Pallav Kolli, Fabio Settecase, Mateus Amans, e Robert Taylor da UCSF, Tim Roberts, da Universidade da Pensilvânia Fontes de Financiamento NIH National Heart Lung Blood Institute (NHLBI) Award (M. Wilson): 1R01HL076486 Sociedade Americana de Neurorradiologia Pesquisa e Fundação de Educação Prêmio Acadêmico (S. Hetts) NIH Instituto Nacional de Imagens Biomédicas e Bioengenharia (NIBIB) Award (S. Hetts): 1R01EB012031

1. Micromolas Fabricação <ol><li> Obter um microcateter comercialmente disponíveis (por exemplo, 2.3F Rapid Transit Cordis Cateter Neurovascular, Raynham, MA) para um substrato. </li><li> Garantir cateteres não têm componentes ferrosos, são considerados MR-seguro, e variam em tamanho 2,3-3,0 F. </li><li> Sputter uma camada de adesão de titânio seguido por uma camada de sementes de cobre até um milímetro 1-2 OD tubo isolante. Os materiais possíveis incluem poliimida, ou alumina (Ortech avançada Ceramics, Sacramento, CA). </li><li> Electrodepositar uma camada foto-resistente positivo usando Shipley PEPR-2400 (sendo vendida pela DOW Chemical sob o nome Intervia 3D-P). Resultados de electrodeposição em um revestimento uniforme sobre a superfície não plana cilíndrica. </li><li> Fotossensível é exposta por um único sistema de laser de escrita directa (laser torno, um sistema não-comercial desenvolvido no Lawrence Livermore National Laboratory) no padrão da forma desejada da bobina (Figura 2A). Esta é uma modificaçãoção da técnica originalmente descrita em Malba et al 14. </li><li> Desenvolver a fotorresiste exposto de uma solução a 1% de carbonato de potássio a 35 ° C. </li><li> O cobre é electrodepositado através da máscara resistir remanescente para formar a bobina desejado. O sistema pode fabricar tanto solenóide e os padrões de Helmholtz (pista) de cobre (Figuras 2C e 2D). </li><li> Depois de eletrodeposição de cobre, retire a resistir com o desenvolvedor quente. Remover a camada de semente de cobre, seguida pela camada de adesão de titânio. </li><li> Anexar o tubo de isolamento para a ponta do cateter através de invólucro por contracção para completar a montagem. Certifique-se que o envoltório do psiquiatra cobre a ponta enrolada inteiro. Para montar multi-eixo cateteres colocar as estruturas de tubo de isolamento no interior uns dos outros, como mostrado na Figura 2E. </li><li> Tópico fios de cobre através do lúmen do microcateter e solda para as bobinas na ponta. </li><li> Modificar e encurtar um 6 pés RJ11 cabo de telefone to ft 3 em comprimento. </li><li> Conectar os fios de cobre que emanam do cubo extremidade traseira do microcateter a 3 pés de telefone de linha de transmissão modificada tomada. </li></ol> 2. Configuração banho-maria <ol><li> Fazer um pequeno orifício no centro da face de um recipiente de plástico a cerca de 5 cm do fundo. </li><li> Insira um 9F Avanti Cordis bainha vascular (Cordis Endovascular, Miami, FL) através do orifício. </li><li> Cortar a extremidade distai da bainha vascular deixando um pedaço 4 cm de comprimento, que se estende em a bacia. </li><li> No final da bainha, coloque uma válvula hemostática rotativa ou Thuoy-Borst para estabilizar a localização do microcateter. </li><li> Encher o recipiente com água destilada, assegurando completa submersão do aparelho. </li><li> Inserir o cateter com ponta em espiral através da bainha vascular e da válvula. </li><li> Medir e registar a duração irrestrita do microcateter que se estende desde a válvula para o banho de água. </li><li> Coloque o banho de água com microsistema de cateter no interior do íman do scanner de MR e orientar em relação ao orifício do íman. </li><li> Conecte o cabo de telefone modificado 3 pés ligado ao cateter para a 25 RJ11 linha telefônica de transmissão pés cabo usando um 2-way conector de telefone. </li><li> Ligue a outra extremidade do cabo de telefone 25 pés a uma fonte de alimentação Lambda LPD-422A-FM dupla regulado para fornecer até 1 A de corrente para o dispositivo. </li><li> Coloque as linhas de transmissão por meio de uma guia de onda e a fonte de alimentação para fora da sala de scanner MR fora da linha de Gauss 5. </li></ol> 3. Configuração navio fantasma <ol><li> Construir um navio fantasma oco com uma intersecção em forma de Y a partir de tubo de borracha antes da experimentação. </li><li> Preencha o fantasma vaso com uma solução 0,0102 M de gadopentetato dimeglumina (GdDTPA) (Magnevist, Bayer Healthcare Pharmaceuticals, Montville, Nova Jersey) em água destilada para criar um contraste entre os vasos fantasmas e de fundo. </li><li> Monte o MicroCatheter sistema como descrito nas etapas 1.1 a 1.9. Conectar o catéter à fonte de alimentação e da posição, tal como descrito nos passos 2,9-2,11. </li><li> Posicionar a ponta do microcateter na base da abertura do vaso. </li><li> Coloque o fantasma dentro do íman do scanner de MR e orientar em relação ao orifício do íman. </li></ol> 4. Imagem por Ressonância Magnética <ol><li> Realizar imagem com um 1.5T clínica sistema MR (Siemens Avanto, SW: Syngo B13, Erlangen, Alemanha; Philips Achieva, SW versão 2.1, Cleveland, OH). </li><li> Aplicar &lt;50 mA de corrente a visualizar a posição da ponta do cateter. Sob MRI, um pequeno momento magnético será produzida na ponta do cateter para visualizar um artefato distinto de variar dependendo da forma que as bobinas são energizadas. </li><li> Aplicar quantidades variáveis ​​de corrente no intervalo de ± 100 mA da fonte de alimentação de dupla Lambda para as bobinas de deflexão e observar ponta (Figuras 3A-3C), no ba de águaª configuração. Porque a deflexão da ponta é quase instantânea, a corrente só necessita de ser aplicado durante 1-2 s ~ para visualizar deflexão máxima. </li><li> Repetir e gravar aplicações consecutivas de montantes de corrente. </li><li> Repetir o passo 4,2, ao mesmo tempo que empurra o cateter à mão permitindo avanço mecânico através do vaso fantasma (Figuras 4A e 4B). Aplicar corrente no ponto de ramificação para deflectir a ponta do cateter para dentro do vaso desejado. Avançar o cateter dentro do vaso por ramo manualmente empurrando a extremidade do cateter (Figura 4C). Retrair o cateter para a bifurcação do vaso e repetir no ramo oposto (Figura 4D). </li><li> Adquirir imagens de RM, utilizando uma sequência instantâneo FLASH-2D (TR = 30 ms, TE = 1,4 ms, uma matriz de 256 x128 e ângulo aleta ~ 30 °). </li></ol> 5. Medidas de deflexão Analisar e medir deformações angulares de imagens capturadas duranteexperimentos de água de banho com várias aplicações informáticas (qualquer imagem digital e Comunicações em Medicina (DICOM) Viewer).

