promising therapeutic use is the permanent destruction of nerves non-invasively in patients with severe spasticity or certain types of pain (e.g. phantom limb pain). To this end, HIFU requires ultrasound guidance which allows the non-invasive, target-specific deposition of thermal energy to the targeted nerve thereby blocking axonal conduction. In this work, a composite system comprising both ultrasound-imaging and HIFU therapy was developed and used to induce localized non-invasive nerve blockage in an in vivo large animal study. Five pigs were used with the femoral nerve as the target. Calibrated needle thermocouples inserted at the target site were employed to monitor the target tissue temperature. The degree of nerve blockage was assessed by measuring compound action potential (CAP) signal with a clinical nerve electrophysiology system before and after HIFU exposures. An average CAP signal amplitude reduction of 49% of baseline with a standard deviation of 9% was observed after 20-30 minutes post exposure. These results demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a potential non-invasive nerve ablation method. © 2013 IEEE.


Fernandez-Rodriguez M.A.,University of GranadaGranada | Ramos J.,University of the Basque Country | Ramos J.,Institute for Biomedical Engineering | Isa L.,ETH Zurich | And 3 more authors.
Langmuir | Year: 2015

Surface heterogeneity affects the behavior of nanoparticles at liquid interfaces. To gain a deeper understanding on the details of these phenomena, we have measured the interfacial activity and contact angle at water/decane interfaces for three different types of nanoparticles: homogeneous poly(methyl methacrylate) (PMMA), silica functionalized with a capping ligand containing a methacrylate terminal group, and Ag-based Janus colloids with two capping ligands of different hydrophobicity. The interfacial activity was analyzed by pendant drop tensiometry, and the contact angle was measured directly by freeze-fracture shadow-casting cryo-scanning electron microscopy. The silver Janus nanoparticles presented the highest interfacial activity, compared to the silica nanoparticles and the homogeneous PMMA nanoparticles. Additionally, increasing the bulk concentration of the PMMA and silica nanoparticles up to 100-fold compared to the Janus nanoparticles led to silica particles forming fractal-like structures at the interface, contrary to the PMMA particles that did not show any spontaneous adsorption. © 2015 American Chemical Society.


Spescha R.D.,University of Zürich | Klohs J.,Institute for Biomedical Engineering | Semerano A.,San Raffaele Scientific Institute | Giacalone G.,San Raffaele Scientific Institute | And 21 more authors.
European Heart Journal | Year: 2015

Aim Constitutive genetic deletion of the adaptor protein p66Shc was shown to protect from ischaemia/reperfusion injury. Here,we aimed at understanding the molecular mechanisms underlying this effect in stroke and studied p66Shc gene regulation in human ischaemic stroke. Methods and results Ischaemia/reperfusion brain injury was induced by performing a transient middle cerebral artery occlusion surgery on wild-type mice. After the ischaemic episode and upon reperfusion, small interfering RNA targeting p66Shcwas injected intravenously. We observed that post-ischaemic p66Shc knockdown preserved blood-brain barrier integrity that resulted in improved stroke outcome, as identified by smaller lesion volumes, decreased neurological deficits, and increased survival. Experiments on primary human brain microvascular endothelial cells demonstrated that silencing of the adaptor protein p66Shc preserves claudin-5 protein levels during hypoxia/reoxygenation by reducing nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. Further, we found that in peripheral blood monocytes of acute ischaemic stroke patients p66Shc gene expression is transiently increased and that this increase correlates with short-term neurological outcome. Conclusion Post-ischaemic silencing of p66Shc upon reperfusion improves stroke outcome in mice while the expression of p66Shcgene correlates with short-term outcome in patients with ischaemic stroke. © The Author 2015.


Bok T.-H.,Ryerson University | Bok T.-H.,Institute for Biomedical Engineering | Hysi E.,Ryerson University | Hysi E.,Institute for Biomedical Engineering | And 2 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2016

