Pallav Kolli, Fabio Settecase, Matthew Amans und Robert Taylor von UCSF, Tim Roberts von der University of Pennsylvania Finanzierungsquellen NIH National Heart Lung Blood Institute (NHLBI) Award (M. Wilson): 1R01HL076486 American Society of Neuroradiologie Research and Education Foundation Scholar Award (S. Hetts) NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) Award (S. Hetts): 1R01EB012031

Ein. Mikrospule Fabrication <ol><li> Erhalt eines handelsüblichen Mikrokatheter (zB 2.3F Rapid Transit Cordis Neurovaskuläre Katheter, Raynham, MA) für ein Substrat. </li><li> Stellen Sie sicher, Kathetern haben keine Eisen-Komponenten werden als MR-Safe und liegen in der Größenordnung von 2,3 bis 3,0 F. </li><li> Sputter eine Titanhaftschicht durch eine Kupferkeimschicht zu einer 1 bis 2 mm OD Isolierrohr gefolgt. Mögliche Materialien sind Polyimid oder Aluminiumoxid (Ortech Advanced Ceramics, Sacramento, CA). </li><li> Elektrolytisch eine positive Photoresistschicht unter Verwendung Shipleys PEPR-2400 (derzeit von DOW Chemical unter der Bezeichnung Intervia 3D-P verkauft). Elektrotauchlackier ergibt sich eine gleichmäßige Beschichtung auf der nicht-planaren Zylinderfläche. </li><li> Fotolack wird durch eine einzigartige Laser-Direkt-write (Laser Drehmaschine, eine nicht-kommerzielle System am Lawrence Livermore National Laboratory entwickelt wurde) in dem Muster des gewünschten Spulenform (2A) ausgesetzt. Dies ist eine Modifikationtion der Technik ursprünglich in Malba et al. 14 </li><li> Entwickeln des belichteten Photoresists in einer 1% igen Lösung von Kaliumcarbonat bei 35 ° C. </li><li> Kupfer wird durch die verbleibende Resistmaske elektroplattiert, um das gewünschte Wicklung zu bilden. Das System kann herzustellen sowohl Magnet-und Helmholtz (Rennstrecke) Kupfer Muster (2C und 2D). </li><li> Nach Kupfer Elektroabscheidung, entfernen Sie das mit heißem Entwickler widerstehen. Entfernen Sie die Kupferkeimschicht durch die Titanhaftschicht gefolgt. </li><li> Befestigen Sie den Isolierschlauch der Katheterspitze mit Schrumpffolie, um die Montage zu vervollständigen. Stellen Sie sicher, dass die Schrumpffolie die gesamte coiled Spitze abdeckt. Zu mehrachsigen Kathetern zusammenzubauen platzieren Isolierrohr Strukturen ineinander wie in 2E gezeigt. </li><li> Faden Kupferdrähte durch das Lumen des Mikrokatheters und Lot zu den Spulen an der Spitze. </li><li> Ändern und verkürzen 6 ft RJ11 Telefonkabel to 3 m Länge. </li><li> Verbinden der Kupferdrähte, die aus dem hinteren Ende des Mikrokatheters Nabe zu dem modifizierten 3 ft Telefonbuchse Übertragungsleitung. </li></ol> 2. Wasserbad-Setup <ol><li> Ein kleines Loch in der Mitte der Seite einer Kunststoffwanne etwa 5 cm von der Unterseite. </li><li> Legen Sie eine 9F Avanti Cordis Gefäßscheide (Cordis Endovascular, Miami Lakes, FL) durch das Loch. </li><li> Schneiden die distale Spitze des Gefäßscheide Verlassen einer 4 cm langes Stück der sich in dem Becken. </li><li> Am Ende der Hülle, befestigen eines rotierenden oder hämostatischen Thuoy-Borst-Ventil, um den Ort des Mikrokatheters stabilisieren. </li><li> Füllen Sie das Becken mit destilliertem Wasser gewährleistet vollständiges Untertauchen des Geräts. </li><li> Legen Sie den Katheter mit coiled Spitze durch die Gefäßscheide und Ventil. </li><li> Messen und