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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 recebeu apoio financeiro da Stryker Corporation e é um consultor pago para Silk Road Medical, Inc.

Aqui descrevemos o protocolo para a deflexão de um microcateter em um scanner de MR. Os parâmetros-chave para o sucesso são precisas aplicação de corrente e medição do ângulo de deflexão. Medição imprecisa de ângulo de deflexão é o erro mais provável encontrada neste protocolo. Os ângulos capturados em imagens de RM banho de água durante a experiência podem diferir dos valores reais devido a pequenas diferenças na orientação em que o meio é posicionado em relação ao orifício do íman. Para resol...

Procedimentos endovasculares realizados em medicina intervencionista orientação utilização de raio-x como uma ferramenta para navegação através de cateter vascular para tratar várias doenças graves, tais como aneurisma cerebral, acidente vascular cerebral isquêmico, tumores sólidos, aterosclerose e arritmias cardíacas para mais de um milhão de pacientes por ano em todo o mundo 1 - 5. Com a utilização de meios de contraste, a navegação através da vasculatura é conseguido através de rotação manual do avanço do cateter e mecânica, pelo intervencionista da mão 6. No entanto, a navegação através de pequenos vasos sanguíneos tortuosos em torno de muitas curvas vascular torna-se cada vez mais difícil, alongando o tempo antes de atingir o local do alvo. Isso representa um problema para sensíveis ao tempo de procedimentos, tais como a remoção de um coágulo de sangue num vaso ocluso. Além disso, procedimentos prolongados aumentar a dose de radiação e criar o potencial para eventos adversos 7-11. No entanto, os procedimentos endovasculares realizados sob magnetic ressonância pode oferecer uma solução. O campo magnético forte homogênea de um scanner de ressonância magnética podem ser exploradas para a navegação ponta do cateter por controle remoto 12,13. Corrente aplicada a um micromolas localizado a uma ponta do cateter induz um momento magnético, que experimenta um binário, uma vez que se alinha com o furo do scanner de IRM 13 (Figura 1). Se a corrente eléctrica é activado em uma bobina individual, a ponta do cateter pode ser desviado para um plano por controle remoto. Se três bobinas a uma ponta do cateter são energizados, a deflexão da ponta do cateter pode ser conseguido em três dimensões. Assim, direcção magneticamente facilitada de um cateter tem o potencial para aumentar a velocidade e eficácia da navegação vascular em procedimentos endovasculares, que poderia reduzir o tempo de processo e melhorar os resultados do paciente. No presente estudo, examinou-se se a corrente aplicada a um cateter com ponta de micromolas endovascular pode produzir deflecti fiável e controladaons sob orientação MR-como testes preliminares de estudos de navegação do cateter.