This paper attempts to experimentally and analytically quantify the aggregation-induced changes in the photoacoustic amplitude (PAA) by simultaneously examining the effect of red blood cell (RBC) aggregate size and optical illumination wavelength. In experiments, the pulsatile flow of human whole blood at 60 bpm was imaged using the VevoLAZR system equipped with a 40-MHz-linear-array probe. The samples were illuminated every 10 nm from 700 to 900 nm. For the analytical model, the PAA from both a collection of randomly distributed RBCs of 5, 10, 15, 20, 25, and 30 cells and a single absorber as a spherical aggregate of RBCs formed by the corresponding number of RBCs. The oxygen saturation (sO2) was measured as 74% and 80% for the non-aggregated RBCs and the RBC aggregation. These values were assigned to the analytical RBC aggregates containing between 5 and 30 cells. The normalized PAA (nPAA) for the experimental results was compared to that generated by the theoretical calculations. At a given wavelength, the analytical nPAA for the collection of RBCs were identical for all numbers of RBCs, but that for the RBC aggregate increased with the number of RBCs forming the aggregate due to the increase in the effective photoacoustic absorber size. The experimental as well as analytical nPAA for both RBC aggregation and non-aggregation increased with the wavelength at a given absorber size. This was due to the fact that the PAA is mainly determined by the optical absorption coefficient (μa) which increases due to the relationship between and wavelength. In addition, the difference of PAA between RBC aggregation and nonaggregation also increased with the wavelength due to the increase in the μa induced by the hypothesized enhanced sO2 resulting from the increased size of RBC aggregates. These results can be used as a means of estimating the oxygen loading and unloading during blood flow. This investigation elucidates the quantitative relationship between the RBC aggregate size and the optical illumination wavelength for probing the physiology of flowing blood. © 2016 SPIE.


Thuring T.,Paul Scherrer Institute | Thuring T.,Institute for Biomedical Engineering | Hammerle S.,SCANCO Medical AG | Weiss S.,SCANCO Medical AG | And 6 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2013

Today's commercial X-ray micro computed tomography (CT) specimen systems are based on microfocus sources, 2D pixel array cameras and short source-to-detector distances (i.e. cone-beam configurations). High resolution is achieved by means of geometric magnification. The further development of such devices to acquire phase and scattering contrast images can dramatically enhance their range of applications. Due to the compact geometries, which imply a highly diverging beam, the gratings must be curved to maintain highest imaging performance over a large field of view. We report about the implementation of extremely compact Talbot and Talbot- Lau type grating interferometers which are compatible to the geometry of typical micro CT systems. For the analytical description of the imaging system, formulas are presented describing the dependency of the sensitivity on geometric parameters, camera and source parameters. Further, the imaging pipeline consisting of the data acquisition protocol, radiographic phase retrieval and tomographic image reconstruction is illustrated. The reported methods open the way for an immediate integration of phase and scattering contrast imaging on table top X-ray micro CT scanners. © 2013 SPIE.


Schmitt K.-U.,Institute for Biomedical Engineering | Schlittler M.,ETH Zurich | Boesiger P.,Institute for Biomedical Engineering
Journal of Sports Sciences | Year: 2010

There is a risk of hip injury in dives to the side by soccer goalkeepers. In this study, we assessed hip loading in goalkeepers when performing such dives. The experiments were conducted in a laboratory setting using an in-ground force plate as well as on a grass surface when the athletes were equipped with force sensors. The forces acting on the hip were measured and high-speed video analysis was performed, allowing the investigation of the dive characteristics and techniques. The peak force values recorded in the laboratory setting ranged from 3 to 8 kN, which corresponded to 4.2-8.6 times body weight. The vertical impact velocities reached 3.25 m · s-1. In the field experiments, a hip loading of 87-183 N · cm-2 was determined. We found that goalkeepers who perform a rolling motion reduce their hip loading. The data provided by this study add to the biomechanics database and contribute to the establishment of injury criteria. Such information is necessary to develop and implement strategies to help prevent hip injuries. © 2010 Taylor & Francis.


Todorova N.,RMIT University | Chiappini C.,Institute for Biomedical Engineering | Mager M.,Institute for Biomedical Engineering | Simona B.,Institute for Biomedical Engineering | And 3 more authors.
Nano Letters | Year: 2014

Functionalizing nanoparticles with cell-penetrating peptides is a popular choice for cellular delivery. We investigated the effects of TAT peptide concentration and arrangement in solution on functionalized nanoparticles' efficacy for membrane permeation. We found that cell internalization correlates with the positive charge distribution achieved prior to nanoparticle encountering interactions with membrane. We identified a combination of solution based properties required to maximize the internalization efficacy of TAT-functionalized nanoparticles. © 2014 American Chemical Society.