notieren die hemmungslose Länge der Mikrokatheter sich von dem Ventil in dem Wasserbad. </li><li> Legen Sie das Wasserbad mit MikroKathetersystem innerhalb des Magneten der MR-Scanner und zu orientieren bezüglich der Bohrung des Magneten. </li><li> Schließen Sie die geänderte 3 ft Telefonkabel an den Katheter zu einem 25 ft RJ11 Telefonkabel Übertragungsleitung mit einem 2-Wege-Klinkenbuchse. </li><li> Schließen Sie das andere Ende des 25 ft Telefonkabel zu einem Lambda LPD-422A-FM-Doppeltuner geregelte Stromversorgung zu liefern bis zu 1 A Strom an das Gerät. </li><li> Platzieren Sie die Übertragungsleitungen durch einen Wellenleiter und der Stromquelle außerhalb des MR-Scanners Raum außerhalb des 5 Gauss-Linie. </li></ol> 3. Schiff Phantom-Setup <ol><li> Konstruieren Sie eine hohles Gefäß Phantom mit einem Y-förmigen Kreuzung aus Gummischlauch vor den Experimenten. </li><li> Füllen Sie den Behälter Phantom mit einer 0,0102 M Lösung von Gadopentetatdimeglumin (GdDTPA) (Magnevist, Bayer Healthcare Pharmaceuticals, Montville, New Jersey) in destilliertem Wasser, um den Kontrast zwischen dem Phantom Schiffe und Hintergrund zu schaffen. </li><li> Montieren Sie den MicroCAtheter System wie in den Schritten 1,1 bis 1,9 skizziert. Verbinden des Katheters mit der Stromversorgung und der Position, wie in Schritten von 2,9 bis 2,11 beschrieben. </li><li> Positionieren Sie die Spitze des Mikrokatheters am Boden des Gefäßes Öffnung. </li><li> Platzieren des Phantoms innerhalb des Magneten des MR-Scanners und orientieren bezüglich der Bohrung des Magneten. </li></ol> 4. Magnetic Resonance Imaging <ol><li> Führen Bildgebung mit einem 1.5T klinischen MR-System (Siemens Avanto, SW: Syngo B13, Erlangen, Deutschland; Philips Achieva, SW Release 2.1, Cleveland, OH). </li><li> Übernehmen &lt;50 mA Strom, um die Katheterspitze Position zu visualisieren. Unter MRT, wird ein kleines magnetisches Moment an der Katheterspitze hergestellt werden, um eine deutliche Artefakt unterschiedlicher Form abhängig von dem Spulen erregt werden visualisieren. </li><li> Bewerben variable Mengen an Strom im Bereich von ± 100 mA aus dem Lambda duale Stromzufuhr zu den Spulen und beobachten Auslenkung der Spitze (3A-3C) im Wasser bath-Setup. Da Auslenkung der Spitze ist fast augenblicklich, müssen Strom nur für ~ 1-2 angewendet werden Sek. maximale Durchbiegung zu visualisieren. </li><li> Wiederholen und aufzeichnen aufeinanderfolgenden Anwendungen gesetzt Strommengen. </li><li> Wiederholen Sie Schritt 4,2 und gleichzeitig schieben Sie den Katheter per Hand ermöglicht mechanische Weiterentwicklung durch das Gefäß Phantom (4A und 4B). Anwenden an der Verzweigungsstelle Stroms, um die Katheterspitze in das gewünschte Gefäß abzulenken. Vorzurücken des Katheters in das Zweiggefäß durch manuelles Drücken des Katheterende (4C). Zurückziehen des Katheters an der Gefäßverzweigung und Wiederholung in der gegenüberliegenden Zweig (4D). </li><li> MR-Bilder zu erwerben Verwendung eines 2D Snapshot-FLASH-Sequenz (TR = 30 msec, TE = 1,4 ms, eine Matrix von 256 x 128 und Flipwinkel ~ 30 °). </li></ol> 5. Deflection Messungen Analysieren und zu messen Winkel Auslenkungen aufgenommenen Bilder währendWasserbad Experimente mit verschiedenen EDV-Anwendungen (alle Digital Imaging and Communications in Medicine (DICOM) Viewer).

