Pallav Kolli, Fabio Settecase, Amans Matteo, e Robert Taylor da UCSF, Tim Roberts University of Pennsylvania Enti finanziatori NIH National Heart Lung Blood Institute (NHLBI) Award (M. Wilson): 1R01HL076486 Società Americana di Neuroradiologia ricerca e Education Foundation Scholar Award (S. Hetts) NIH Istituto Nazionale di Biomedical Imaging e Bioingegneria (NIBIB) Award (S. Hetts): 1R01EB012031

1. MICROTUBOLARI Fabrication <ol><li> Ottenere un microcatetere disponibile in commercio (ad esempio, 2.3F Rapid Transit Cordis catetere neurovascolare, Raynham, MA) per un substrato. </li><li> Assicurarsi cateteri non hanno componenti ferrosi, sono considerati MR-safe, e la gamma di dimensioni 2,3-3,0 F. </li><li> Polverizzare una strato di adesione di titanio seguito da uno strato di rame di un seme al mm 1 a 2 Tubo OD isolante. Materiali possibili includono poliimmide o allumina (ORtech Ceramiche avanzate, Sacramento, CA). </li><li> Electrodeposit uno strato di fotoresist positivo con Shipley PEPR-2400 (attualmente in vendita da Dow Chemical con il nome Intervia 3D-P). Risultati elettrodeposizione in un rivestimento uniforme sulla superficie non planare cilindrica. </li><li> Fotoresist è esposto da un laser unico sistema di scrittura diretta (laser tornio, non commerciale sistema sviluppato presso il Lawrence Livermore National Laboratory) nel modello della forma della bobina desiderata (Figura 2A). Questa è una modificazione della tecnica descritto originariamente in Malba et al. 14 </li><li> Sviluppare il photoresist esposto in una soluzione all&#39;1% di carbonato di potassio a 35 ° C. </li><li> Rame placcato è attraverso il restante maschera di resist per formare la bobina desiderata. Il sistema può fabbricare sia solenoide e di Helmholtz (pista) i modelli di rame (Figure 2C e 2D). </li><li> Dopo elettrodeposizione di rame, rimuovere il resist con lo sviluppatore caldo. Rimuovere lo strato di germinazione di rame, seguita dalla strato di adesione di titanio. </li><li> Fissare il tubo isolante per la punta del catetere con termoretraibile per completare il montaggio. Assicurarsi che il termoretraibile copre tutta la punta a spirale. Per assemblare multiasse cateteri posizionare strutture tubo isolante dentro l&#39;altro come mostrato nella Figura 2E. </li><li> Fili di rame filo attraverso il lume del microcatetere e saldare le bobine alla punta. </li><li> Modifica e accorciare un ft 6 cavo telefonico RJ11 to 3 m di lunghezza. </li><li> Collegare i fili di rame provenienti dal nodo back-end del microcatetere alla modificato 3 linea telefonica di trasmissione ft jack. </li></ol> 2. Bagnomaria Setup <ol><li> Praticare un foro al centro del lato di una bacinella di plastica di circa 5 cm dal fondo. </li><li> Inserire un 9F Avanti Cordis guaina vascolare (Endovascular Cordis, Miami Lakes, FL) attraverso il foro. </li><li> Tagliare la punta distale della guaina vascolare lasciando a 4 cm di lunghezza pezzo estende al bacino. </li><li> Alla fine della guaina, collegare una valvola emostatica rotante o Thuoy-Borst per stabilizzare la posizione del microcatetere. </li><li> Riempire la vasca con acqua distillata garantire la completa immersione dell&#39;apparato. </li><li> Inserire il catetere con la punta a spirale attraverso la guaina vascolare e la valvola. </li><li> Misurare e registrare la lunghezza sfrenata del microcatetere si estende dalla valvola al bagnomaria. </li><li> Posizionare il bagnomaria con microSistema di catetere all&#39;interno del magnete dello scanner MR e orientare rispetto al diametro del magnete. </li><li> Collegare il cavo telefonico modificato 3 metri collegato al catetere a un ft 25 RJ11 linea di trasmissione cavo telefonico con un 2 vie presa telefonica. </li><li> Collegare l&#39;altra estremità del cavo di 25 piedi telefono a una Lambda LPD-422A-FM doppia alimentazione regolata per fornire fino a 1 A di corrente al dispositivo. </li><li> Posizionare le linee di trasmissione attraverso una guida d&#39;onda e la sorgente di alimentazione esterna della camera scanner MR fuori della linea 5 Gauss. </li></ol> 3. Impostazione della nave fantasma <ol><li> Costruire un fantasma nave con un cavo a Y intersezione partire da un tubo di gomma prima della sperimentazione. </li><li> Riempire il fantasma nave con una soluzione 0,0102 M di gadopentetato dimeglumina (GdDTPA) (Magnevist, Bayer Healthcare Pharmaceuticals, Montville, New Jersey) in acqua distillata per creare un contrasto tra le navi fantasma e lo sfondo. </li><li> Montare il MicroCsistema atheter come indicato nei passi da 1.1 a 1.9. Collegare il catetere per l&#39;alimentazione e la posizione come descritto nelle fasi 2,9-2,11. </li><li> Posizionare la punta del microcatetere alla base dell&#39;apertura nave. </li><li> Posizionare il fantasma all&#39;interno del magnete dello scanner MR e orientare rispetto al diametro del magnete. </li></ol> 4. Risonanza Magnetica <ol><li> Eseguire l&#39;imaging con un 1.5T clinica MR sistema (Siemens Avanto, SW: syngo B13, Erlangen, Germania, Philips Achieva, SW versione 2.1, Cleveland, OH). </li><li> Applica &lt;50 mA di corrente per visualizzare la posizione della punta del catetere. Sotto MRI, un piccolo momento magnetico sarà prodotto sulla punta del catetere di visualizzare un artefatto distinto di varia forma a seconda di quale sono eccitati bobine. </li><li> Applicare quantità variabili di corrente nel range di ± 100 mA dalla sorgente Lambda doppia alimentazione alle bobine e osservare deflessione tip (Figure 3A-3C) in ba acquath installazione. Perché deflessione punta è quasi istantanea, la corrente può essere applicato solo per ~ 1-2 sec per visualizzare deformazione massima. </li><li> Ripetere e registrare le applicazioni consecutive di importi stabiliti di corrente. </li><li> Ripetere passaggio 4,2 e contemporaneamente premere il catetere a mano consentendo l&#39;avanzamento meccanico attraverso il vaso phantom (Figure 4A e 4B). Applicare corrente al punto di diramazione per deflettere la punta del catetere nel vaso desiderato. Avanzare il catetere nel vaso ramo manualmente spingendo l&#39;estremità del catetere (Figura 4C). Ritrarre il catetere alla biforcazione nave e ripetizione nel ramo opposto (Figura 4D). </li><li> Acquisire immagini RM con un 2D snapshot-FLASH sequenza (TR = 30 msec, TE = 1.4 msec, una matrice di 256 x128 e flip angle ~ 30 °). </li></ol> 5. Deflessione Misure Analizzare e misurare le deviazioni angolari di immagini acquisite duranteesperimenti bagno d&#39;acqua con varie applicazioni informatiche (qualsiasi Digital Imaging 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 ha ricevuto concedere il sostegno di Stryker Corporation ed è un consulente pagato per Silk Road Medical, Inc.

