Yazarlar Semmes-Murphey Kliniği, Memphis, Tennessee yanı sıra Memphis Tennessee Sağlık Bilimleri Merkezi Üniversitesi&#39;nde, Tennessee Nöroşirürji bölümünde MR tesislerden personel teşekkür etmek istiyorum.

1.. Jel Hayaletleri hazırlanması ve Boya <ol><li> Iyonu giderilmiş su 1000 ml% 0.1 &#39;lik agaroz tozun 2 g eritilerek% 0.2 agaroz jeli hazırlayın. Uygun karışmasını sağlamak için yaklaşık olarak 1 dakika boyunca çözelti karıştırılır; ve hemen aralarda karıştırarak, 9 dakika için 3 dakika aralıklarla veya temizlenene kadar çözelti mikrodalga. </li><li> Agaroz jel, sıvı iken, 5 cm x 5 cm x 5 cm kaplara solüsyonu dökün. Su ekleyin ve agaroz jel serin ve yerleşmesine izin üzere kabın üst kısmında yer bırakın. </li><li> Agaroz jel (yaklaşık 1-2 saat) bir kez katılaştınldıktan sonra jel ve buzdolabına üstüne suyun 1 cm ekleyin. Bu karışım 24-48 saat içinde jel kullanmak en iyisidir, ama bir hafta kadar buzdolabında 10 için saklanabilir. </li><li> % 0.017 bromofenol mavisi boya (BPB), 50 ml ve gadoteridol radyo kontrast 2 mM oluşan bir 60 ml şırınga içinde bir radyo kontrastlı boya hazırlayın. <ol><li> 50 m BPB boyasının 8.5 mg birleştirinl Bir 0.017% BPB çözümü oluşturmak için deiyonize su. </li><li> 2 mM gadoteridol çözüm oluşturmak için 50 ml% 0.017 BPB çözüm stokunun 0.2 ml 0.5 M gadoteridol ekleyin. </li></ol></li></ol> İnfüzyon 2 Sistemin. Hazırlanması <ol><li> Şırınga pompası infüzyon sistemi (tercih edilen yöntem): şırınga pompası hazırlanması için, infüzyon hattının ölü hacmini azaltır, basınç sensörü vasıtasıyla şırıngaya doğrudan enfüzyon kateterini ekleyin. Şırınga pompasının boşaltma işlevi, 10 ul / dk &#39;lık bir hızda, kateterin hazırlama hacminden daha büyük olan bir bolus ile bir hava hattını temizlemek için kullanılabilir. </li><li> Boru pompa infüzyon sistemi (alternatif yöntem): infüzyon pompasına radyo-kontrast boya içeren şırınga bağlayın. IV monitöre bağlı transdüser ile pompa çıkışına basınç sensörü takın. Basınç sensörünün açık ucuna bir 16 G kateter infüzyon takın. Not: 16 G infüzyon kateterin ucu bir iç çapı vardır0.2 mm ve 0,35 mm arasında bir dış çapa sahip ölçer. Ucu erimiş silis yapılmış ve uç uzunluğu 3 mm olmasıdır. Bu, yaklaşık olarak 0.75 mm artar ve 15 mm boyunca devam eder, daha sonra kateter 1.6 mm ya da 16 G. konik bir şekilde artırdı </li><li> Herhangi bir hava kabarcıklarını çıkarmak için 16,667 ul / dk &#39;da, yaklaşık 15 dakika boyunca temizleme sistemi ile infüzyon için hazırlayın. Nedeniyle makine yüksek hat basınç infüzyon sona erecek gibi, 16.667 ul / dk akış hızı aşmayın. Infüzyon pompası, infüzyon pompası &quot;Bolus&quot; fonksiyonunu kullanarak hava boşaltma hatları çıkmadan hattına infüzyon kateteri takılarak ardından. </li><li> Infüzyon kateteri monte takın ve jel fantom kabın (5 cm x 5 cm x 5 cm) ve MRG yere yörünge çerçeve. </li></ol> 3.. CED Jel İnfüzyon ve MR Tarama <ol><li> Infüzyon başlamadan önce IV monitörü tarafından kaydedilen basınç değerini (mmHg) sıfır. </li><li> Agaroz jel w içine enfüzyon kateterini kaydedinITH infüzyon pompası bu durumda 1.667 ul / dk, mümkün olan en düşük akış hızında çalışıyor. </li><li> Tablo 1 &#39;de listelenen parametreler kullanılarak, MR tarama başlayın ve 1.667 ul / dk&#39; lık bir oranda infüzyonla devam etmektedir. Infüzyon toplam hacim 60 ul (yaklaşık 38 dakika) ulaşana kadar sabit bir hızda jel infüze. </li><li> 3 dakika ve 50 saniye aralıklarla sürekli olarak jel tarama. Basınç okumalarında her 60 sn kaydedin. Infüzyon hacmi 60 ul ulaştığında, infüzyon pompa kapatın; ve tam MR tarama basıncı okumaları kayıt devam ederken. </li></ol> 4. MR Veri Analizi <ol><li> MR görüntüleri analiz için, ROI segmentasyon işlevselliği ile uygun bir DICOM görüntüleyici kullanın. </li><li> Şekil 1 &#39;de görüldüğü gibi, kateterin enine kesit ile işaretlenmiştir tarama doğru çerçeveyi seçin. </li><li> &quot;ROI - dikdörtgen&quot; kullanarak aracı, herhangi bir içermez jelin büyük bölümünü seçininfüzyon sitenin bölümü. Yazılım irade çıktı standart sapma ile ortalama piksel yoğunluğu. Ortalama üç standart sapma karşılık gelen değeri bulun. Bu değer,% 99.7 bir kontrast bir güven ile mevcut olduğu