Pallav Kolli, Fabio Settecase, Matthew Amans, et Robert Taylor, de l&#39;UCSF, Tim Roberts, de l&#39;Université de Pennsylvanie Sources de financement National Heart Lung NIH Blood Institute (NHLBI) Prix (M. Wilson): 1R01HL076486 American Society of Neuroradiology recherche et l&#39;éducation Scholar Award (S. Hetts) NIH Institut national d&#39;imagerie biomédicale et bio-ingénierie (NIBIB) Prix (S. Hetts): 1R01EB012031

1. Fabrication microbobine <ol><li> Procurez-vous un microcathéter disponible dans le commerce (par exemple 2.3f Rapid Transit Cordis neurovasculaire cathéter, Raynham, MA) pour un substrat. </li><li> Assurez-cathéters n&#39;ont pas de composants ferreux, sont considérés comme MR-fort, et vont de 2,3 à 3,0 F. </li><li> Pulvérisation d&#39;une couche d&#39;adhésion de titane suivie d&#39;une couche de germination de cuivre à l&#39;état d&#39;1 à 2 mm diamètre extérieur du tube isolant. Matériaux possibles comprennent polyimide ou d&#39;alumine (Ortech Advanced Ceramics, Sacramento, CA). </li><li> Dépôt électrolytique d&#39;une couche de résine photosensible positive en utilisant Shipley PEPR-2400 (actuellement vendu par Dow Chemical sous le nom Intervia 3D-P). Les résultats d&#39;électrodéposition dans un revêtement uniforme sur la surface non plane cylindrique. </li><li> Résine photosensible est exposée par un laser à écriture directe système unique (laser tour, un système non commercial développé au Lawrence Livermore National Laboratory) dans le modèle de la forme de bobine désiré (figure 2A). Il s&#39;agit d&#39;une modition de la technique initialement décrite dans Malba et al 14. </li><li> Développer la résine photosensible exposée dans une solution à 1% de carbonate de potassium à 35 ° C. </li><li> Cuivre est galvanisé à travers le masque de résist restante pour former la bobine souhaitée. Le système peut fabriquer à la fois magnétique et les modes de Helmholtz cuivre (hippodrome) (figures 2C et 2D). </li><li> Après électrodéposition de cuivre, retirez le développeur résister à chaud. Enlever la couche de germination de cuivre, suivie par la couche d&#39;adhésion de titane. </li><li> Fixez le tube isolant à l&#39;extrémité du cathéter à l&#39;aide pellicule rétractable pour compléter l&#39;assemblage. Assurez-vous que la pellicule rétractable recouvre le bout enroulé entier. Pour assembler plusieurs axes cathéters placer des structures tubulaires isolants à l&#39;intérieur de l&#39;autre comme le montre la figure 2E. </li><li> Fils de cuivre à travers la lumière de fil de soudure et le microcathéter aux bobines à la pointe. </li><li> Modifier et raccourcir de 6 pi de câble téléphonique RJ11 to 3 pieds de longueur. </li><li> Connecter les fils de cuivre émanant du moyeu d&#39;extrémité arrière du microcathéter à la modification de la ligne téléphonique 3 ft transmission vérin. </li></ol> 2. Configuration bain-marie <ol><li> Faire un petit trou au centre de la face d&#39;une cuvette en plastique environ 5 cm du fond. </li><li> Insérez une 9F Avanti Cordis vasculaire gaine (Cordis Endovascular, Miami Lakes, FL) dans le trou. </li><li> Couper l&#39;extrémité distale de la gaine vasculaire laissant un 4 cm de long morceau s&#39;étendant dans le bassin. </li><li> À l&#39;extrémité de la gaine, fixer une valve hémostatique rotative ou Thuoy-Borst pour stabiliser l&#39;emplacement du microcathéter. </li><li> Remplir le bassin avec de l&#39;eau distillée assurer une immersion complète de l&#39;appareil. </li><li> Insérer le cathéter à embout en spirale à travers la gaine vasculaire et de la vanne. </li><li> Mesurer et noter la longueur effrénée du microcathéter s&#39;étendant de la vanne dans le bain-marie. </li><li> Placez le bain-marie avec microSystème de cathéter à l&#39;intérieur de l&#39;aimant de l&#39;appareil d&#39;IRM et orienter par rapport à l&#39;alésage de l&#39;aimant. </li><li> Branchez le câble téléphonique modifiée 3 pi attaché au cathéter à un 25 pieds RJ11 ligne de transmission de téléphonie par câble à l&#39;aide d&#39;un téléphone 2-way jack. </li><li> Branchez l&#39;autre extrémité du câble 25 pi téléphone à une alimentation Lambda LPD-422A-FM double alimentation régulée pour fournir jusqu&#39;à 1 A de courant de l&#39;appareil. </li><li> Placez les lignes de transmission à travers un guide d&#39;onde et la source d&#39;alimentation en dehors de la salle du scanner MR en dehors de la ligne 5 Gauss. </li></ol> 3. Navire fantôme de configuration <ol><li> Construire un fantôme récipient creux avec une intersection en forme de Y à partir de tubes en caoutchouc avant l&#39;expérimentation. </li><li> Remplissez le fantôme récipient avec une solution 0,0102 M de gadopentétate diméglumine (GdDTPA) (Magnevist, Bayer Healthcare Pharmaceuticals, Montville, New Jersey) dans de l&#39;eau distillée pour créer un contraste entre les vaisseaux fantômes et le fond. </li><li> Assemblez le MicroCatheter système tel que décrit dans les étapes 1.1 à 1.9. Relier le cathéter à l&#39;alimentation électrique et la position comme décrit dans les étapes de 2,9 à 2,11. </li><li> Positionner la pointe du microcathéter à la base de l&#39;ouverture du récipient. </li><li> Placer le fantôme à l&#39;intérieur de l&#39;aimant de l&#39;appareil d&#39;IRM et orienter par rapport à l&#39;alésage de l&#39;aimant. </li></ol> 4. Imagerie par résonance magnétique <ol><li> Effectuer une imagerie avec un système clinique 1.5T MR (Siemens Avanto, SW: Syngo B13, Erlangen, Allemagne; Philips Achieva, SW version 2.1, Cleveland, OH). </li><li> Appliquer &lt;50 mA de courant de visualiser la position de pointe du cathéter. En vertu de l&#39;IRM, un petit moment magnétique sera produite à l&#39;extrémité du cathéter de visualiser un artefact distincte de forme variable en fonction de la bobines sont excitées. </li><li> Appliquer des quantités variables de courant dans la plage de ± 100 mA à partir de la source d&#39;alimentation double Lambda pour les bobines et observer béquillage (figures 3A-3C) dans le ba de l&#39;eaue configuration. Parce que béquillage est presque instantanée, le courant ne doivent être appliqués pour ~ 1-2 secondes pour visualiser déviation maximale. </li><li> Répéter et d&#39;enregistrer applications consécutives de montants de courant. </li><li> Répétez l&#39;étape 4.2, tout en poussant la sonde à la main permettre l&#39;avancement mécanique à travers la cuve (figures 4A et 4B) fantôme. Appliquer le courant au point de branchement de détourner l&#39;extrémité du cathéter dans le vaisseau désiré. Faire avancer le cathéter dans le vaisseau de branche en poussant manuellement l&#39;extrémité de cathéter (Figure 4C). Rétracter le cathéter à la bifurcation de vaisseau et de répétition dans la branche opposée (figure 4D). </li><li> Acquérir des images IRM à l&#39;aide d&#39;un instantané 2D-FLASH séquence (TR = 30 ms, TE = 1,4 ms, une matrice de 256 x 128 et un angle de bascule à 30 °). </li></ol> 5. Les mesures de déflexion Analyser et mesurer les déviations angulaires des images capturées au coursexpériences bain-marie avec diverses applications informatiques (toute 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 a reçu des subventions de Stryker Corporation et est un consultant rémunéré pour Silk Road Medical, Inc