Qui si descrive il protocollo di deflessione di un microcatetere in uno scanner MR. I parametri chiave per il successo sono l&#39;applicazione precisi di corrente e misura di angolo di deviazione. Misurazione accurata del angolo di deviazione è l&#39;errore più probabile incontrato in questo protocollo. Gli angoli catturati in immagini MR durante l&#39;esperimento bagnomaria possono differire dai valori reali dovute a lievi differenze di orientamento da cui è posizionato il supporto rispetto al diametro del magnete. ...

Procedure endovascolari eseguite in medicina interventistica uso x-ray di orientamento come strumento per la navigazione attraverso il catetere vascolare per il trattamento di varie malattie importanti, come aneurisma cerebrale, ictus ischemico, tumori solidi, l&#39;aterosclerosi e le aritmie cardiache destinati a più di un milione di pazienti ogni anno in tutto il mondo 1 - 5. Con l&#39;uso di mezzi di contrasto, la navigazione attraverso vascolare è ottenuta attraverso la rotazione manuale del catetere avanzamento e meccanica dal interventista mano 6. Tuttavia, la navigazione attraverso piccoli vasi sanguigni tortuosi intorno molte curve vascolari diventa sempre più difficile, allungando il tempo prima di raggiungere il sito di destinazione. Questo pone un problema per time-sensitive procedure come la rimozione di un coagulo in un vaso sanguigno occluso. Inoltre, procedure prolungate aumentare la dose di radiazioni e creare la possibilità di eventi avversi 7-11. Tuttavia, le procedure endovascolari eseguite sotto magnetic risonanza può fornire una soluzione. Il forte campo magnetico omogeneo di uno scanner MRI può essere sfruttato per la navigazione del catetere con il telecomando 12,13. Corrente applicata a un MICROTUBOLARI situato in una punta di catetere induce un piccolo momento magnetico, che sperimenta una coppia come si allinea con il foro dello scanner MRI 13 (Figura 1). Se la corrente elettrica viene attivata in una bobina singola, il catetere può essere deviato in un piano tramite telecomando. Se tre bobine ad una punta di catetere vengono eccitati, punta deflessione del catetere può essere realizzato in tre dimensioni. Così, lo sterzo magneticamente agevolato di un catetere ha il potenziale di aumentare la velocità e l&#39;efficacia di navigazione vascolare nelle procedure endovascolari, che potrebbe ridurre i tempi di procedura e migliorare i risultati dei pazienti. In questo studio, abbiamo esaminato se la corrente applicata ad un MICROTUBOLARI punta di catetere endovascolare può produrre affidabile e controllato deflections in MR-guida come test preliminari degli studi di navigazione del catetere.