zaman, belirlemek için bir eşik değeri olarak kullanılır. </li><li> &quot;ROI - daire&quot; kullanarak aracı, yeterince büyük bir daire ile infüzyon bölgesini çevreleyen ve bu benzersiz bir ad verin. </li><li> Daireyi seçin ve kullanarak &quot;ROI - ayarlamak piksel değerleri için&quot; aracı, içine adım 4.3 bulundu giriş eşik değer &quot;Geçerli değer daha büyük ise:&quot; kutusunda ve sadece bu satırı onay işareti. Sonra da &quot;Bu yeni değer:&quot; kutusunda, büyük bir değer (25.000) girin. Önceden tanımlanmış eşik kapsadığı alanı seçmek için piksel yoğunluğu sıfırlayın. </li><li> Sonra, &quot;ROI - bölgesini büyümek (2D/3D segmentasyon)&quot; kullanarak aracı, 2D büyüyen bölge, = 2 başlangıç ​​yarıçapı parametre ile güven algoritması ve fırça ROI seçin. Toplam alanı hesaplamak için yazılım için infüzyon sitenin içine tıklayın of bu bölge. </li><li> Küresel bir infüzyon bulut varsayarak, aşağıdaki denklem ile alanından yayılma hacmi hesaplanır: V = 4/3π (√ (Alanı / π)) 3 </li></ol>

<ol>
	<li>Miranpuri, G. S., 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=Gene-based+therapy+of+Parkinson's+Disease:+Translation+from+animal+model+to+human+clinical+trial+employing+convection+enhanced+delivery.">Gene-based therapy of Parkinson's Disease: Translation from animal model to human clinical trial employing convection enhanced delivery.</a> Annals of Neurosciences. 19, 133-146 (2012).</li><li>Sillay, K., Hinchman, A., Akture, E., Salamat, S., Miranpuri, G., Williams, J., Berndt, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection+Enhanced+Delivery+to+the+Brain:+Preparing+for+Gene+Therapy+and+Protein+Delivery+to+the+Brain+for+Functional+and+Restorative+Neurosurgery+by+Understanding+Low-Flow+Neurocatheter+Infusions+Using+the+Alaris&#174;+System+Infusion+Pump.">Convection Enhanced Delivery to the Brain: Preparing for Gene Therapy and Protein Delivery to the Brain for Functional and Restorative Neurosurgery by Understanding Low-Flow Neurocatheter Infusions Using the Alaris&#174; System Infusion Pump.</a> Annals of Neurosciences. 20, (2013).</li><li>Song, D. K., Lonser, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+for+the+treatment+of+pediatric+neurologic+disorders.">Convection-enhanced delivery for the treatment of pediatric neurologic disorders.</a> Journal of child neurology. 23, 1231-1237 (2008).</li><li>Bobo, R. 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=Convection-enhanced+delivery+of+macromolecules+in+the+brain.">Convection-enhanced delivery of macromolecules in the brain.</a> Proc Natl Acad Sci USA. 91, 2076-2080 (1994).</li><li>Debinski, W., Tatter, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+for+the+treatment+of+brain+tumors.">Convection-enhanced delivery for the treatment of brain tumors.</a> Expert review of neurotherapeutics. 9, 1519-1527 (2009).</li><li>Morrison, P. F., Laske, D. W., Bobo, H., Oldfield, E. H., Dedrick, 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=High-flow+microinfusion:+tissue+penetration+and+pharmacodynamics.">High-flow microinfusion: tissue penetration and pharmacodynamics.</a> The American journal of physiology. 266, 292-305 (1994).</li><li>Nguyen, T. T., 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=Convective+distribution+of+macromolecules+in+the+primate+brain+demonstrated+using+computerized+tomography+and+magnetic+resonance+imaging.">Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging.</a> Journal of neurosurgery. 98, 584-590 (2003).</li><li>Lonser, R. R., 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=Successful+and+safe+perfusion+of+the+primate+brainstem:+in+vivo+magnetic+resonance+imaging+of+macromolecular+distribution+during+infusion.">Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion.</a> Journal of neurosurgery. 97, 905-913 (2002).</li><li>Raghavan, R., 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=Convection-enhanced+delivery+of+therapeutics+for+brain+disease,+and+its+optimization.">Convection-enhanced delivery of therapeutics for brain disease, and its optimization.</a> Neurosurg Focus. 20, (2006).