Pallav Kolli, Settecase Fabio, Amans Mateo, y Robert Taylor de UCSF, Tim Roberts de la Universidad de Pennsylvania Fuentes de Financiamiento NIH Instituto Nacional del Corazón Pulmón Blood Institute (NHLBI) Premio (M. Wilson): 1R01HL076486 Sociedad Americana de Neurorradiología de Investigación y Educación de la Fundación Premio Académico (S. Hetts) NIH Instituto Nacional de Imágenes Biomédicas y Bioingeniería (NIBIB) Premio (S. Hetts): 1R01EB012031

1. Microespiral Fabrication <ol><li> Obtener un microcatéter disponible comercialmente (por ejemplo 2.3F tránsito rápido Cordis catéter neurovascular, de Raynham, MA) para un sustrato. </li><li> Asegúrese de catéteres no tienen componentes ferrosos, se consideran MR-safe, y varían en tamaño 2.3-3.0 F. </li><li> Catódica una capa de adhesión de titanio seguida de una capa de siembra de cobre hasta un 1 a 2 mm OD tubo aislante. Los posibles materiales incluyen poliimida o alúmina (ORtech Advanced Ceramics, Sacramento, CA). </li><li> Electrodepositar una capa fotorresistente positiva utilizando Shipley PEPR-2400 (actualmente comercializado por Dow Chemical bajo el nombre Intervia 3D-P). Resultados de electrodeposición en un revestimiento uniforme sobre la superficie cilíndrica no plana. </li><li> Fotorresistente se expone por un láser único sistema de escritura directa (láser torno, un sistema no comercial desarrollado en el Lawrence Livermore National Laboratory) en el patrón de la forma de la bobina deseada (Figura 2A). Esta es una modificaciónción de la técnica originalmente descrita en Malba et al. 14 </li><li> Desarrollar el fotoprotector expuesto en una solución al 1% de carbonato de potasio a 35 ° C. </li><li> El cobre se electrochapado a través de la máscara de resistencia restante para formar la bobina deseada. El sistema puede fabricar tanto solenoide y de Helmholtz (racetrack) patrones de cobre (Figuras 2C y 2D). </li><li> Después de la electrodeposición de cobre, retire la capa protectora con el desarrollador caliente. Eliminar la capa de siembra de cobre, seguido por la capa de adhesión de titanio. </li><li> Una el tubo aislante a la punta del catéter utilizando envoltura retráctil para completar el montaje. Asegúrese de que el envoltorio cubre la punta en espiral completa. Para el montaje de ejes múltiples catéteres colocar aislantes estructuras de tubos uno dentro del otro como se muestra en la Figura 2E. </li><li> Haga pasar los cables de cobre a través del lumen del microcatéter y soldadura a las bobinas en la punta. </li><li> Modificar y acortar a 6 pies de cable RJ11 de teléfono to 3 pies de largo. </li><li> Conectar los cables de cobre que emanan del buje extremo posterior del microcatéter a la línea telefónica modificada 3 ft gato de transmisión. </li></ol> 2. Baño de agua de instalación <ol><li> Hacer un pequeño agujero en el centro del lado de un recipiente de plástico de aproximadamente 5 cm de la parte inferior. </li><li> Inserte una vaina 9F Avanti Cordis vascular (Cordis Endovascular, Miami Lakes, FL) a través del agujero. </li><li> Cortar la punta distal de la vaina vascular dejando un 4 cm de largo pieza que se extiende en la cuenca. </li><li> En el extremo de la funda, adjuntar una válvula rotativa hemostático o Thuoy Borst-para estabilizar la posición del microcatéter. </li><li> Llene el recipiente con agua destilada asegurar la inmersión completa del aparato. </li><li> Inserte el catéter con punta en espiral a través de la vaina vascular y la válvula. </li><li> Mida y registre la longitud ilimitada del microcatéter se extiende desde la válvula en el tanque de agua. </li><li> Coloque el tanque de agua con microsistema de catéter dentro del imán del escáner de RM y orientar con respecto al taladro del imán. </li><li> Conecte el cable de teléfono modificado 3 pies al catéter a un 25 pies RJ11 línea telefónica de transmisión de cable con un conector de teléfono de 2 vías. </li><li> Conecte el otro extremo del cable de 25 pies de teléfono a un Lambda LPD-422A-FM doble fuente de alimentación regulada para entregar hasta 1 A de corriente al dispositivo. </li><li> Colocar las líneas de transmisión a través de una guía de ondas y la fuente de alimentación fuera de la sala de escáner de RM fuera de la línea de 5 Gauss. </li></ol> 3. Buque Fantasma de configuración <ol><li> Construir un fantasma recipiente hueco con una intersección en forma de Y a partir de tubo de goma antes de la experimentación. </li><li> Llenar el recipiente fantasma con una solución 0,0102 M de gadopentetato de dimeglumina (GdDTPA) (Magnevist, Bayer Healthcare Pharmaceuticals, Montville, Nueva Jersey) en agua destilada para crear un contraste entre los vasos fantasma y el fondo. </li><li> Montar el microcatheter sistema como se describe en los pasos a través de 1,1 1,9. Conectar el catéter a la fuente de alimentación y la posición como se describe en los pasos 2,9 a 2,11. </li><li> Colocar la punta del microcatéter en la base de la abertura del recipiente. </li><li> Coloque el fantasma dentro del imán del escáner de RM y orientar con respecto al taladro del imán. </li></ol> 4. Imágenes por Resonancia Magnética <ol><li> Realizar imágenes con un sistema 1.5T MR clínico (Siemens Avanto, SW: Syngo B13, Erlangen, Alemania; Philips Achieva, SW versión 2.1, Cleveland, OH). </li><li> Aplicar &lt;50 mA de corriente para visualizar la posición de la punta del catéter. Bajo MRI, un momento magnético pequeño será producido en la punta del catéter para visualizar un artefacto distinto de forma variable en función de que las bobinas se energizan. </li><li> Aplique una cantidad variable de corriente en el rango de ± 100 mA de la fuente de poder dual Lambda a las bobinas de desviación de la punta y observar (Figuras 3A-3C) en el ba aguaª de configuración. Debido desviación de la punta es casi instantánea, actual necesita solamente ser aplicado para ~ 1-2 segundos para visualizar la deflexión máxima. </li><li> Repetir y grabar aplicaciones consecutivas de cantidades fijas de corriente. </li><li> Repetir el paso 4,2, mientras que simultáneamente empuja el catéter a mano permitiendo avance mecánico a través del vaso fantasma (Figuras 4A y 4B). Aplicar corriente en el punto de ramificación para desviar la punta del catéter en el vaso deseado. Avanzar el catéter en la bifurcación del vaso empujando manualmente el extremo del catéter (Figura 4C). Retraer el catéter a la bifurcación recipiente y repetir en la rama opuesta (Figura 4D). </li><li> Adquirir imágenes de RM utilizando una instantánea 2D-FLASH secuencia (TR = 30 ms, TE = 1,4 mseg, una matriz de 256 x128 y ángulo de giro ~ 30 °). </li></ol> 5. Las mediciones de deflexión Analizar y medir las deflexiones angulares de las imágenes capturadas duranteexperimentos baño de agua con diferentes aplicaciones informáticas (cualquier Imagen Digital y Comunicaciones en Medicina (DICOM) Visor).