<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

Procedure di fluoroscopia a raggi X a guida endovascolari hanno diverse limitazioni significative, tra cui la navigazione del catetere difficile e l&#39;uso di radiazioni ionizzanti, che potenzialmente possono essere superati utilizzando un catetere magneticamente orientabile sotto la guida di MR. L&#39;obiettivo principale di questo lavoro è quello di sviluppare un microcatetere la cui punta può essere controllato a distanza mediante il campo magnetico dello scanner MR. Questo protocollo si propone di descrivere le modalità di applicazione di corrente al MICROTUBOLARI punta microcatetere per produrre deviazioni coerenti e controllabili. Un MICROTUBOLARI è stato fabbricato utilizzando la litografia laser su un tornio poliimmide punta del catetere endovascolare. Test in vitro è stato eseguito in un bagno d&#39;acqua e nave fantasma sotto la guida di un 1,5-T MR come stato stazionario senza precessione (SSFP) sequenziamento. Varie quantità di corrente sono stati applicati alle bobine del microcatetere per produrre MEAdeviazioni punta sureable e navigare in fantasmi vascolari. Lo sviluppo di questo dispositivo fornisce una piattaforma per test futuri e l&#39;opportunità di rivoluzionare l&#39;ambiente interventistica endovascolare MRI.

Dal protocollo sopra descritto, un angolo di deflessione tra 0 e 90 gradi deve osservare dall&#39;applicazione di 50-300 mA di corrente erogata simultaneamente entrambe le bobine di un solenoide combinato e sistema di bobine di Helmholtz microcatetere (Figura 2E). Un aumento di corrente applicata dovrebbe risultare in un aumento dell&#39;angolo di deflessione microcatetere, mentre un&#39;inversione di polarità corrente dovrebbe comportare deflessione nella direzione opposta come rilevato con corrente p...

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

Corrente applicata ad un microcatetere endovascolare con punta MICROTUBOLARI fatta da litografia laser tornio può ottenere deviazioni controllabili in risonanza magnetica (MR) di orientamento, che può migliorare la velocità e l&#39;efficacia di navigazione dei vasi durante le varie procedure endovascolari.

Magneticamente-Assisted Remote Controlled Suggerimento Flessione Microcatetere in Risonanza Magnetica

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

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12.3K Views.  University of California, San Francisco. Corrente applicata ad un microcatetere endovascolare con punta MICROTUBOLARI fatta da litografia laser tornio può ottenere deviazioni controllabili in risonanza magnetica (MR) di orientamento, che può migliorare la velocità e l'efficacia di navigazione dei vasi durante le varie procedure endovascolari.

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).

Metodologia Elastografia risonanza magnetica per la valutazione dei Tissue Engineered Construct crescita

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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Bioingegneria

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.

Azionamento a distanza magnetica micrometrici Sonde per<em&gt; In situ</em&gt; Mappatura 3D di biofilm batterici Proprietà fisiche

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.

Appositamente studiata apparecchi di riscaldamento a base laser per la Release Innescata di Cisplatino da termosensibile liposomi con Risonanza Magnetica Guidance Immagine

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 microgel ibrida Gelatina di campo magnetico-Responsive per Controlled Drug uscita

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

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

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

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

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

Rapid Scan paramagnetica elettronica Risonanza apre nuove strade per l&#39;imaging Fisiologicamente parametri importanti<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.

Levitazione magnetica Accoppiato con Imaging portatile e analisi per la malattia di diagnostica

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.

Poli sensibile magnetico e termico (<em&gt; N</em&gt; -isopropilacrilammide) per il rilascio controllato magneticamente attivato

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.

Supporto metabolico di asportato, tessuti di cervello viventi durante l'acquisizione di microscopia a risonanza magnetica

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.

Misurazione della dipendenza da campo magnetico di rilassamento Spin-Lattice di iperpolarizzato [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.

Imaging ad alta risoluzione di dinamiche nucleari in cellule vive sotto tensione uniassiale

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