وأيد هذا العمل من قبل منحة ويلكوم ترست 088419 إلى MDB ورعايته من قبل سميث ونفيو المحدودة في المملكة المتحدة

<ol>
	<li>Bass, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+syndecan-4+hair+trigger+initiates+wound+healing+through+caveolin-+and+RhoG-regulated+integrin+endocytosis.">A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis.</a> Dev. Cell. 21, 681-693 (2011).</li><li>Echtermeyer, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Delayed+wound+repair+and+impaired+angiogenesis+in+mice+lacking+syndecan-4.">Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4.</a> J. Clin. Invest. 107, R9-R14 (2001).</li><li>Bass, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Syndecan-4-dependent+Rac1+regulation+determines+directional+migration+in+response+to+the+extracellular+matrix.">Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix.</a> J. Cell Biol. 177, 527-538 (2007).</li><li>Woods, A., Couchman, J. R., Johansson, S., Hook, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adhesion+and+cytoskeletal+organisation+of+fibroblasts+in+response+to+fibronectin+fragments.">Adhesion and cytoskeletal organisation of fibroblasts in response to fibronectin fragments.</a> Embo. J. 5, 665-670 (1986).</li><li>Mahoney, C. M., Morgan, M. R., Harrison, A., Humphries, M. J., Bass, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Therapeutic+ultrasound+bypasses+canonical+syndecan-4+signaling+to+activate+rac1.">Therapeutic ultrasound bypasses canonical syndecan-4 signaling to activate rac1.</a> J. Biol. Chem. 284, 8898-8909 (2009).</li><li>Claes, L., Willie, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+enhancement+of+bone+regeneration+by+ultrasound.">The enhancement of bone regeneration by ultrasound.</a> Prog. Biophys. Mol. Biol. 93, 384-398 (2007).</li><li>Heckman, J. D., Ryaby, J. P., McCabe, J., Frey, J. J., Kilcoyne, R. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acceleration+of+tibial+fracture-healing+by+non-invasive,+low-intensity+pulsed+ultrasound.">Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound.</a> J. Bone Joint Surg. Am. 76, 26-34 (1994).</li><li>Kristiansen, T. K., Ryaby, J. P., McCabe, J., Frey, J. J., Roe, L. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Accelerated+healing+of+distal+radial+fractures+with+the+use+of+specific,+low-intensity+ultrasound.+A+multicenter,+prospective,+randomized,+double-blind,+placebo-controlled+study.">Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study.</a> J. Bone Joint Surg. Am. 79, 961-973 (1997).</li><li>Danen, E. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Requirement+for+the+synergy+site+for+cell+adhesion+to+fibronectin+depends+on+the+activation+state+of+integrin+alpha+5+beta+1.">Requirement for the synergy site for cell adhesion to fibronectin depends on the activation state of integrin alpha 5 beta 1.</a> J. Biol. Chem. 270, 21612-21618 (1995).</li><li>Del Pozo, M. A., Price, L. S., Alderson, N. B., Ren, X. D., Schwartz, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adhesion+to+the+extracellular+matrix+regulates+the+coupling+of+the+small+GTPase+Rac+to+its+effector+PAK.">Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK.</a> Embo. J. 19, 2008-2014 (2000).</li><li>Makarem, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Competitive+binding+of+vascular+cell+adhesion+molecule-1+and+the+HepII/IIICS+domain+of+fibronectin+to+the+integrin+alpha+4+beta+1.">Competitive binding of vascular cell adhesion molecule-1 and the HepII/IIICS domain of fibronectin to the integrin alpha 4 beta 1.</a> J. Biol. Chem. 269, 4005-4011 (1994).</li></ol>

أندرو هاريسون هو موظف في شركة سميث ونفيو المحدودة في المملكة المتحدة.