<ol>
	<li>Molyneux, A. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=International+subarachnoid+aneurysm+trial+(ISAT)+of+neurosurgical+clipping+versus+endovascular+coiling+in+2143+patients+with+ruptured+intracranial+aneurysms:+a+randomised+comparison+of+effects+on+survival,+dependency,+seizures,+rebleeding,+subgroups,+and+aneurysm+occlusion.">International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion.</a> Lancet. 366, 809-817 (2005).</li><li>Razavi, M. K., Hwang, G., Jahed, A., Modanlou, S., Chen, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abdominal+myomectomy+versus+uterine+fibroid+embolization+in+the+treatment+of+symptomatic+uterine+leiomyomas.">Abdominal myomectomy versus uterine fibroid embolization in the treatment of symptomatic uterine leiomyomas.</a> AJR Am. J. Roentgenol. 180, 1571-1575 (2003).</li><li>Hoffman, S. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+meta-analysis+of+randomized+controlled+trials+comparing+coronary+artery+bypass+graft+with+percutaneous+transluminal+coronary+angioplasty:+one-+to+eight-year+outcomes.">A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes.</a> J. Am. Coll. Cardiol. 41, 1293-1304 (2003).</li><li>McDougall, C. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Causes+and+management+of+aneurysmal+hemorrhage+occurring+during+embolization+with+Guglielmi+detachable+coils.">Causes and management of aneurysmal hemorrhage occurring during embolization with Guglielmi detachable coils.</a> J. Neurosurg. 89, 87-92 (1998).</li><li>Willinsky, R. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurologic+complications+of+cerebral+angiography:+prospective+analysis+of+2,899+procedures+and+review+of+the+literature.">Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature.</a> Radiology. 227, 522-528 (2003).</li><li>Veith, F. J., Marin, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endovascular+technology+and+its+impact+on+the+relationships+among+vascular+surgeons,+interventional+radiologists,+and+other+specialists.">Endovascular technology and its impact on the relationships among vascular surgeons, interventional radiologists, and other specialists.</a> World J. Surg. 20, 687-691 (1996).</li><li>Miller, D. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+radiation+management+for+fluoroscopically+guided+interventional+procedures.">Clinical radiation management for fluoroscopically guided interventional procedures.</a> Radiology. 257, 321-332 .</li><li>Balter, S., Hopewell, J. W., Miller, D. L., Wagner, L. K., Zelefsky, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluoroscopically+guided+interventional+procedures:+a+review+of+radiation+effects+on+patients'+skin+and+hair.">Fluoroscopically guided interventional procedures: a review of radiation effects on patients' skin and hair.</a> Radiology. 254, 326-341 (2010).</li><li>Wagner, L. K., McNeese, M. D., Marx, M. V., Siegel, E. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Severe+skin+reactions+from+interventional+fluoroscopy:+case+report+and+review+of+the+literature.">Severe skin reactions from interventional fluoroscopy: case report and review of the literature.</a> Radiology. 213, 773-776 (1999).</li><li>Koenig, T. R., Wolff, D., Mettler, F. A., Wagner, L. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Skin+injuries+from+fluoroscopically+guided+procedures:+part+1,+characteristics+of+radiation+injury.">Skin injuries from fluoroscopically guided procedures: part 1, characteristics of radiation injury.</a> AJR Am. J. Roentgenol. 177, 3-11 (2001).</li><li>Koenig, T. R., Mettler, F. A., Wagner, L. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Skin+injuries+from+fluoroscopically+guided+procedures:+part+2,+review+of+73+cases+and+recommendations+for+minimizing+dose+delivered+to+patient.">Skin injuries from fluoroscopically guided procedures: part 2, review of 73 cases and recommendations for minimizing dose delivered to patient.</a> AJR Am. J. Roentgenol. 177, 13-20 (2001).</li><li>Arenson, R. L. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetically+directable+remote+guidance+systems,+and+methods+and+use+thereof.">Magnetically directable remote guidance systems, and methods and use thereof.</a> United States Patent. , (2001).</li><li>Roberts, T. P., Hassenzahl, W. V., Hetts, S. W., Arenson, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remote+control+of+catheter+tip+deflection:+an+opportunity+for+interventional+MRI.">Remote control of catheter tip deflection: an opportunity for interventional MRI.</a> Magn. Reson. Med. 48, 1091-1095 (2002).</li><li>Malba, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laser-lathe+lithography+-+a+novel+method+for+manufacturing+nuclear+magnetic+resonance+microcoils.">Laser-lathe lithography - a novel method for manufacturing nuclear magnetic resonance microcoils.</a> Biomed. Microdevices. 5, 21-27 (2003).</li><li>Bernhardt, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Steerable+catheter+microcoils+for+interventional+MRI+reducing+resistive+heating.">Steerable catheter microcoils for interventional MRI reducing resistive heating.</a> Academic radiology. 18, 270-276 (2011).</li><li>Muller, L., Saeed, M., Wilson, M. W., Hetts, S. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remote+control+catheter+navigation:+options+for+guidance+under+MRI.">Remote control catheter navigation: options for guidance under MRI.</a> Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 14, 33 (2012).</li><li>Wilson, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+catheter+manipulation+in+the+interventional+MRI+environment.">Magnetic catheter manipulation in the interventional MRI environment.</a> J. Vasc. Interv. Radiol. , (2013).</li></ol>