</li><li>Sillay, K., 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=Benchmarking+the+ERG+valve+tip+and+MRI+Interventions+Smart+Flow+neurocatheter+convection-enhanced+delivery+system's+performance+in+a+gel+model+of+the+brain:+employing+infusion+protocols+proposed+for+gene+therapy+for+Parkinson's+disease.">Benchmarking the ERG valve tip and MRI Interventions Smart Flow neurocatheter convection-enhanced delivery system's performance in a gel model of the brain: employing infusion protocols proposed for gene therapy for Parkinson's disease.</a> Journal of neural engineering. 9, (2012).</li><li>Schomberg, D., Wang, A., Marshall, H., Sillay, K., Miranpuri, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ramped-Rate+vs.+continuous+rate+infusions:+An+in+vitro+comparison+of+Convection+Enhanced+Delivery+protocols.">Ramped-Rate vs. continuous rate infusions: An in vitro comparison of Convection Enhanced Delivery protocols.</a> Annals of Neurosciences. 20, (2013).</li><li>Sillay, K. 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=Perioperative+Brain+Shift+and+Deep+Brain+Stimulating+Electrode+Deformation+Analysis:+Implications+for+rigid+and+non-rigid+devices.">Perioperative Brain Shift and Deep Brain Stimulating Electrode Deformation Analysis: Implications for rigid and non-rigid devices.</a> Ann Biomed Eng. 41, 293-304 (2013).</li><li>Brodsky, E., Block, W., Alexander, A., Emborg, M., Ross, C., Sillay, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+Device+Targeting+using+Real-Time+MRI.">Intraoperative Device Targeting using Real-Time MRI.</a> Biomedical Sciences and Engineering Conference, BSEC. , (2011).</li><li>Sillay, K., 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=Strategies+for+the+delivery+of+multiple+collinear+infusion+clouds+in+convection-enhanced+delivery+in+the+treatment+of+Parkinson's+disease.">Strategies for the delivery of multiple collinear infusion clouds in convection-enhanced delivery in the treatment of Parkinson's disease.</a> Stereotactic and functional neurosurgery. 91, 153-161 (2013).</li><li>Brady, M. 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=Pathways+of+infusate+loss+during+convection-enhanced+delivery+into+the+putamen+nucleus.">Pathways of infusate loss during convection-enhanced delivery into the putamen nucleus.</a> Stereotactic and functional neurosurgery. 91, 69-78 (2013).</li><li>White, E., 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=An+evaluation+of+the+relationships+between+catheter+design+and+tissue+mechanics+in+achieving+high-flow+convection-enhanced+delivery.">An evaluation of the relationships between catheter design and tissue mechanics in achieving high-flow convection-enhanced delivery.</a> J Neurosci Methods. 199, 87-97 (2011).</li><li>Fiandaca, M. S., Forsayeth, J. R., Dickinson, P. J., Bankiewicz, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+convection-enhanced+delivery+platform+in+the+treatment+of+neurological+diseases.">Image-guided convection-enhanced delivery platform in the treatment of neurological diseases.</a> Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 5, 123-127 (2008).</li><li>Jagannathan, J., Walbridge, S., Butman, J. A., Oldfield, E. H., Lonser, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+ependymal+and+pial+surfaces+on+convection-enhanced+delivery.">Effect of ependymal and pial surfaces on convection-enhanced delivery.</a> Journal of neurosurgery. 109, 547-552 (2008).</li><li>Chen, Z. J., Broaddus, W. C., Viswanathan, R. R., Raghavan, R., Gillies, G. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraparenchymal+drug+delivery+via+positive-pressure+infusion:+experimental+and+modeling+studies+of+poroelasticity+in+brain+phantom+gels.">Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels.</a> IEEE transactions on bio-medical engineering. 49, 85-96 (2002).</li><li>Chen, Z. 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=A+realistic+brain+tissue+phantom+for+intraparenchymal+infusion+studies.">A realistic brain tissue phantom for intraparenchymal infusion studies.</a> Journal of neurosurgery. 101, 314-322 (2004).