في هذا البروتوكول وصفنا الطريقة التي يمكن استخدامها لعلاج الذي يتم تطبيقه عادة للمرضى الإنسان في الخلية المستندة إلى التجارب. والهدف النهائي هو لفهم الآلية الجزيئية للعمل الموجات فوق الصوتية بحيث يمكن أن يتم تكريره في العلاج. في هذا البروتوكول، ونحن نستخدم الخلايا الليفية الماوس الجنينية (MEFs) كنموذج نظام الخلية، ولكن لم يتم العثور على الموجات فوق الصوتية أيضا أن تكون فعالة في الخلايا الليفية الأولية القلفة الإنسان 5، والخلايا الجذعية الوسيطة، وبانيات غضروفية 6. نحن نستخدم Rac1 تفعيل باعتباره فحص سبيل المثال الكيمياء الحيوية، ولكن يمكن استخدام أسلوب بالتساوي لاختبار تنظيم الفسفرة البروتين أو تشكيل مجمعات البروتين بواسطة مناعي. للمثال مناعي نظهر تأثير الموجات فوق الصوتية على تشكيل التصاق التنسيق، ولكن يمكن دراسة إعادة توزيع أي جزيء. على سبيل المثال، يمكن للمرء اختبار توظيف العوامل عصاري خلوي إلى غشاء البلازما، colocalisation من المتواجدالإضافية في الحويصلات الاتجار أو دراسة تأثير الموجات فوق الصوتية في منظمة مغزل الإنقسامية. حتى الآن لم يقتصر أنفسنا لاختبار فبرونيكتين التي تعتمد على المسارات، وذلك من تأثير الموجات فوق الصوتية على الخلايا على الكولاجين، أو في وجود عوامل النمو يمكن اختبار لبناء صورة لكيفية الموجات فوق الصوتية يؤثر على سلوك الخلية في بيئة معقدة أكثر يشبه وضعا في الجسم الحي. وسوف يكون أكبر تحد لاختبار تأثير الموجات فوق الصوتية باستخدام الوقت الفاصل بين التصوير، حيث وجود باعث عرقلة مسار الضوء والاهتزازات من العقبات الموجات فوق الصوتية الحالي فنية إضافية. ومع ذلك، فإن حقيقة أن تطبيق العلاج يتطلب 20 دقيقة فقط في اليوم الواحد من التحفيز يشير إلى أن تحليل سلوك الخلية بعد موجة من التحفيز قد تكون مثمرة.