Dr. Hetts erhielt gewähren Unterstützung von Stryker Corporation und ist ein bezahlter Berater für Silk Road Medical, Inc.

Hier beschreiben wir die Protokoll für Ablenkung eines Mikrokatheters in einem MR-Scanners. Die wesentlichen Parameter für den Erfolg sind genaue Anwendung der aktuellen und Messung der Ablenkwinkel. Ungenaue Messung der Ablenkwinkel ist die wahrscheinlichste Fehler in diesem Protokoll angetroffen. Die Winkel in MR-Bildern während des Experiments Wasserbad eingefangen ggf. Werte durch geringe Unterschiede in der Orientierung durch die das Medium in Bezug auf die Bohrung des Magneten angeordnet ist, unterscheiden. Um ...

Endovaskuläre Eingriffe in der interventionellen Medizin Verwendung x-ray Führung als Werkzeug für Katheter Navigation durch das Gefäßsystem zu mehreren wichtigen Krankheiten wie Gehirn-Aneurysma, ischämischer Schlaganfall, soliden Tumoren, Arteriosklerose und Herzrhythmusstörungen Targeting über eine Million Patienten pro Jahr weltweit 1 Behandlung durchgeführt - 5. Mit der Verwendung von Kontrastmitteln, wird die Navigation durch das Gefäßsystem durch manuelle Drehung des Katheters und durch den mechanischen Vorschub interventionistischen Hand 6 gelöst. Jedoch wird die Navigation durch kleine gewundene Blutgefäße um viele Biegungen vaskulären zunehmend schwierig, Verlängern der Zeit vor Erreichen des Zielortes. Dies stellt ein Problem für zeitkritische Verfahren wie die Entfernung eines Gerinnsels in einer verstopften Blutgefäßes. Zusätzlich erhöhen das Verfahren verlängert die Strahlendosis und schaffen das Potenzial für Nebenwirkungen 7-11. Allerdings endovaskuläre Eingriffe unter Magneti durchgeführtc-Resonanz-Tomographie kann eine Lösung bieten. Die starke homogenes Magnetfeld eines MRI-Scanners kann Katheterspitze Navigation durch Fernsteuerung 12,13 ausnutzen. Strom, der an einer Mikrowendel bei einer Katheterspitze befindet induziert eine kleine magnetische Moment, das ein Drehmoment erfährt, wie es mit der Bohrung des MRI Scanner 13 (Figur 1) ausgerichtet ist. Wenn elektrischer Strom in einer einzelnen Spule aktiviert ist, kann die Katheterspitze in einer Ebene durch Fernsteuerung abgelenkt werden. Wenn drei Spulen bei einer Katheterspitze erregt sind, können Katheterspitze Auslenkung in drei Dimensionen erreicht werden. Somit weist magnetisch erleichtert Lenken eines Katheters des Potentials, um die Geschwindigkeit und Wirksamkeit der vaskulären Navigation in endovaskuläre Verfahren, die Prozedur zu verkürzen könnte Patienten zu verbessern und zu erhöhen. In dieser Studie untersuchten wir, ob Strom, der an einer Mikrowendel-bestückte endovaskulären Katheter zuverlässig und kontrolliert deflecti produzieren kannons unter MR-Leitlinien Vorprüfung des Katheters Navigation Studien.

<table border="1">
<tbody>
 <tr>
 <td>Name of Reagent/Material</td>
 <td>Company</td>
 <td>Catalog Number</td>
 <td>Comments</td>
 </tr>
 <tr>
 <td>GdDTPA Contrast Media (Magnevist)</td>
 <td>Bayer HealthCare Pharmaceuticals Inc. </td>
 <td>1240340</td>
 <td>McKesson Material Number</td>
 </tr>
 <tr>
 <td>Positive Photoresist</td>
 <td>Shipley</td>
 <td>N/A</td>
 <td>PEPR-2400, Replacement: Dow Chemicals Intervia 3D-P </td>
 </tr>
 <tr>
 <td>Copper Sulfate</td>
 <td>ScienceLab</td>
 <td>SLC3778</td>
 <td>Crystal form</td>
 </tr>
 <tr>
 <td>Sulfuric Acid</td>
 <td>ScienceLab</td>
 <td>SLS1573</td>
 <td>50% w/w solution</td>
 </tr>
 <tr>
 <td>Parrafin Wax</td>
 <td>Carolina</td>
 <td>879190</td>
 <td></td>
 </tr>
 <tr>
 <td>Potassium Carbonate </td>
 <td>Acros Organics</td>
 <td>424081000</td>
 <td></td>
 </tr>
</tbody>
 </table>

magnetically-assisted remote controlled microcatheter tip deflection under magnetic resonance imaging