News Article | December 2, 2016
Site: www.rdmag.com

Scientists have developed a highly sensitive sensor to detect tiny changes in strong magnetic fields. The sensor may find widespread use in medicine and other areas. Researchers from the Institute for Biomedical Engineering, which is operated jointly by ETH Zurich and the University of Zurich, have succeeded in measuring tiny changes in strong magnetic fields with unprecedented precision. In their experiments, the scientists magnetised a water droplet inside a magnetic resonance imaging (MRI) scanner, a device that is used for medical imaging. The researchers were able to detect even the tiniest variations of the magnetic field strength within the droplet. These changes were up to a trillion times smaller than the seven tesla field strength of the MRI scanner used in the experiment. "Until now, it was possible only to measure such small variations in weak magnetic fields," says Klaas Prüssmann, Professor of Bioimaging at ETH Zurich and the University of Zurich. An example of a weak magnetic field is that of the Earth, where the field strength is just a few dozen microtesla. For fields of this kind, highly sensitive measurement methods are already able to detect variations of about a trillionth of the field strength, says Prüssmann. "Now, we have a similarly sensitive method for strong fields of more than one tesla, such as those used, inter alia, in medical imaging." The scientists based the sensing technique on the principle of nuclear magnetic resonance, which also serves as the basis for magnetic resonance imaging and the spectroscopic methods that biologists use to elucidate the 3D structure of molecules. However, to measure the variations, the scientists had to build a new high-precision sensor, part of which is a highly sensitive digital radio receiver. "This allowed us to reduce background noise to an extremely low level during the measurements," says Simon Gross. Gross wrote his doctoral thesis on this topic in Prüssmann's group and is lead author of the paper published in the journal Nature Communications. In the case of nuclear magnetic resonance, radio waves are used to excite atomic nuclei in a magnetic field. This causes the nuclei to emit weak radio waves of their own, which are measured using a radio antenna; their exact frequency indicates the strength of the magnetic field. As the scientists emphasise, it was a challenge to construct the sensor in such a way that the radio antenna did not distort the measurements. The scientists have to position it in the immediate vicinity of the water droplet, but as it is made of copper it becomes magnetised in the strong magnetic field, causing a change in the magnetic field inside the droplet. The researchers therefore came up with a trick: they cast the droplet and antenna in a specially prepared polymer; its magnetisability (magnetic susceptibility) exactly matched that of the copper antenna. In this way, the scientists were able to eliminate the detrimental influence of the antenna on the water sample. This measurement technique for very small changes in magnetic fields allows the scientists to now look into the causes of such changes. They expect their technique to find use in various areas of science, some of them in the field of medicine, although the majority of these applications are still in their infancy. "In an MRI scanner, the molecules in body tissue receive minimal magnetisation - in particular, the water molecules that are also present in blood," explains doctoral student Gross. "The new sensor is so sensitive that we can use it to measure mechanical processes in the body; for example, the contraction of the heart with the heartbeat." The scientists carried out an experiment in which they positioned their sensor in front of the chest of a volunteer test subject inside an MRI scanner. They were able to detect periodic changes in the magnetic field, which pulsated in time with the heartbeat. The measurement curve is reminiscent of an electrocardiogram (ECG), but unlike the latter measures a mechanical process (the contraction of the heart) rather than electrical conduction. "We are in the process of analysing and refining our magnetometer measurement technique in collaboration with cardiologists and signal processing experts," says Prüssmann. "Ultimately, we hope that our sensor will be able to provide information on heart disease - and do so non-invasively and in real time." The new measurement technique could also be used in the development of new contrast agents for magnetic resonance imaging: in MRI, the image contrast is based largely on how quickly a magnetised nuclear spin reverts to its equilibrium state. Experts call this process relaxation. Contrast agents influence the relaxation characteristics of nuclear spins even at low concentrations and are used to highlight certain structures in the body. In strong magnetic fields, sensitivity issues had previously restricted scientists to measurement of just two of the three spatial nuclear spin components and their relaxation. They had to rely on an indirect measurement of relaxation in the important third dimension. For the first time, the new high-precision measurement techniqueallows the direct measurement of all three dimensions of nuclear spin in strong magnetic fields. Direct measurement of all three nuclear spin components also paves the way for future developments in nuclear magnetic resonance (NMR) spectroscopy for applications in biological and chemical research.