Ici, nous décrivons le protocole de déflexion d&#39;un micro-cathéter dans un appareil d&#39;IRM. Les paramètres clés de la réussite sont une application précise du courant et la mesure de l&#39;angle de déviation. Une mesure inexacte du angle de déflexion est l&#39;erreur la plus probable rencontrées dans ce protocole. Les angles capturées en images par résonance magnétique lors de l&#39;expérience à bain d&#39;eau peuvent différer des valeurs réelles en raison de légères différences dans l&#39;orie...

Procédures endovasculaires effectuées en cours d&#39;utilisation la médecine interventionnelle radiographie l&#39;orientation comme un outil de navigation cathéter dans le système vasculaire pour traiter plusieurs maladies graves, comme la rupture d&#39;anévrisme, accident vasculaire cérébral ischémique, les tumeurs solides, l&#39;athérosclérose et les arythmies cardiaques ciblant plus d&#39;un million de patients par année dans le monde 1 - 5. Avec l&#39;utilisation des produits de contraste, de la navigation à travers le système vasculaire est obtenue par rotation manuelle de l&#39;avancement du cathéter et mécanique par l&#39;intervenant de part 6. Toutefois, la navigation à travers de petits vaisseaux sanguins tortueux à travers de nombreux virages vasculaires devient de plus en plus difficile, en allongeant le temps avant d&#39;atteindre le site cible. Cela pose un problème pour le temps des procédures adaptées telles que la suppression d&#39;un caillot dans un vaisseau sanguin obstrué. En outre, les procédures longues augmenter la dose de rayonnement et créer le potentiel d&#39;événements indésirables 7-11. Toutefois, les procédures endovasculaires réalisée sous magnetic imagerie par résonance magnétique peut apporter une solution. Le fort champ magnétique homogène d&#39;un scanner IRM peut être exploitée pour la navigation extrémité du cathéter par télécommande 12,13. Courant appliqué à une microbobine située à une extrémité du cathéter induit un moment magnétique faible, qui subit un couple tel qu&#39;il s&#39;aligne avec l&#39;alésage de l&#39;appareil d&#39;IRM 13 (figure 1). Si le courant électrique est activé dans une bobine individuelle, l&#39;extrémité du cathéter peut être déviée dans un plan de commande à distance. Si trois bobines à un bout de cathéter sont excitées, déviation extrémité du cathéter peut être réalisé en trois dimensions. Ainsi, la direction magnétique facilité d&#39;un cathéter a le potentiel d&#39;augmenter la vitesse et l&#39;efficacité de la navigation vasculaire dans les procédures endovasculaires, ce qui pourrait réduire les temps d&#39;intervention et d&#39;améliorer les résultats des patients. Dans cette étude, nous avons examiné si le courant appliqué à un cathéter à pointe microbobine endovasculaire peut produire des données fiables et contrôlées deflections de moins de MR-conseils que les tests préliminaires d&#39;études navigation cathéter.