<table border="1" style=";text-align:right;direction:rtl"><tbody><tr><td> اسم كاشف </td><td> شركة </td><td> فهرس العدد </td><td> تعليق (اختياري) </td></tr><tr><td> sulpho-M-maleimidobenzoyl-N-hydrosuccinimide استر </td><td> FisherPerbio </td><td> PN22312 </td><td> ويمكن تخزين 25 سهما ملي المذاب في الماء عند درجة حرارة -20 درجة مئوية </td></tr><tr><td> 6 كذلك لوحة زراعة الأنسجة </td><td> كورنينج </td><td> 3516 </td><td> ويمكن من البلاستيك من الشركات الأخرى معطف سيئة </td></tr><tr><td> 13 ملم الزجاج ساترة </td><td> مختبر علمي لوازم Ltd.SLS </td><td> MIC3336 </td><td> يمكن للزجاج من الشركات الأخرى معطف سيئة </td></tr><tr><td> برنامج تلفزيوني </td><td> سيغما </td><td> D8537 </td><td></td></tr><tr><td> برنامج تلفزيوني، كا 2 + 2 ملغ + </td><td> سيغما </td><td> D8662 </td><td></td></tr><tr><td> 50K إنتغرين يجند (شظية فبرونيكتين) </td><td> بناء وصف وقبلparation في 11 و 9 </td><td></td><td> ويمكن استخدام بديل يغاندس مصفوفة لاستجواب مسارات أخرى </td></tr><tr><td> جيش صرب البوسنة </td><td> سيغما </td><td> A3059 </td><td></td></tr><tr><td> سيكلوهيكسيميد </td><td> سيغما </td><td> C7698 </td><td> ويمكن تخزين الأوراق المالية كما 10mg/ml في الماء </td></tr><tr><td> DMEM/25 HEPES ملي </td><td> سيغما </td><td> D6171 </td><td></td></tr><tr><td> Exogen 4000 + </td><td> شركة سميث اند نفيو </td><td></td><td></td></tr><tr><td> الموجات فوق الصوتية اقتران هلام </td><td> شركة سميث اند نفيو </td><td></td><td></td></tr><tr><td> SAFHS مؤشر </td><td> شركة سميث اند نفيو </td><td></td><td></td></tr><tr><td> hVIN-1 </td><td> سيغما </td><td> V9264 </td><td></td></tr><tr><td> DyLight 488-مترافق مكافحة فأر </td><td> Stratech العلمية </td><td> 715-485-150 </td><td></td></tr><tr><td> TRITC ذات العلامات phalloidin &lt;/ TD&gt; <td> سيغما </td><td> P1951 </td><td></td></tr><tr><td> إطالة الذهب كاشف antifade </td><td> إينفيتروجن </td><td> P36930 </td><td></td></tr><tr><td> كاملة المانع البروتيني (EDTA الحرة) </td><td> روش </td><td> 056 489 001 </td><td> 100 × الأوراق المالية تتكون من قرص تخزين في -20 درجة مئوية </td></tr><tr><td> PAK-الجلوتاثيون الخرز الاغاروز </td><td> بناء وإعداد وصف في 10 </td><td></td><td></td></tr><tr><td> الغليسيرول </td><td> الصياد </td><td> G/0650/17 </td><td></td></tr><tr><td> Hepes </td><td> أبولو العلمية </td><td> BI8181 </td><td> جعل الأسهم 1M ودرجة الحموضة إلى 7.4 </td></tr><tr><td> كلوريد الصوديوم </td><td> الصياد </td><td> S/0160/65 </td><td></td></tr><tr><td> NP40 </td><td> سيغما </td><td> I3021 </td><td></td></tr><tr><td> الصوديوم Deoxycholate </td><td> سيغما </td><td> D6750 </td><td></td></tr><tr><td> EGTA </td><td> سيغما </td><td> E4378 </td><tد&gt; </td></tr><tr><td> EDTA </td><td> سيغما </td><td> E5134 </td><td></td></tr></tbody></table>

