Pallav Kolli, 파비오 Settecase, 매튜 Amans, 그리고 펜실베니아 대학에서 UCSF, 팀 로버츠의 로버트 테일러 자금 소스 NIH 국립 심장 폐 혈액 연구소 (NHLBI) 상 (M. 윌슨) : Neuroradiology 연구 및 교육 재단 학술 상 1R01HL076486 미국 협회 (S. Hetts) 생명 이미징 및 생물 공학의 NIH 국립 연구소 (NIBIB) 상 (S. Hetts) : 1R01EB012031

1. Microcoil 제작 <ol><li> 기판의 상용화 microcatheter (예를 들면 2.3F 쾌속 교통 Cordis Neurovascular 카테터, Raynham, MA) 구합니다. </li><li> 카테터 크기가 2.3-3.0 F.를 더 철 부품, MR-안전한 것으로 간주되며, 범위를가 없습니다 확인 </li><li> 1-2밀리미터 OD 절연 튜브 께 구리 시드 층 다음에 티타늄 접착 레이어를 스퍼터. 가능한 자료는 폴리이 미드 또는 알루미나 (Ortech 고급 도자기, 새크라멘토, CA)가 포함되어 있습니다. </li><li> 쉬 플리의 PEPR-2400을 (현재의 이름 Intervia 3D-P에서 DOW 케미칼에서 판매되는)를 사용하여 긍정적 인 포토 레지스트 층을 Electrodeposit. 비평 원통형 표면에 균일 한 코팅에 전착 결과입니다. </li><li> 포토 레지스트는 원하는 코일 형태 (그림 2A)의 패턴에서 독특한 레이저 직접 쓰기 시스템 (레이저 선반, 로렌스 리버모어 국립 연구소에서 개발 비상업적 시스템)에 의해 노출됩니다. 이 modifica입니다기술의 기 원래 Malba 외에 설명되어 있습니다. 14 </li><li> 35 ° C.에 탄산 칼륨의 1 % 용액에 노출 된 포토 레지스트를 개발 </li><li> 구리는 원하는 코일을 형성 남은 저항 마스크를 통해 전기 도금되어 있습니다. 이 시스템은 솔레노이드와 Helmholtz (경주) 구리 패턴 (그림 2C와 2D)을 모두 조작 할 수 있습니다. </li><li> 구리 전착 후, 따뜻한 개발자와 저항을 제거합니다. 티타늄 접착 층 다음에 구리 시드 층을 제거합니다. </li><li> 조립을 완료 수축 포장을 사용하여 카테터 팁에 절연 튜브를 연결합니다. 정신과 랩이 전체 코일 팁이 포함되어 있는지 확인합니다. 그림 2E과 같이 다중 축 카테터를 조립하려면 서로 내부에 절연 튜브 구조를 배치합니다. </li><li> 나사 구리 끝에서 코일에 microcatheter 및 납땜의 내강을 통해 선. </li><li> 6피트 RJ11 전화 케이블 t을 수정하고 단축길이 O 3피트 </li><li> microcatheter의 백 엔드 허브에서 수정 된 3피트 전화 잭 전송 라인에 나오는 구리 전선을 연결합니다. </li></ol> 2. Waterbath 설정 <ol><li> 아래에서 5cm에 대한 플라스틱 분지의 측면의 중앙에 작은 구멍을 만듭니다. </li><li> 구멍을 통해 9 층 벤티 Cordis 혈관의 피복을 (Endovascular Cordis, 마이애미 호수, FL)를 넣습니다. </li><li> 분지에 확장 4cm 길이 조각을 남겨 혈관 피복의 말초 끝을 자른다. </li><li> 칼집의 끝에서 microcatheter의 위치를​​ 안정화하기 위해 회전 hemostatic 또는 Thuoy-Borst 밸브를 첨부합니다. </li><li> 증류수는 장치의 침수 완전한 보장과 분지를 입력합니다. </li><li> 혈관 칼집과 밸브를 통해 코일 팁과 카테터를 삽입합니다. </li><li> 측정하고의 밸브에서 waterbath까지 연장 microcatheter의 억제 길이를 기록합니다. </li><li> 마이크로으로 waterbath를 배치자석의 구멍에 대해 MR 스캐너와 방향의 자​​석 내 카테 테르 시스템입니다. </li><li> 2 방법 전화 잭을 사용하여 25피트 RJ11 전화 케이블 전송 라인에 카테터에 부착 수정 3피트 전화 케이블을 연결합니다. </li><li> 장치에 전류의 1 A까지 광고를 게재 할 수있는 람다 LPD-422A-FM 이중 규제 전원 공급 장치에 25 피트 전화 케이블의 다른 쪽 끝을 연결합니다. </li><li> 5 가우스 라인 이외의 MR 스캐너 룸 이외의 도파관과 전원을 통해 전송 라인을 놓으십시오. </li></ol> 3. 선박 환상의 설정 <ol><li> 실험하기 전에 고무 튜브에서 Y 자형 교차로와 빈 용기 팬텀를 구성합니다. </li><li> 유령 선박과 배경 사이의 대비를 만들 증류수에 gadopentetate dimeglumine (GdDTPA) (Magnevist, 바이엘 헬스 케어 제약, Montville, 뉴저지)의 0.0102 M 솔루션으로 선박 팬텀을 입력합니다. </li><li> microc를 조립atheter 시스템은 1.9 단계 1.1에서 설명. 로 2.11에 단계 2.9에 설명 된 전원 공급 장치와 위치로 카테터를 연결합니다. </li><li> 선박 운영의 기본에 microcatheter의 끝을 배치합니다. </li><li> 자석의 내경에 대하여 MR 스캐너와 방향의 자​​석 내에서 팬텀를 놓습니다. </li></ol> 4. 자기 공명 영상 <ol><li> 1.5T 임상 MR 시스템 (:; 필립스 Achieva, SW 릴리스 2.1, 클리블랜드, OH Syngo B13, 에를 랑겐, 독일 지멘스 Avanto, SW)와 이미징을 수행합니다. </li><li> 카테 테르 팁 위치를 시각화하기 위해 현재의 &lt;50mA을 적용합니다. MRI에서 작은 자석 순간 코일이 활력하는에 따라 모양이 변하는의 독특한 유물을 시각화하는 카테 테르 팁에서 생산됩니다. </li><li> 람다 듀얼 전원에서 코일에 ± 100mA의 범위에 현재의 변수 금액을 적용하고 물 바에서 팁 편향을 (그림 3A-3C) 관찰일 설정. 팁 편향이 거의 즉시이기 때문에, 전류는 최대 편향를 시각적으로 ~ 1-2에 초를 적용 만하면됩니다. </li><li> 반복과 현재의 설정 금액의 연속 응용 프로그램을 기록합니다. </li><li> 동시에 혈관 팬텀 (그림 4A 및 4B)를 통해 기계 발전을 허용 손으로 카테터를 밀어 동안 4.2 단계를 반복합니다. 원하는 용기에 카테 테르 팁을 편향하는 분기점에서 현재 적용됩니다. 수동으로 카테 테르 끝 (그림 4C)를 밀어 지점 용기에 카테 테르을 부활 시켰습니다. 반대 지점에있는 선박 분기와 반복 (그림 4D)에 카테터를 철회. </li><li> 2D 스냅 샷 - FLASH 시퀀스 (TR = 30 밀리 초, TE = 1.4 밀리 초, 256 x128의 행렬과 플립 각도 ~ 30 °)를 사용하여 MR 이미지를 취득. </li></ol> 5. 편향 측정 동안 캡처 된 이미지의 각도 편향을 분석하고 측정다양한 컴퓨터 응용 프로그램 (의학의 모든 디지털 이미징 및 통신 (DICOM) 뷰어)와 물 목욕 실험.