<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

Procedimentos de raios-X fluoroscopia guiada endovasculares têm várias limitações significativas, incluindo a navegação cateter difícil e uso de radiação ionizante, o que pode, potencialmente, ser superado através de um cateter magneticamente dirigível sob a orientação do MR. O objectivo principal deste trabalho é a de desenvolver um microcateter cuja ponta pode ser controlado remotamente com o campo magnético do scanner de MR. Este protocolo tem como objetivo descrever os procedimentos para a aplicação de corrente para o microcateter micromolas de ponta para produzir desvios consistentes e controlável. Uma micro foi fabricado usando laser litografia em torno de um cateter poliimida de ponta endovascular. Testes in vitro foi realizada em banho-maria e fantasma navio sob a orientação de um sistema de RM de 1,5 T com estado estável livre de precessão (SSFP) seqüenciamento. Várias quantidades de corrente foram aplicados às bobinas do microcateter para produzir measureable desvios ponta e navegar em fantasmas vasculares. O desenvolvimento deste dispositivo fornece uma plataforma para testes de futuro e oportunidade de revolucionar o ambiente intervencionista endovascular de ressonância magnética.

A partir do protocolo acima descrito, com um ângulo de deflexão entre 0 e 90 graus deve-se observar a partir de aplicação de 50-300 mA de corrente entregue simultaneamente a ambas as bobinas de um solenóide combinado e sistema de microcateter bobina de Helmholtz (Figura 2E). Um aumento da corrente aplicada deve resultar num aumento do ângulo de deflexão microcateter, enquanto que a inversão de polaridade de corrente deve resultar em desvio na direcção oposta, como observado com corrente positi...

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 aplicada a um microcateter endovascular com ponta micromolas feita por laser litografia torno pode alcançar deflexões controláveis ​​sob orientação de ressonância magnética (MR), que pode melhorar a velocidade e a eficácia de navegação da vasculatura durante vários procedimentos endovasculares.

Magneticamente Assistida deflexão da ponta Remote Controlled microcateter em Imagem por Ressonância 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 visualizações.  University of California, San Francisco. Corrente aplicada a um microcateter endovascular com ponta micromolas feita por laser litografia torno pode alcançar deflexões controláveis ​​sob orientação de ressonância magnética (MR), que pode melhorar a velocidade e a eficácia de navegação da vasculatura durante vários procedimentos endovasculares.

Vídeo: 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 por Ressonância Magnética para a Avaliação de engenharia de tecidos Crescimento 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 ...

Bioengenharia

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.

Atuação Remoto magnética de micrométricas para Sondas<em&gt; In situ</em&gt; Mapping 3D de bactérias biofilme Propriedades 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.

Customizado aparelho de aquecimento à base de laser para lançamento acionado de cisplatina de termossensível lipossomas com Ressonância Magnética Orientação Imagem

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 microgéis de gelatina híbrido Campo-Responsive magnética para controlada de fármacos de libertação

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.

Rápida digitalização ressonância paramagnética eletrônica abre novos caminhos para criação de imagens fisiologicamente parâmetros importantes<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.

Levitação magnética Juntamente com imagem Portátil e Análise para a doença Diagnostics

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 (Magnetic and Thermal-sensitive Poly)<em&gt; N</em&gt; Microgels com base em isopropilacrilamida) para liberação controlada com disparo magnético

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.

Suporte metabólico de extirpado, tecidos de cérebro vivos durante a aquisição de microscopia de ressonância 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.

Medindo a dependência do campo magnético do abrandamento da girar-estrutura de Hyperpolarizado [1-13C] piruvato

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.

Imagem latente de alta resolução da dinâmica nuclear em pilhas vivos a tensão elástica uniaxial

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