induction of adhesion-dependent signals using low-intensity ultrasound

في الكائنات متعددة الخلايا، وتملي سلوك الخلية عن طريق التفاعل مع المصفوفة خارج الخلية. نتائج مصفوفة الارتباط مجموعة من تنظيم الهجرة الخلية، وانتشار الأسلحة النووية، إلى إفراز وحتى التفريق. الإشارات الكامنة وراء كل من هذه العمليات المعقدة تنشأ من التفاعلات الجزيئية من مستقبلات المصفوفة خارج الخلية على سطح الخلية. integrins يست المستقبلات prototypic وتقديم وصلة ميكانيكية بين المصفوفة خارج الخلية والهيكل الخلوي، وكذلك الشروع في بعض من أجهزة الطرد المركزي التي تعتمد على الالتصاق مما يشير. ومع ذلك، فإنه بات من الواضح بشكل متزايد أن مستقبلات عبر الغشاء إضافية تعمل جنبا إلى جنب مع لل integrins لتنظيم كل من إنتغرين نفسها وإشارات المصب. وأكثر أناقة من هذه الأمثلة هو بروتيوغليكان عبر الغشاء، syndecan-4، والتي تتعاون مع β α 5 1-إنتغرين خلال التصاق إلى فبرونيكتين. في النماذج الحية demonstrأكلت على أهمية إشارات-4 syndecan، كما syndecan-4-خروج المغلوب الفئران تبدي تخلف الشفاء بسبب عدم كفاءة الخلايا الليفية 1،2 الهجرة. في البرية من نوع الحيوانات، ويتم تشغيل الهجرة من الخلايا الليفية نحو الجرح من قبل ظهور فبرونيكتين أن يترسب تتسرب من الشعيرات الدموية التالفة والتي الضامة في النسيج المصاب. ولذلك هناك اهتمام كبير في اكتشاف الاستراتيجيات التي تعزز فبرونيكتين التي تعتمد على الإشارات، ويمكن تسريع عمليات الإصلاح. ويمكن فصل مكونات إنتغرين بوساطة وsyndecan-4-بوساطة من فبرونيكتين التي تعتمد على إشارات من الخلايا المحفزة مع شظايا فبرونيكتين المؤتلف. على الرغم من أن إنتغرين المشاركة أمر ضروري للالتصاق الخلية، وينظم بعض فبرونيكتين التي تعتمد على الاشارات التي syndecan-4. Syndecan-4 ينشط إشارة Rac1 تبارزي 3، يسبب إنتغرين إعادة توزيع 1، مشغلات تجنيد جزيئات هيكل الخلية، مثل vinculin، إلى التنسيقالتصاقات 4، ويدفع بذلك الاتجاه 3 هجرة. كنا نبحث عن استراتيجيات بديلة لتفعيل مثل هذه الاشارات، ووجدت أن الموجات فوق الصوتية المنخفضة الحدة نابض (LIPUS) يمكن أن تحاكي آثار الاشتباك-4 syndecan 5. في هذا البروتوكول وصفنا الطريقة التي يمكن تطبيقها على 30 ميغاواط / سم 2، 1.5 ميغاهيرتز الموجات فوق الصوتية، نابض في 1 كيلو هرتز (الشكل 1) إلى الخلايا الليفية في ثقافة (الشكل 2) للحث على Rac1 التنشيط والتنسيق تشكيل الالتصاق. يتم تطبيق التحفيز الموجات فوق الصوتية لمدة أقصاها 20 دقيقة، كما تم العثور على هذه المجموعة من المعلمات لتكون الأكثر فعالية لتسريع اصلاح كسر السريرية 6. ويستخدم أسلوب شظايا فبرونيكتين المؤتلف للانخراط α β 5 1-إنتغرين، دون إشراك syndecan-4، ويتطلب تثبيط تخليق البروتين بواسطة سيكلوهيكسيميد لمنع ترسب مصفوفة إضافية من الخلايا الليفية.، وتأثير إيجابي سموثق بشكل جيد و الموجات فوق الصوتية على آليات إصلاح 7،8، و من خلال فهم تأثير الجزيئية الموجات فوق الصوتية في الثقافة يجب أن نكون قادرين على صقل هذه التقنية العلاجية لتحسين النتائج السريرية.

Watch this Scientific Journal Video about Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound at JoVE.com

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound

يصف هذا بروتوكول تحفيز الخلايا الليفية مثقف مع الموجات فوق الصوتية المنخفضة الحدة نابض، وهو ما يدفع التنسيق تشكيل التصاق وRac1 تفعيل عن طريق محاكاة إشراك عبر الغشاء مستقبلات مصفوفة، syndecan-4. ويسمح هذا النهج من التحقيق تقنية السريرية ناجح على المستوى الخلوي، وبالتالي توفير فرص للتحسين من العلاج.

تحريض الإشارات التصاق التي تعتمد على استخدام الموجات فوق الصوتية المنخفضة الحدة

In multicellular organisms, cell behavior is dictated by interactions with the extracellular matrix. Consequences of matrix-engagement range from ...

induction-of-adhesion-dependent-signals-using-low-intensity-ultrasound

Research

JoVE Journal

Bioengineering

9.4K Views.  University of Bristol. يصف هذا بروتوكول تحفيز الخلايا الليفية مثقف مع الموجات فوق الصوتية المنخفضة الحدة نابض، وهو ما يدفع التنسيق تشكيل التصاق وRac1 تفعيل عن طريق محاكاة إشراك عبر الغشاء مستقبلات مصفوفة، syndecan-4. ويسمح هذا النهج من التحقيق تقنية السريرية ناجح على المستوى الخلوي، وبالت?...

Video: Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters.  Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation.  Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Insonation of microbubbles is a promising strategy for tumor ablation at reduced time-averaged acoustic powers, as well as for the targeted delivery of therapeutics. The purpose of the present study is to develop low duty cycle ultrasound pulsing strategies and nanocarriers to maximize non-thermal microvascular ablation and payload delivery to subcutaneous C6 gliomas.

الموجات فوق الصوتية على النقيض المستهدفة علاج الاورام الدبقية في الفئران عن طريق تسليم المخدرات جسيمات متناهية الصغر ، إذ تضع وتذرية الاوعية الدموية الدقيقة

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the ...