<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>

박사 Hetts는 스트라이커 Corporation의 지원을 부여받은 실크로드 의료 주식회사의 유료 컨설턴트했습니다

여기 MR 스캐너에서 microcatheter의 편향에 대한 프로토콜을 설명합니다. 성공을위한 주요 매개 변수는 현재와 편향 각도의 측정의 정확한 응용 프로그램입니다. 편향 각도의 부정확 한 측정이 프로토콜에 발생한 가장 가능성이 오류가 발생합니다. waterbath 실험 기간 동안 MR 이미지를 캡처 각도 매체는 자석의 내경과 관련하여 위치하는이 방향으로 약간의 차이로 인해 실제 값과 다를 수 있습니다. ?...

이러한 뇌 동맥류, 허혈성 뇌졸중, 고체 종양, 죽상 경화증 전세계 일년 당 100 만 개 이상의 환자를 대상 심장 arrhythmias과 같은 몇 가지 주요 질병을 치료 vasculature을 통해 카테터 탐색을위한 도구로 interventional 의학 사용 X-레이 안내에서 수행 Endovascular 절차 - 5. 반면 미디어의 사용을 통해 vasculature을 통해 탐색은의 내정 간섭 손 6 카테터 및 기계적 발전의 수동 회전을 통해 달성된다. 그러나 많은 혈관 구부러 주변의 작은 고통스러운 혈관을 통해 탐색은 대상 사이트에 도달하기 전에 시간을 elongating, 점점 더 어려워진다. 여기에는 occluded 혈관에 응고의 제거와 같은 시간에 민감한 절차에 대한 문제를 포즈. 또한, 장시간 절차는 방사선 복용량을 증가시키고 불리한 이벤트 7-11의 가능성을 만들 수 있습니다. 그러나, endovascular 절차 magneti에서 수행C 공명 영상이 해결책을 제공 할 수 있습니다. MRI 스캐너의 강한 균일 한 자기장은 원격 제어 12,13가 카테 테르 팁 탐색을 위해 악용 할 수 있습니다. 카테 테르 팁에 위치한 microcoil에 적용 현재는 MRI 스캐너 13 일 (그림 1)의 구멍과 정렬로 토크를 발생 작은 자기 모멘트를 유도한다. 전기 전류가 개인 코일이 활성화되어있는 경우, 카테 테르 팁은 원격 제어하여 한면에 편향 될 수 있습니다. 카테 테르 팁 세 코일이 활력 경우, 카테 테르 팁 편향은 3 차원으로 달성 될 수있다. 따라서, 카테 테르의 자기 (磁 气) 촉진 방향타가 절차 시간을 줄이고 환자 결과를 향상시킬 수 endovascular 절차에 혈관 탐색의 속도와 효능을 높일 수있는 가능성이 있습니다. microcoil - 스쳐 endovascular 카테터에 적용 전류 신뢰성과 제어 deflecti를 생성 할 수있는 경우 본 연구에서는, 우리는 검사카테 테르 탐색 연구에 대한 예비 테스트와 같은 MR-지도 아래 기능.