Röntgendurchleuchtung-geführte endovaskuläre Verfahren haben mehrere erhebliche Beschränkungen, auch schwierige Katheter Navigation und Verwendung von ionisierender Strahlung, die möglicherweise überwunden werden können mit einem magnetisch steuerbaren Katheter unter MR-Steuerung werden. Das Hauptziel dieser Arbeit ist es, einen Mikrokatheter deren Spitze ferngesteuert werden mit dem Magnetfeld des MR-Scanner zu entwickeln. Dieses Protokoll zielt darauf ab, die Verfahren für die Bestromung der Mikrospule Spitze Mikrokatheter, um konsistente und kontrollierbare Ausschläge erzeugen beschreiben. Ein Mikrospule wurde hergestellt unter Verwendung eines Lasers auf eine Drehmaschine Lithographie Polyimid-bestückte endovaskulären Katheters. In vitro Testung wurde in einem Wasserbad und Gefäß Phantom unter Anleitung eines 1,5-T MR-System mit stationären freier Präzession (SSFP) Sequenzierung durchgeführt. Verschiedene Strommengen wurden den Spulen des Mikrokatheters angewendet mea produzierensureable Spitze Umlenkungen und navigieren Sie in der vaskulären Phantome. Die Entwicklung dieses Gerätes bietet eine Plattform für zukünftige Tests und Gelegenheit zu endovaskulären interventionellen MRI-Umgebung zu revolutionieren.

Aus dem oben beschriebenen Protokoll, eine Abwinkelung zwischen 0 und 90 Grad aus der Anwendung sollte von 50-300 mA Strom gleichzeitig auf beide Spulen eines kombinierten Elektromagnet und Helmholtzspule Mikrokatheter System (2E) geliefert beobachtet werden. Eine Erhöhung der angelegten Strom sollte zu einem Anstieg der Mikrokatheter Ablenkwinkel führen, während eine Umkehr der Strompolarität sollte Auslenkung in entgegengesetzte Richtung führt, wie mit positiven Strom beobachtet (5A-5C).<...

Watch this Scientific Journal Video about Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging at JoVE.com

Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

Strom, der an einer endovaskulären Mikrokatheter mit Mikrospule Spitze durch Laserschweißen Drehmaschine Lithographie hergestellt werden steuerbaren Verformungen unter Magnetresonanz (MR)-Führung, die Geschwindigkeit und Wirksamkeit der Navigation des Gefäßsystem während verschiedener endovaskulären Verfahren kann verbessert erreichen.

Magnetisch-Assisted Remote Controlled Microcatheter Tip Durchbiegung unter Magnetic Resonance Imaging

X-ray fluoroscopy-guided  endovascular procedures have several significant limitations, including  difficult catheter navigation and use of ionizing ...

magnetically-assisted-remote-controlled-microcatheter-tip-deflection

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12.3K Aufrufe.  University of California, San Francisco. Strom, der an einer endovaskulären Mikrokatheter mit Mikrospule Spitze durch Laserschweißen Drehmaschine Lithographie hergestellt werden steuerbaren Verformungen unter Magnetresonanz (MR)-Führung, die Geschwindigkeit und Wirksamkeit der Navigation des Gefäßsystem während verschiedener endovaskulären Verfahren kann verbessert erreichen.

Serie: Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use of destructive assessment is not acceptable. A proposed alternative is the use of an imaging process called magnetic resonance elastography. Elastography is a nondestructive method for determining the engineered outcome by measuring local mechanical property values (i.e., complex shear modulus), which are essential markers for identifying the structure and functionality of a tissue. As a noninvasive means for evaluation, the monitoring of engineered constructs with imaging modalities such as magnetic resonance imaging (MRI) has seen increasing interest in the past decade1. For example, the magnetic resonance (MR) techniques of diffusion and relaxometry have been able to characterize the changes in chemical and physical properties during engineered tissue development2. The method proposed in the following protocol uses microscopic magnetic resonance elastography (&mu;MRE) as a noninvasive MR based technique for measuring the mechanical properties of small soft tissues3. MRE is achieved by coupling a sonic mechanical actuator with the tissue of interest and recording the shear wave propagation with an MR scanner4. Recently, &mu;MRE has been applied in tissue engineering to acquire essential growth information that is traditionally measured using destructive mechanical macroscopic techniques5. In the following procedure, elastography is achieved through the imaging of engineered constructs with a modified Hahn spin-echo sequence coupled with a mechanical actuator. As shown in Figure 1, the modified sequence synchronizes image acquisition with the transmission of external shear waves; subsequently, the motion is sensitized through the use of oscillating bipolar pairs. Following collection of images with positive and negative motion sensitization, complex division of the data produce a shear wave image. Then, the image is assessed using an inversion algorithm to generate a shear stiffness map6. The resulting measurements at each voxel have been shown to strongly correlate (R2&gt;0.9914) with data collected using dynamic mechanical analysis7. In this study, elastography is integrated into the tissue development process for monitoring human mesenchymal stem cell (hMSC) differentiation into adipogenic and osteogenic constructs as shown in Figure 2.