<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 recibió subsidios de Stryker Corporation y es un consultor pagado para Silk Road Medical, Inc.

Aquí se describe el protocolo para la deflexión de un microcatéter en un escáner de RM. Los parámetros clave para el éxito son una aplicación precisa de la corriente y de medición de ángulo de desviación. Medición inexacta del ángulo de desviación es el error más probable encontrar en este protocolo. Los ángulos capturados en las imágenes de RM durante el experimento baño de agua pueden diferir de los valores reales debido a ligeras diferencias en la orientación mediante el cual se coloca el medio con ...

Los procedimientos endovasculares realizados en el uso de la medicina intervencionista guía de rayos X como una herramienta para la navegación a través de catéter vascular para el tratamiento de varias enfermedades graves, como el aneurisma cerebral, infarto cerebral, tumores sólidos, la aterosclerosis y las arritmias cardíacas dirigida a más de un millón de pacientes al año en todo el mundo 1 - 5. Con el uso de medios de contraste, la navegación a través de la vasculatura se logra mediante el giro manual del catéter y el avance mecánico por el intervencionista de mano 6. Sin embargo, la navegación a través de pequeños vasos sanguíneos tortuosos alrededor de muchas curvas vasculares se vuelve cada vez más difícil, alargando el tiempo antes de alcanzar el sitio diana. Esto plantea un problema para los procedimientos sensibles al tiempo tales como la remoción de un coágulo en un vaso sanguíneo ocluido. Además, los procedimientos prolongados aumentar la dosis de radiación y crear el potencial de eventos adversos 7-11. Sin embargo, los procedimientos endovasculares realiza bajo Magnetic resonancia puede ser una solución. El fuerte campo magnético homogéneo de un escáner de MRI pueden ser explotados para la navegación punta de catéter por control remoto 12,13. La corriente aplicada a una microespira encuentra en una punta de catéter induce un pequeño momento magnético, que experimenta una torsión, ya que se alinea con el orificio del escáner de MRI 13 (Figura 1). Si la corriente eléctrica se activa en una bobina individual, la punta del catéter puede ser desviada en un plano por control remoto. Si tres bobinas en la punta del catéter se energizan, desviación punta del catéter se puede lograr en tres dimensiones. Así, dirección magnéticamente facilitado de un catéter tiene el potencial de aumentar la velocidad y la eficacia de la navegación vascular en los procedimientos endovasculares, lo que podría reducir los tiempos del procedimiento y mejorar los resultados del paciente. En este estudio, hemos examinado si la corriente aplicada a un catéter endovascular microespiral de punta puede producir fiable y controlado deflections bajo MR-guía como las pruebas preliminares de los estudios de localización de catéteres.