<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

Procédures rayons X guidé par fluoroscopie endovasculaires ont plusieurs limites importantes, y compris la navigation cathéter difficile et l&#39;utilisation des rayonnements ionisants, ce qui peut potentiellement être surmontées à l&#39;aide d&#39;un cathéter orientable magnétique sous la direction de MR. L&#39;objectif principal de ce travail est de développer un micro-cathéter dont l&#39;extrémité peut être contrôlé à distance en utilisant le champ magnétique de l&#39;IRM. Ce protocole vise à décrire les procédures pour appliquer un courant à l&#39;microcathéter microbobine pointe pour produire des déformations cohérentes et contrôlable. Un microbobine a été fabriqué en utilisant la lithographie laser tour sur un cathéter à pointe polyimide endovasculaire. L&#39;expérimentation in vitro a été réalisée dans un bain-marie et le fantôme navire sous la direction d&#39;un système 1,5-T MR en utilisant l&#39;état d&#39;équilibre de précession libre (ASAG) séquençage. Diverses quantités de courant ont été appliqués aux bobines du microcathéter pour produire meadéviations pointe sureable et naviguer dans des fantômes vasculaires. Le développement de ce dispositif fournit une plate-forme pour les essais futurs et la possibilité de révolutionner l&#39;environnement IRM interventionnelle endovasculaire.

Du protocole décrit ci-dessus, un angle de déviation entre 0 et 90 degrés doit être observée à partir de l&#39;application 50-300 mA de courant délivré simultanément aux deux bobines d&#39;un électro-aimant et le système combiné de Helmholtz microcathéter bobine (2E figure). Une augmentation du courant appliqué devrait se traduire par une augmentation de l&#39;angle de déviation microcathéter, tandis qu&#39;une inversion de polarité de courant doit se traduire par déviation dans la dir...

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

Courant appliqué à un micro-cathéter endovasculaire avec pointe microbobine faite par laser Tour lithographie peut atteindre déviations contrôlables en vertu de résonance (MR) de guidage magnétique, ce qui peut améliorer la vitesse et l&#39;efficacité de la navigation de la vascularisation au cours de diverses procédures endovasculaires.

Magnétique assistée à distance de déviation contrôlée Astuce Microcatheter sous imagerie par résonance magnétique

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

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12.3K vues.  University of California, San Francisco. Courant appliqué à un micro-cathéter endovasculaire avec pointe microbobine faite par laser Tour lithographie peut atteindre déviations contrôlables en vertu de résonance (MR) de guidage magnétique, ce qui peut améliorer la vitesse et l'efficacité de la navigation de la vascularisation au cours de diverses procédures endovasculaires.

Vidéo: 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).

Méthodologie élastographie par résonance magnétique pour l&#39;évaluation des tissus Conçu croissance 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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Bio-ingénierie

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.

Déclenchement à distance magnétique de sondes micrométriques pour<em&gt; In situ</em&gt; Cartographie 3D de biofilms bactériens Propriétés physiques

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.

Spécialement conçu à base de laser appareils de chauffage à libération déclenchée de cisplatine de thermosensible liposomes avec guidage par l&#39;image par résonance magnétique

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.

Magnétique alternatif microgels de gélatine hybride sensible au champ de libération contrôlée de médicaments

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.

Numérisation rapide résonance paramagnétique électronique ouvre de nouvelles voies pour l&#39;imagerie physiologiquement Paramètres importants<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.

Lévitation magnétique Couplé avec imagerie portable et d&#39;analyse pour le diagnostic de la maladie

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.

Poly magnétique et thermosensible (<em&gt; N</em&gt; Microgels à base de isopropylacrylamide) pour une libération contrôlée magnétiquement déclenchée

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.

Soutien métabolique des excisées, les tissus de cerveau vivants lors de l’Acquisition de la microscopie par résonance magnétique

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.

Mesurer la dépendance au champ magnétique de relaxation spin-lattice de l'hyperpolarisé [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.

Imagerie à haute résolution de la dynamique nucléaire dans les cellules vivantes sous contrainte de traction uniaxiale

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