News Article | December 2, 2016
Site: phys.org

Researchers from the Institute for Biomedical Engineering, which is operated jointly by ETH Zurich and the University of Zurich, have succeeded in measuring tiny changes in strong magnetic fields with unprecedented precision. In their experiments, the scientists magnetised a water droplet inside a magnetic resonance imaging (MRI) scanner, a device that is used for medical imaging. The researchers were able to detect even the tiniest variations of the magnetic field strength within the droplet. These changes were up to a trillion times smaller than the seven tesla field strength of the MRI scanner used in the experiment. "Until now, it was possible only to measure such small variations in weak magnetic fields," says Klaas Prüssmann, Professor of Bioimaging at ETH Zurich and the University of Zurich. An example of a weak magnetic field is that of the Earth, where the field strength is just a few dozen microtesla. For fields of this kind, highly sensitive measurement methods are already able to detect variations of about a trillionth of the field strength, says Prüssmann. "Now, we have a similarly sensitive method for strong fields of more than one tesla, such as those used, inter alia, in medical imaging." The scientists based the sensing technique on the principle of nuclear magnetic resonance, which also serves as the basis for magnetic resonance imaging and the spectroscopic methods that biologists use to elucidate the 3D structure of molecules. However, to measure the variations, the scientists had to build a new high-precision sensor, part of which is a highly sensitive digital radio receiver. "This allowed us to reduce background noise to an extremely low level during the measurements," says Simon Gross. Gross wrote his doctoral thesis on this topic in Prüssmann's group and is lead author of the paper published in the journal Nature Communications. In the case of nuclear magnetic resonance, radio waves are used to excite atomic nuclei in a magnetic field. This causes the nuclei to emit weak radio waves of their own, which are measured using a radio antenna; their exact frequency indicates the strength of the magnetic field. As the scientists emphasise, it was a challenge to construct the sensor in such a way that the radio antenna did not distort the measurements. The scientists have to position it in the immediate vicinity of the water droplet, but as it is made of copper it becomes magnetised in the strong magnetic field, causing a change in the magnetic field inside the droplet. The researchers therefore came up with a trick: they cast the droplet and antenna in a specially prepared polymer; its magnetisability (magnetic susceptibility) exactly matched that of the copper antenna. In this way, the scientists were able to eliminate the detrimental influence of the antenna on the water sample. This measurement technique for very small changes in magnetic fields allows the scientists to now look into the causes of such changes. They expect their technique to find use in various areas of science, some of them in the field of medicine, although the majority of these applications are still in their infancy. "In an MRI scanner, the molecules in body tissue receive minimal magnetisation - in particular, the water molecules that are also present in blood," explains doctoral student Gross. "The new sensor is so sensitive that we can use it to measure mechanical processes in the body; for example, the contraction of the heart with the heartbeat." The scientists carried out an experiment in which they positioned their sensor in front of the chest of a volunteer test subject inside an MRI scanner. They were able to detect periodic changes in the magnetic field, which pulsated in time with the heartbeat. The measurement curve is reminiscent of an electrocardiogram (ECG), but unlike the latter measures a mechanical process (the contraction of the heart) rather than electrical conduction. "We are in the process of analysing and refining our magnetometer measurement technique in collaboration with cardiologists and signal processing experts," says Prüssmann. "Ultimately, we hope that our sensor will be able to provide information on heart disease - and do so non-invasively and in real time." The new measurement technique could also be used in the development of new contrast agents for magnetic resonance imaging: in MRI, the image contrast is based largely on how quickly a magnetised nuclear spin reverts to its equilibrium state. Experts call this process relaxation. Contrast agents influence the relaxation characteristics of nuclear spins even at low concentrations and are used to highlight certain structures in the body. In strong magnetic fields, sensitivity issues had previously restricted scientists to measurement of just two of the three spatial nuclear spin components and their relaxation. They had to rely on an indirect measurement of relaxation in the important third dimension. For the first time, the new high-precision measurement technique allows the direct measurement of all three dimensions of nuclear spin in strong magnetic fields. Direct measurement of all three nuclear spin components also paves the way for future developments in nuclear magnetic resonance (NMR) spectroscopy for applications in biological and chemical research. Explore further: Improved nuclear magnetic resonance technique allows researchers to measure signals from a single molecule More information: Simon Gross et al, Dynamic nuclear magnetic resonance field sensing with part-per-trillion resolution, Nature Communications (2016). DOI: 10.1038/NCOMMS13702