The procedure demonstrates the methodology of magnetic resonance elastography for monitoring the engineered outcome of adipose and osteogenic tissue engineered constructs through noninvasive local assessment of the mechanical properties using microscopic magnetic resonance elastography (&mu;MRE).

Magnet-Resonanz-Elastographie Methodik für die Beurteilung von Tissue Engineering gewonnenen Konstrukts Wachstum

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use ...

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Biotechnik

Remote Magnetic Actuation of Micrometric Probes for in situ 3D Mapping of Bacterial Biofilm Physical Properties

Bacterial adhesion and growth on interfaces lead to the formation of three-dimensional heterogeneous structures so-called biofilms. The cells dwelling in these structures are held together by physical interactions mediated by a network of extracellular polymeric substances. Bacterial biofilms impact many human activities and the understanding of their properties is crucial for a better control of their development &#8212; maintenance or eradication &#8212; depending on their adverse or beneficial outcome. This paper describes a novel methodology aiming to measure in situ the local physical properties of the biofilm that had been, until now, examined only from a macroscopic and homogeneous material perspective. The experiment described here&#160;involves introducing magnetic particles into a growing biofilm to seed local probes that can be remotely actuated without disturbing the structural properties of the biofilm. Dedicated magnetic tweezers were developed to exert a defined force on each particle embedded in the biofilm. The setup is mounted on the stage of a microscope to enable the&#160;recording of time-lapse images of the particle-pulling period. The particle trajectories are then extracted from the pulling sequence and the local viscoelastic parameters are derived from each particle displacement curve, thereby providing the 3D-spatial distribution of the parameters. Gaining insights into the biofilm mechanical profile is essential from an engineer&#39;s point of view for biofilm control purposes but also from a fundamental perspective to clarify the relationship between the architectural properties and the specific biology of these structures.

Remote Magnetic Actuation of Micrometric Probes for in situ 3D Mapping of Bacterial Biofilm Physical Properties

This paper shows an original methodology based on the remote actuation of magnetic particles seeded in a bacterial biofilm and the development of dedicated magnetic tweezers to measure in situ the local mechanical properties of the complex living material built by micro-organisms at interfaces.

Fern Magnetische Betätigung des Mikrometrische Sonden für<em&gt; In situ</em&gt; 3D-Mapping der bakteriellen Biofilm Physikalische Eigenschaften

Bacterial adhesion and growth on interfaces lead to the formation of three-dimensional heterogeneous structures so-called biofilms. The cells dwelling in ...

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e.,&#160;gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

AN MRI-compatible&#160;custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

Kundenspezifische Laser-basierte Heizvorrichtung zum ausgelöste Freisetzung von Cisplatin von wärmeempfindlichen Liposomen mit Magnet-Resonanz-Bild Anleitung

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of smart soft devices for biomedical applications. Although a number of magnetically-responsive drug delivery systems have demonstrated efficacies through either in vitro proof of concept studies or in vivo preclinical applications, their use in clinical settings is still limited by their insufficient biocompatibility or biodegradability. Additionally, many of the existing platforms rely on sophisticated techniques for their fabrications. We recently demonstrated the fabrication of biodegradable, gelatin-based thermo-responsive microgel by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within a three-dimensional gelatin network. In this study, we present a facile method to fabricate a biodegradable drug release platform that enables a magneto-thermally triggered drug release. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and thermo-responsive polymers within gelatin-based colloidal microgels, in conjunction with an alternating magnetic field application system.

We present a facile method to fabricate a biodegradable gelatin-based drug release platform that is magneto-thermally responsive. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and poly(N-isopropylacrylamide-co-acrylamide) within a spherical gelatin micro-network crosslinked by genipin, in conjunction with an alternating magnetic field application system.

Magnetisches Wechselfeld-Responsive Hybrid Gelatine Mikrogele der gezielten Medikamentenapplikation

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of ...

Rapid Scan Electron Paramagnetic Resonance Opens New Avenues for Imaging Physiologically Important Parameters In Vivo

We demonstrate a superior method of 2D spectral-spatial imaging of stable radical reporter molecules at 250 MHz using rapid-scan electron-paramagnetic-resonance (RS-EPR), which can provide quantitative information under in vivo conditions on oxygen concentration, pH, redox status and concentration of signaling molecules (i.e., OH&#8226;, NO&#8226;). The RS-EPR technique has a higher sensitivity, improved spatial resolution (1 mm), and shorter acquisition time in comparison to the standard continuous wave (CW) technique. A variety of phantom configurations have been tested, with spatial resolution varying from 1 to 6 mm, and spectral width of the reporter molecules ranging from 16 &#181;T (160 mG) to 5 mT (50 G). A cross-loop bimodal resonator decouples excitation and detection, reducing the noise, while the rapid scan effect allows more power to be input to the spin system before saturation, increasing the EPR signal. This leads to a substantially higher signal-to-noise ratio than in conventional CW EPR experiments.