Introduction to the Ultrasound Targeted Microbubble Destruction Technique

In UTMD, bioactive molecules, such as negatively charged plasmid DNA vectors encoding a gene of interest, are added to the cationic shells of lipid microbubble contrast agents7-9. In mice these vector-carrying microbubbles can be administered intravenously or directly to the left ventricle of the heart. In larger animals they can also be infused through an intracoronary catheter. The subsequent delivery from the circulation to a target organ occurs by acoustic cavitation at a resonant frequency of the microbubbles. It seems likely that the mechanical energy generated by the microbubble destruction results in transient pore formation in or between the endothelial cells of the microvasculature of the targeted region10. As a result of this sonoporation effect, the transfection efficiency into and across the endothelial cells is enhanced, and transgene-encoding vectors are deposited into the surrounding tissue. Plasmid DNA remaining in the circulation is rapidly degraded by nucleases in the blood, which further reduces the likelihood of delivery to non-sonicated tissues and leads to highly specific target-organ transfection.

Ultrasound Targeted Microbubble Destruction (UTMD) can be used to direct site-specific delivery of bioactive molecules, including therapeutic genes, to target organs accessible to ultrasound, such as the heart and liver1-6.

مقدمة لتقنية الموجات فوق الصوتية مستهدفة تدمير Microbubble

In UTMD, bioactive molecules, such as negatively charged plasmid DNA vectors encoding a gene of interest, are added to the cationic shells of lipid ...

Wideband Optical Detector of Ultrasound for Medical Imaging Applications

Optical sensors of ultrasound are a promising alternative to piezoelectric techniques, as has been recently demonstrated in the field of optoacoustic imaging. In medical applications, one of the major limitations of optical sensing technology is its susceptibility to environmental conditions, e.g. changes in pressure and temperature, which may saturate the detection. Additionally, the clinical environment often imposes stringent limits on the size and robustness of the sensor. In this work, the combination of pulse interferometry and fiber-based optical sensing is demonstrated for ultrasound detection. Pulse interferometry enables robust performance of the readout system in the presence of rapid variations in the environmental conditions, whereas the use of all-fiber technology leads to a mechanically flexible sensing element compatible with highly demanding medical applications such as intravascular imaging. In order to achieve a short sensor length, a pi-phase-shifted fiber Bragg grating is used, which acts as a resonator trapping light over an effective length of 350 &#181;m. To enable high bandwidth, the sensor is used for sideway detection of ultrasound, which is highly beneficial in circumferential imaging geometries such as intravascular imaging. An optoacoustic imaging setup is used to determine the response of the sensor for acoustic point sources at different positions.

Optical detection of ultrasound is impractical in many imaging scenarios because it often requires stable environmental conditions. We demonstrate an optical technique for ultrasound sensing in volatile environments with miniaturization and sensitivity levels appropriate for optoacoustic imaging in restrictive scenarios, e.g. intravascular applications.

النطاق العريض للكشف عن الموجات فوق الصوتية البصرية للتطبيقات التصوير الطبي

Optical sensors of ultrasound are a promising alternative to piezoelectric techniques, as has been recently demonstrated in the field of optoacoustic ...

Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU)

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An oscillatory motion is generated at the focus of a 93-element and 4.5 MHz center frequency HIFU transducer by applying a 25 Hz amplitude-modulated signal using a function generator. A 64-element and 2.5 MHz imaging transducer with 68kPa peak pressure is confocally placed at the center of the HIFU transducer to acquire the radio-frequency (RF) channel data. In this protocol, real-time monitoring of thermal ablation using HIFU with an acoustic power of 7 W on canine livers in vitro is described. HIFU treatment is applied on the tissue during 2 min and the ablated region is imaged in real-time using diverging or plane wave imaging up to 1,000 frames/second. The matrix of RF channel data is multiplied by a sparse matrix for image reconstruction. The reconstructed field of view is of 90&#176; for diverging wave and 20 mm for plane wave imaging and the data are sampled at 80 MHz. The reconstruction is performed on a Graphical Processing Unit (GPU) in order to image in real-time at a 4.5 display frame rate. 1-D normalized cross-correlation of the reconstructed RF data is used to estimate axial displacements in the focal region. The magnitude of the peak-to-peak displacement at the focal depth decreases during the thermal ablation which denotes stiffening of the tissue due to the formation of a lesion. The displacement signal-to-noise ratio (SNRd) at the focal area for plane wave was 1.4 times higher than for diverging wave showing that plane wave imaging appears to produce better displacement maps quality for HMIFU than diverging wave imaging.