News Article | December 2, 2016
Site: www.eurekalert.org

Researchers from the Institute for Biomedical Engineering, which is operated jointly by ETH Zurich and the University of Zurich, have succeeded in measuring tiny changes in strong magnetic fields with unprecedented precision. In their experiments, the scientists magnetised a water droplet inside a magnetic resonance imaging (MRI) scanner, a device that is used for medical imaging. The researchers were able to detect even the tiniest variations of the magnetic field strength within the droplet. These changes were up to a trillion times smaller than the seven tesla field strength of the MRI scanner used in the experiment. "Until now, it was possible only to measure such small variations in weak magnetic fields," says Klaas Prüssmann, Professor of Bioimaging at ETH Zurich and the University of Zurich. An example of a weak magnetic field is that of the Earth, where the field strength is just a few dozen microtesla. For fields of this kind, highly sensitive measurement methods are already able to detect variations of about a trillionth of the field strength, says Prüssmann. "Now, we have a similarly sensitive method for strong fields of more than one tesla, such as those used, inter alia, in medical imaging." The scientists based the sensing technique on the principle of nuclear magnetic resonance, which also serves as the basis for magnetic resonance imaging and the spectroscopic methods that biologists use to elucidate the 3D structure of molecules. However, to measure the variations, the scientists had to build a new high-precision sensor, part of which is a highly sensitive digital radio receiver. "This allowed us to reduce background noise to an extremely low level during the measurements," says Simon Gross. Gross wrote his doctoral thesis on this topic in Prüssmann's group and is lead author of the paper published in the journal Nature Communications. In the case of nuclear magnetic resonance, radio waves are used to excite atomic nuclei in a magnetic field. This causes the nuclei to emit weak radio waves of their own, which are measured using a radio antenna; their exact frequency indicates the strength of the magnetic field. As the scientists emphasise, it was a challenge to construct the sensor in such a way that the radio antenna did not distort the measurements. The scientists have to position it in the immediate vicinity of the water droplet, but as it is made of copper it becomes magnetised in the strong magnetic field, causing a change in the magnetic field inside the droplet. The researchers therefore came up with a trick: they cast the droplet and antenna in a specially prepared polymer; its magnetisability (magnetic susceptibility) exactly matched that of the copper antenna. In this way, the scientists were able to eliminate the detrimental influence of the antenna on the water sample. This measurement technique for very small changes in magnetic fields allows the scientists to now look into the causes of such changes. They expect their technique to find use in various areas of science, some of them in the field of medicine, although the majority of these applications are still in their infancy. "In an MRI scanner, the molecules in body tissue receive minimal magnetisation - in particular, the water molecules that are also present in blood," explains doctoral student Gross. "The new sensor is so sensitive that we can use it to measure mechanical processes in the body; for example, the contraction of the heart with the heartbeat." The scientists carried out an experiment in which they positioned their sensor in front of the chest of a volunteer test subject inside an MRI scanner. They were able to detect periodic changes in the magnetic field, which pulsated in time with the heartbeat. The measurement curve is reminiscent of an electrocardiogram (ECG), but unlike the latter measures a mechanical process (the contraction of the heart) rather than electrical conduction. "We are in the process of analysing and refining our magnetometer measurement technique in collaboration with cardiologists and signal processing experts," says Prüssmann. "Ultimately, we hope that our sensor will be able to provide information on heart disease - and do so non-invasively and in real time." The new measurement technique could also be used in the development of new contrast agents for magnetic resonance imaging: in MRI, the image contrast is based largely on how quickly a magnetised nuclear spin reverts to its equilibrium state. Experts call this process relaxation. Contrast agents influence the relaxation characteristics of nuclear spins even at low concentrations and are used to highlight certain structures in the body. In strong magnetic fields, sensitivity issues had previously restricted scientists to measurement of just two of the three spatial nuclear spin components and their relaxation. They had to rely on an indirect measurement of relaxation in the important third dimension. For the first time, the new high-precision measurement technique allows the direct measurement of all three dimensions of nuclear spin in strong magnetic fields. Direct measurement of all three nuclear spin components also paves the way for future developments in nuclear magnetic resonance (NMR) spectroscopy for applications in biological and chemical research. Gross S, Barmet C, Dietrich BE, Brunner DO, Schmid T, Prüssmann KP: Dynamic nuclear magnetic resonance field sensing with part-per-trillion resolution. Nature Communications, published online 2 December 2016, doi: 10.1038/NCOMMS13702

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