Rapid Scan Electron Paramagnetic Resonance Opens New Avenues for Imaging Physiologically Important Parameters In Vivo

A new electron paramagnetic resonance (EPR) method, rapid scan EPR (RS-EPR), is demonstrated for 2D spectral spatial imaging which is superior to the traditional continuous wave (CW) technique and opens new venues for in vivo imaging. Results are demonstrated at 250 MHz, but the technique is applicable at any frequency.

Rapid-Scan-Elektronenspinresonanz eröffnet neue Wege für Imaging Physiologisch Wichtige Parameter<em&gt; In Vivo</em

We demonstrate a superior method of 2D spectral-spatial imaging of stable radical reporter molecules at 250 MHz using rapid-scan ...

Magnetic Levitation Coupled with Portable Imaging and Analysis for Disease Diagnostics

Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for specialized equipment and trained personnel require that many diagnostic tests be performed at remote, centralized clinical laboratories. Magnetic levitation is a simple yet powerful technique and can be applied to levitate cells, which are suspended in a paramagnetic solution and placed in a magnetic field, at a position determined by equilibrium between a magnetic force and a buoyancy force. Here, we present a versatile platform technology designed for point-of-care diagnostics which uses magnetic levitation coupled to microscopic imaging and automated analysis to determine the density distribution of a patient's cells as a useful diagnostic indicator. We present two platforms operating on this principle: (i) a smartphone-compatible version of the technology, where the built-in smartphone camera is used to image cells in the magnetic field and a smartphone application processes the images and to measures the density distribution of the cells and (ii) a self-contained version where a camera board is used to capture images and an embedded processing unit with attached thin-film-transistor (TFT) screen measures and displays the results. Demonstrated applications include: (i) measuring the altered distribution of a cell population with a disease phenotype compared to a healthy phenotype, which is applied to sickle cell disease diagnosis, and (ii) separation of different cell types based on their characteristic densities, which is applied to separate white blood cells from red blood cells for white blood cell cytometry. These applications, as well as future extensions of the essential density-based measurements enabled by this portable, user-friendly platform technology, will significantly enhance disease diagnostic capabilities at the point of care.

We present a magnetic levitation technique coupled with automated imaging and analysis in both a smartphone-compatible device and a device with embedded imaging and processing. This is applied to measure the density distribution of cells with two demonstrated biomedical applications: sickle cell disease diagnosis and separating white and red blood cells.

Magnetic Levitation Gekoppelt mit tragbaren Imaging und Analyse für Krankheitsdiagnostik

Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for ...

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant &#34;burst release&#34; of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe3O4-NH2 nanoparticles for the potential use in magnetically and thermally triggered drug-release.

Magnetisches und thermisch empfindliches Poly (<em&gt; N.</em&gt; -isopropylacrylamid) -basierte Mikrogele für die magnetisch getriggerte kontrollierte Freisetzung

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

Metabolic Support of Excised, Living Brain Tissues During Magnetic Resonance Microscopy Acquisition

This protocol describes the procedures necessary to support normal metabolic functions of acute brain slice preparations during the collection of magnetic resonance (MR) microscopy data. While it is possible to perform MR collections on living, excised mammalian tissue, such experiments have traditionally been constrained by resolution limits and are thus incapable of visualizing tissue microstructure. Conversely, MR protocols that did achieve microscopic image resolution required the use of fixed samples to accommodate the need for static, unchanging conditions over lengthy scan times. The current protocol describes the first available MR technique that enables imaging of living, mammalian tissue samples at microscopic resolutions. Such data is of great importance to the understanding of how pathology-based contrast changes occurring at the microscopic level influence the content of macroscopic MR scans such as those used in the clinic. Once such an understanding is realized, diagnostic methods with greater sensitivity and accuracy can be developed, which will translate directly to earlier disease treatment, more accurate therapy monitoring and improved patient outcomes.
While the described methodology focuses on brain slice preparations, the protocol is adaptable to any excised tissue slice given that changes are made to the gas and perfusate preparations to accommodate the tissue&#39;s specific metabolic needs. Successful execution of the protocol should result in living, acute slice preparations that exhibit MR diffusion signal stability for periods up to 15.5 h. The primary advantages of the current system over other MR compatible perfusion apparatuses are its compatibility with the MR microscopy hardware required to attain higher resolution images and ability to provide constant, uninterrupted flow with carefully regulated perfusate conditions. Reduced sample throughput is a consideration with this design as only one tissue slice may be imaged at a time.