Real-time Monitoring of High Intensity Focused Ultrasound HIFU Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound HMIFU

This article describes real-time monitoring of HIFU ablation in canine liver with high frame rate ultrasound imaging using diverging and plane wave imaging. Harmonic Motion Imaging for Focused Ultrasound is used to image the decrease of acoustic radiation force induced displacement in the ablated region.

رصد في الوقت الحقيقي وارتفاع كثافة الموجات فوق الصوتية المركزة (HIFU) تذرية<em&gt; في المختبر</em&gt; الناب الأكباد عن طريق متناسق الحركة التصوير بالموجات فوق الصوتية المركزة ل(HMIFU)

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An ...

Transmission of Multiple Signals through an Optical Fiber Using Wavefront Shaping

The transmission of multiple independent optical signals through a multimode fiber is accomplished using wavefront shaping in order to compensate for the light distortion during the propagation within the fiber. Our methodology is based on digital optical phase conjugation employing only a single spatial light modulator, where the optical wavefront is individually modulated at different regions of the modulator, one region per light signal. Digital optical phase conjugation approaches are considered to be faster than other wavefront shaping approaches, where (for example) a complete determination of the wave propagation behavior of the fiber is performed. In contrast, the presented approach is time-efficient since it only requires one calibration per light signal. The proposed method is potentially appropriate for spatial division multiplexing in communications engineering. Further application fields are endoscopic light delivery in biophotonics, especially in optogenetics, where single cells in biological tissue have to be selectively illuminated with high spatial and temporal resolution.

We demonstrate the transmission of multiple independent signals through a multimode fiber using wavefront shaping employing a single spatial light modulator. By modulating the wavefront for each signal individually, spatially separated foci are transmitted. Potential applications are multiplexed data transfer in communications engineering and endoscopic light delivery in biophotonics.

انتقال إشارات متعددة من خلال الألياف البصرية عن طريق واجهة الموجة تشكيل

The transmission of multiple independent optical signals through a multimode fiber is accomplished using wavefront shaping in order to compensate for the ...

Manufacturing Abdominal Aorta Hydrogel Tissue-Mimicking Phantoms for Ultrasound Elastography Validation

Ultrasound (US) elastography, or elasticity imaging, is an adjunct imaging technique that utilizes sequential US images of soft tissues to measure the tissue motion and infer or quantify the underlying biomechanical characteristics. For abdominal aortic aneurysms (AAA), biomechanical properties such as changes in the tissue's elastic modulus and estimates of the tissue stress may be essential for assessing the need for the surgical intervention. Abdominal aortic aneurysms US elastography could be a useful tool to monitor AAA progression and identify changes in biomechanical properties characteristic of high-risk patients.
A preliminary goal in the development of an AAA US elastography technique is the validation of the method using a physically relevant model with known material properties. Here we present a process for the production of AAA tissue-mimicking phantoms with physically relevant geometries and spatially modulated material properties. These tissue phantoms aim to mimic the US properties, material modulus, and geometry of the abdominal aortic aneurysms. Tissue phantoms are made using a polyvinyl alcohol cryogel (PVA-c) and molded using 3D printed parts created using computer aided design (CAD) software. The modulus of the phantoms is controlled by altering the concentration of PVA-c and by changing the number of freeze-thaw cycles used to polymerize the cryogel. The AAA phantoms are connected to a hemodynamic pump, designed to deform the phantoms with the physiologic cyclic pressure and flows. Ultra sound image sequences of the deforming phantoms allowed for the spatial calculation of the pressure normalized strain and the identification of mechanical properties of the vessel wall. Representative results of the pressure normalized strain are presented.