<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

Procedimientos de fluoroscopia de rayos X guiada endovasculares tienen varias limitaciones significativas, incluyendo la navegación del catéter difícil y el uso de radiación ionizante, que potencialmente pueden ser superados usando un catéter magnéticamente orientable bajo la guía MR. El objetivo principal de este trabajo es desarrollar un micro-catéter cuya punta puede ser controlado remotamente usando el campo magnético del escáner de RM. Este protocolo tiene como objetivo describir los procedimientos de aplicación actual para el microcatéter microespiral de punta para producir desviaciones consistentes y controlables. Un microespira se fabricó usando litografía láser torno a un catéter endovascular poliimida de punta. En las pruebas in vitro se realizó en un baño de agua y fantasma buque bajo la guía de un sistema de 1,5-T MR utilizando el estado de equilibrio precesión libre (SSFP) secuenciación. Varias cantidades de corriente se aplica a las bobinas del microcatéter para producir meadeflexiones sureable punta y navegar en fantasmas vasculares. El desarrollo de este dispositivo proporciona una plataforma para futuras pruebas y la oportunidad de revolucionar el ambiente RM intervencionista endovascular.

Desde el protocolo descrito anteriormente, un ángulo de deflexión entre 0 y 90 grados debe observar desde la aplicación de 50-300 mA de corriente suministrada simultáneamente a ambas bobinas de un solenoide combinado y bobina de Helmholtz sistema de microcatéter (2E Figura). Un aumento de la corriente aplicada se traducirá en un aumento en el ángulo de deflexión microcatéter, mientras que un cambio en la polaridad de la corriente debe dar lugar a la flexión en la dirección opuesta como se obs...

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

La corriente aplicada a un microcatéter endovascular con punta microespiral hecha por láser litografía torno puede lograr deflexiones bajo controlables por resonancia magnética (MR) de orientación, que puede mejorar la velocidad y eficacia de la navegación de la vasculatura durante diversos procedimientos endovasculares.

Magnéticamente Asistencia Remota Controlada microcatéter desviación de la punta bajo la resonancia magnética

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

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12.3K vistas.  University of California, San Francisco. La corriente aplicada a un microcatéter endovascular con punta microespiral hecha por láser litografía torno puede lograr deflexiones bajo controlables por resonancia magnética (MR) de orientación, que puede mejorar la velocidad y eficacia de la navegación de la vasculatura durante diversos procedimientos endovasculares.

Video: 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).

Metodología elastografía por resonancia magnética para la Evaluación de los tejidos Diseñado crecimiento Construct

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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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.

El accionamiento a distancia magnética del micrométrica Sondas para<em&gt; In situ</em&gt; Mapping 3D bacterianas Biofilm Propiedades Físicas

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.

Diseño personalizado basado en láser máquinas de calentamiento para lanzamiento disparada de cisplatino de termosensible liposomas con Resonancia Magnética Orientación Imagen

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.

Alternando microgeles de gelatina de campo híbrido-Responsive magnéticos para 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 ...

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.

El rápido escaneo de electrones resonancia paramagnética abre nuevas vías para Imaging fisiológicamente parámetros importantes<em&gt; En 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.

Levitación magnética Junto con Imaging portátil y Análisis para el diagnóstico de enfermedades

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.

Poliuretano Magnético y Térmico<emN</em&gt; -isopropilacrilamida) para liberación controlada magnéticamente

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.

Apoyo metabólico de suprimidos, los tejidos de cerebro vivos durante la adquisición de la microscopía de resonancia magnética

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.

Medición de la dependencia del campo magnético de relajación Spin-Lattice de hiperpolarizado [1-13C]pyruvate

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.

Imágenes de alta resolución de la dinámica nuclear en células vivas bajo tensión de tracción uniaxial

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