The current protocol describes a method by which users can maintain viability of acute hippocampal and cortical slice preparations during the collection of magnetic resonance microscopy data.

Metabolische Unterstützung der herausgeschnitten, lebendes Gehirn Gewebe während der Magnet-Resonanz-Mikroskopie-Akquisition

This protocol describes the procedures necessary to support normal metabolic functions of acute brain slice preparations during the collection of magnetic ...

Measuring the Spin-Lattice Relaxation Magnetic Field Dependence of Hyperpolarized [1-13C]pyruvate

The fundamental limit to in vivo imaging applications of hyperpolarized 13C-enriched compounds is their finite spin-lattice relaxation times. Various factors affect the relaxation rates, such as buffer composition, solution pH, temperature, and magnetic field. In this last regard, the spin-lattice relaxation time can be measured at clinical field strengths, but at lower fields, where these compounds are dispensed from the polarizer and transported to the MRI, the relaxation is even faster and difficult to measure. To have a better understanding of the amount of magnetization lost during transport, we used fast field-cycling relaxometry, with magnetic resonance detection of 13C nuclei at ~0.75 T, to measure the nuclear magnetic resonance dispersion of the spin-lattice relaxation time of hyperpolarized [1-13C]pyruvate. Dissolution dynamic nuclear polarization was used to produce hyperpolarized samples of pyruvate at a concentration of 80 mmol/L and physiological pH (~7.8). These solutions were rapidly transferred to a fast field-cycling relaxometer so that relaxation of the sample magnetization could be measured as a function of time using a calibrated small flip angle (3&#176;-5&#176;). To map the T1 dispersion of the C-1 of pyruvate, we recorded data for different relaxation fields ranging between 0.237 mT and 0.705 T. With this information, we determined an empirical equation to estimate the spin-lattice relaxation of the hyperpolarized substrate within the mentioned range of magnetic fields. These results can be used to predict the amount of magnetization lost during transport and to improve experimental designs to minimize signal loss.

Measuring the Spin-Lattice Relaxation Magnetic Field Dependence of Hyperpolarized [1-13C]pyruvate

We present a protocol to measure the magnetic field dependence of the spin-lattice relaxation time of 13C-enriched compounds, hyperpolarized by means of dynamic nuclear polarization, using fast field-cycled relaxometry. Specifically, we have demonstrated this with [1-13C]pyruvate, but the protocol could be extended to other hyperpolarized substrates.

Messung der Spin-Lattice Relaxation Magnetfeldabhängigkeit von hyperpolarisiertem [1-13C]pyruvat

The fundamental limit to in vivo imaging applications of hyperpolarized 13C-enriched compounds is their finite spin-lattice relaxation times. Various ...

High-resolution Imaging of Nuclear Dynamics in Live Cells under Uniaxial Tensile Strain

Extracellular mechanical strain is known to elicit cell phenotypic responses and has physiological relevance in several tissue systems. To capture the effect of applied extracellular tensile strain on cell populations in vitro via biochemical assays, a device has previously been designed which can be fabricated simply and is small enough to fit inside tissue culture incubators, as well as on top of microscope stages. However, the previous design of the polydimethylsiloxane substratum did not allow high-resolution subcellular imaging via oil-immersion objectives. This work describes a redesigned geometry of the polydimethylsiloxane substratum and a customized imaging setup that together can facilitate high-resolution subcellular imaging of live cells while under applied strain. This substratum can be used with the same, earlier designed device and, hence, has the same advantages as listed above, in addition to allowing high-resolution optical imaging. The design of the polydimethylsiloxane substratum can be improved by incorporating a grid which will facilitate tracking the same cell before and after the application of strain. Representative results demonstrate high-resolution time-lapse imaging of fluorescently labeled nuclei within strained cells captured using the method described here. These nuclear dynamics data give insights into the mechanism by which applied tensile strain promotes differentiation of oligodendrocyte progenitor cells.&#160;

Using a previously designed device to apply mechanical strain to adherent cells, this paper describes a redesigned substratum geometry and a customized apparatus for high-resolution single-cell imaging of strained cells with a 100x oil immersion objective.

Hochauflösende Bildgebung von Kerndynamik in Live-Zellen unter Uniaxialer Tensile-Straße

Extracellular mechanical strain is known to elicit cell phenotypic responses and has physiological relevance in several tissue systems. To capture the ...