Here we describe a method to manufacture aneurysmal, aortic tissue-mimicking phantoms for the use in testing ultrasound elastography. The combined use of computer-aided design (CAD) and 3-dimensional (3D) printing techniques produce aortic phantoms with predictable, complex geometries to validate the elastographic imaging algorithms with controlled experiments.

تصنيع الشريان الاورطي البطني المائية الأنسجة محاكاة أشباح للتحقق من صحة الاستوجرافي بالموجات فوق الصوتية

Ultrasound (US) elastography, or elasticity imaging, is an adjunct imaging technique that utilizes sequential US images of soft tissues to measure the ...

Functional Transcranial Doppler Ultrasound for Monitoring Cerebral Blood Flow

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli such as physical movement, activation of tactile sensors in the skin, and viewing images. Neural activation is inferred from an increase in the cerebral blood flow velocity (CBFV) supplying the region of the brain involved in processing sensory input. For example, viewing bright light causes increased neural activity in the occipital lobe of the cerebral cortex, leading to increased blood flow in the posterior cerebral artery, which supplies the occipital lobe. In fTCD, changes in CBFV are used to estimate changes in cerebral blood flow (CBF).
With its high temporal resolution measurement of blood flow velocities in the major cerebral arteries, fTCD complements other established functional imaging techniques. The goal of this Methods paper is to give step-by-step instructions for using fTCD to perform a functional imaging experiment. First, the basic steps for identifying the middle cerebral artery (MCA) and optimizing the signal will be described. Next, placement of a fixation device for holding the TCD probe in place during the experiment will be described. Finally, the breath-holding experiment, which is a specific example of a functional imaging experiment using fTCD, will be demonstrated.

Functional transcranial Doppler ultrasound complements other functional imaging modalities, with its high temporal resolution measurement of stimulus-induced changes in cerebral blood flow within the basal cerebral arteries. This Methods paper gives step-by-step instructions for using functional transcranial Doppler ultrasound to perform a functional imaging experiment.&#160;

وظيفية عبر الجمجمة دوبلر الموجات فوق الصوتية لرصد تدفق الدم الدماغي

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli ...

Contrast-Enhanced Subharmonic Aided Pressure Estimation (SHAPE) Using Ultrasound Imaging with a Focus on Identifying Portal Hypertension

Noninvasive, accurate measurement of pressures within the human body has long been an important but elusive clinical goal. Contrast agents for ultrasound imaging are gas-filled, encapsulated microbubbles (diameter &#60; 10 &#956;m) that traverse the entire vasculature and enhance signals by up to 30 dB. These microbubbles also produce nonlinear oscillations at frequencies ranging from the subharmonic (half of the transmit frequency) to higher harmonics. The subharmonic amplitude has an inverse linear relationship with the ambient hydrostatic pressure. Here an ultrasound system capable of performing real-time, subharmonic aided pressure estimation (SHAPE) is presented. During ultrasound contrast agent infusion, an algorithm for optimizing acoustic outputs is activated. Following this calibration, subharmonic microbubble signals (i.e., SHAPE) have the highest sensitivity to pressure changes and can be used to noninvasively quantify pressure. The utility of the SHAPE procedure for identifying portal hypertension in the liver is the emphasis here, but the technique has applicability across many clinical scenarios.

Contrast-Enhanced Subharmonic Aided Pressure Estimation SHAPE Using Ultrasound Imaging with a Focus on Identifying Portal Hypertension

A protocol for noninvasively estimating ambient pressures utilizing subharmonic ultrasound imaging of infused contrast microbubbles (following appropriate calibration) is described with examples from human patients with chronic liver disease.

تقدير الضغط بمساعدة دون التوافقي المعزز بالتباين (SHAPE) باستخدام التصوير بالموجات فوق الصوتية مع التركيز على تحديد ارتفاع ضغط الدم البابي

Noninvasive, accurate measurement of pressures within the human body has long been an important but elusive clinical goal. Contrast agents for ultrasound ...

Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release

Microbubble contrast agents hold great promise for drug delivery applications with ultrasound. Encapsulating drugs in nanoparticles reduces systemic toxicity and increases circulation time of the drugs. In a novel approach to microbubble-assisted drug delivery, nanoparticles are incorporated in or on microbubble shells, enabling local and triggered release of the nanoparticle payload with ultrasound. A thorough understanding of the release mechanisms within the vast ultrasound parameter space is crucial for efficient and controlled release. This set of presented protocols is applicable to microbubbles with a shell containing a fluorescent label. Here, the focus is on microbubbles loaded with poly(2-ethyl-butyl cyanoacrylate) polymeric nanoparticles, doped with a modified Nile Red dye. The particles are fixed within a denatured casein shell. The microbubbles are produced by vigorous stirring, forming a dispersion of perfluoropropane gas in the liquid phase containing casein and nanoparticles, after which the microbubble shell self-assembles. A variety of microscopy techniques are needed to characterize the nanoparticle-stabilized microbubbles at all relevant timescales of the nanoparticle release process. Fluorescence of the nanoparticles enables confocal imaging of single microbubbles, revealing the particle distribution within the shell. In vitro ultra-high-speed imaging using bright-field microscopy at 10 million frames per second provides insight into the bubble dynamics in response to ultrasound insonation. Finally, nanoparticle release from the bubble shell is best visualized by means of fluorescence microscopy, performed at 500,000 frames per second. To characterize drug delivery in vivo, the triggered release of nanoparticles within the vasculature and their extravasation beyond the endothelial layer is studied using intravital microscopy in tumors implanted in dorsal skinfold window chambers, over a timescale of several minutes. The combination of these complementary characterization techniques provides unique insight into the behavior of microbubbles and their payload release at a range of time and length scales, both in vitro and in vivo.

The presented protocols can be used to characterize the response of fluorescently-labeled microbubbles designed for ultrasound-triggered drug delivery applications, including their activation mechanisms as well as their bioeffects. This paper covers a range of in vitro and in vivo microscopy techniques performed to capture the relevant length and timescales.

طرق المجهر متعددة الوقت لتوصيف الفقاعات الدقيقة ذات العلامات الفلورية لإطلاق المخدرات التي تسببها الموجات فوق الصوتية

Microbubble contrast agents hold great promise for drug delivery applications with ultrasound. Encapsulating drugs in nanoparticles reduces systemic ...

In vitro Induction of Human Dental Pulp Stem Cells Toward Pancreatic Lineages

As of 2000, the success of pancreatic islet transplantation using the Edmonton protocol to treat type I diabetes mellitus still faced some obstacles. These include the limited number of cadaveric pancreas donors and the long-term use of immunosuppressants. Mesenchymal stem cells (MSCs) have been considered to be a potential candidate as an alternative source of islet-like cell generation. Our previous reports have successfully illustrated the establishment of induction protocols for differentiating human dental pulp stem cells (hDPSCs) to insulin-producing cells (IPCs). However, the induction efficiency varied greatly. In this paper, we demonstrate the comparison of hDPSCs pancreatic induction efficiency via integrative (microenvironmental and genetic manipulation) and non-integrative (microenvironmental manipulation) induction protocols for delivering hDPSC-derived IPCs (hDPSC-IPCs). The results suggest distinct induction efficiency for both the induction approaches in terms of 3-dimensional colony structure, yield, pancreatic mRNA markers, and functional property upon multi-dosage glucose challenge. These findings will support the future establishment of a clinically applicable IPCs and pancreatic lineage production platform.

In vitro Induction of Human Dental Pulp Stem Cells Toward Pancreatic Lineages

This protocol presents a comparison between two different induction protocols for differentiating human dental pulp stem cells (hDPSCs) toward pancreatic lineages in vitro: the integrative protocol and the non-integrative protocol. The integrative protocol generates more insulin producing cells (IPCs).

في المختبر تحريض الخلايا الجذعية لب الأسنان البشري نحو أنساب البنكرياس

As of 2000, the success of pancreatic islet transplantation using the Edmonton protocol to treat type I diabetes mellitus still faced some obstacles. ...