<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>
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 <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

X-레이 fluoroscopy - 가이드 endovascular 절차가 어려운 카테 테르 탐색 및 잠재적 MR지도 아래 자기 (磁 气) steerable 카테터를 사용하여 극복 할 수 이온화 방사선의 사용을 포함하여 몇 가지 중요한 제한이 있습니다. 이 작품의 주요 목표는 누구의 팁 원격 MR 스캐너의 자기장을 사용하여 제어 할 수 있습니다 microcatheter을 개발하는 것입니다. 이 프로토콜은 일관성과 제어 편향를 생성 할 microcoil - 스쳐 microcatheter에 현재 적용하기위한 절차를 설명하는 것을 목표로하고 있습니다. microcoil는 폴리이 미드 - 스쳐 endovascular 카테터에 레이저 선반 리소그래피를 사용하여 제조되었습니다. 체외 검사에서 정상 상태 무료 전진 (SSFP) 시퀀싱을 사용하여 1.5-T MR 시스템의지도하에 waterbath 및 선박 점선으로 수행되었다. 현재 다양한 금액은 MEA를 생성 할 microcatheter의 코일에 적용되었습니다sureable 팁 편향과 혈관 유령에 이동합니다. 이 장치의 개발은 향후 테스트 및 endovascular interventional MRI 환경을 혁명 기회를위한 플랫폼을 제공합니다.

0과 90도 사이의 처짐의 프로토콜 위에서 설명한에서 각도가 결합 된 솔레노이드와 Helmholtz 코일 microcatheter 시스템 (그림 2E)의 두 코일로 동시에 전달 전류의 50~3백mA의 응용 프로그램에서 관찰해야합니다. 양의 전류를 관찰 현재의 극성에 반전은 정반대 방향으로 편향가 될 동안 적용 전류의 증가는, microcatheter 편향 각도의 증가가 발생합니다 (그림 5A-5C). 편향의 각도는하?...

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

레이저 선반 리소그래피에 의한 microcoil 팁과 endovascular microcatheter에 적용 현재는 다양한 endovascular 절차 중 vasculature의 탐색 속도와 효능을 향상시킬 수 있습니다 자기 공명 (MR)지도, 아래 제어 편향를 얻을 수 있습니다.

자기 공명 영상 아래에 자기 (磁 气)를 이용한 원격 제어 Microcatheter 팁 편향

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

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12.3K 조회수.  University of California, San Francisco. 레이저 선반 리소그래피에 의한 microcoil 팁과 endovascular microcatheter에 적용 현재는 다양한 endovascular 절차 중 vasculature의 탐색 속도와 효능을 향상시킬 수 있습니다 자기 공명 (MR)지도, 아래 제어 편향를 얻을 수 있습니다.

비디오: 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).

조직 평가에 대한 자기 공명 Elastography 방법론은 구조 성장하는 기술

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

연구

생체공학

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.

에 대한 마이크로 미터 프로브의 원격 자기 발동<em&gt; 현장에서</em세균 바이오 필름 물성&gt; 3D 매핑

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.

자기 공명 이미지 지침에 열성 리포좀에서 시스플라틴의 트리거 된 릴리스를위한 맞춤 설계 레이저 기반의 가열 장치

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.

제어 약물 릴리스에 대한 자기장 응답 하이브리드 젤라틴 마이크로 겔을 교류

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.

빠른 스캔 전자 스핀 공명 이미징 생리 학적으로 중요 매개 변수에 대한 새로운 길을 엽니 다<em&gt; 생체</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.

질병 진단을위한 휴대용 이미징 및 분석과 결합 자기 부상

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.

자기 및 열에 민감한 폴리 (<em&gt; N</em&gt; - 이소 프로필 아크릴 아미드) 기반의 마그네틱 트리거 리간드 용 젤

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.

대사 지원 Excised, 자기 공명 현미경 중 생활 뇌 조직

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.

과분극[1-13C] 피루바테의 스핀 격자 이완 자기장 의존도 측정

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.

일축 인장 스트레인 하에서 살아있는 세포의 핵 역학에 대 한 고해상도 이미징

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

자기 공명 영상 아래에 자기 (磁 气)를 이용한 원격 제어 Microcatheter 팁 편향

자기 공명 영상 아래에 자기 (磁气)를 이용한 원격 제어 Microcatheter 팁 편향