</li><li>Richardson, R. M., 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=Interventional+MRI-guided+Putaminal+Delivery+of+AAV2-GDNF+for+a+Planned+Clinical+Trial+in+Parkinson's+Disease.">Interventional MRI-guided Putaminal Delivery of AAV2-GDNF for a Planned Clinical Trial in Parkinson's Disease.</a> Mol Ther. 19, 1048-1057 (2011).</li><li>Thorne, R. G., Hrabetova, S., Nicholson, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diffusion+of+epidermal+growth+factor+in+rat+brain+extracellular+space+measured+by+integrative+optical+imaging.">Diffusion of epidermal growth factor in rat brain extracellular space measured by integrative optical imaging.</a> Journal of neurophysiology. 92, 3471-3481 (2004).</li><li>Panse, S. J., Fillmore, H. L., Chen, Z. J., Gillies, G. T., Broaddus, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+coaxial+tube+catheter+for+central+nervous+system+infusions:+performance+characteristics+in+brain+phantom+gel.">A novel coaxial tube catheter for central nervous system infusions: performance characteristics in brain phantom gel.</a> J Med Eng Technol. 35, 408-414 (2010).</li><li>Linninger, A. A., Somayaji, M. R., Zhang, L., Smitha Hariharan, M., Penn, R. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rigorous+mathematical+modeling+techniques+for+optimal+delivery+of+macromolecules+to+the+brain.">Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain.</a> IEEE transactions on bio-medical engineering. 55, 2303-2313 (2008).</li><li>Sampson, J. 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=Clinical+utility+of+a+patient-specific+algorithm+for+simulating+intracerebral+drug+infusions.">Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.</a> Neuro-oncology. 9, 343-353 (2007).</li></ol>

Yazarlar, hiçbir rakip mali çıkarlarını olmadığını beyan ederim.

<html> Infüzyon başarısını sağlamak için kritik adımlar vardır: Havanın infüzyon hattını tasfiye agaroz jel karıştırma, MR verileri analiz, küçük iç kateter çapları kullanarak kullanarak akışını en aza indirmek için kateter tasarımlar çıktı ve tarafından hissedilen baskıyı minimize ilaç infüzyon edilmektedir jel ya da doku içine. Daha önce de belirtildiği gibi, infüzyon başarısı için en önemli zararlı infüzyon hattı havadır. Doğru ve iyice havanın infüzyon hattı temizl...

Konveksiyon geliştirilmiş dağıtım (CED) habis beyin tümörü, epilepsi, metabolik hastalıklar (örneğin, Parkinson hastalığı gibi) nörodejeneratif hastalıklar, 1, felç ve travma 2 de dahil olmak üzere nörolojik bozukluklar, geniş bir spektrum için bir tedavi seçeneği olarak önerilmiştir. CED bir ilaç veya başka infüzatı dağıtımı için pozitif basınçlı toplu akışını kullanır. CED klinik olarak önemli hacimlerde 3 at, düşük yüksek değişen, moleküler bileşiklerin, güvenli, güvenilir, ve homojen teslim sağlar. Beyin dokusu Geleneksel ilaç verme ciddi, kan-beyin bariyeri 4 ile sınırlıdır. Beyin parankimi girmesini kan-beyin bariyeri blok polar ve yüksek molekül ağırlıklı molekülleri, beyindeki kılcal oluşturan endotelyal hücreler arasındaki sıkı birleşme oluşturduğu. CED yoluyla doğrudan intraparenkimal beyin infüzyon önceki terapötik ilaç dağıtım yöntemlerinin sınırlarını aşabilirve kan-beyin bariyerinden olmaz terapötik maddelerin kullanımına izin verir ve bu nedenle, uygun bir tedavi seçenekleri 5, daha önce yok olmuştur. Sağlık ABD Ulusal Sağlık Enstitüleri (NIH) Araştırmacılar yalnız difüzyon 6-8 daha fazla terapötik ilaç konsantrasyonlarının ulaşmanın bir aracı olarak 1990&#39;ların başında CED nitelendirdi. CED ilk yöntemleri, beyin içine bir ya da daha yerleştirilmesi kateterler, kateterin bir enfüzyon pompası bağlayarak, ve hedef bölgeye doğrudan terapötik maddeleri pompalama içeriyordu. Artan kısım dağılımı ve nispeten kararlı konsantrasyonu infüzyon pompası ile oluşturulan pozitif basınç dokular genişletmek ve ilacın nüfuz 9 imkan vermek için neden olarak meydana geldiği bildirilmiştir. CED için temel teknik, büyük ölçüde ilk tarif edildiği gibi aynı kalır. Kateter tasarımı 10, infüzyon teknik ilerlemeler <sup&gt; 11, beyin vardiya 12, 13 düzeltmek birden doğrudaş İnfüzyonları 14 optimize ve infusate kaybı 15 izlemek için hat basıncı izleme 2, ve gerçek zamanlı MR izleme tedavinin 10 güvenliğini ve etkinliğini artırmıştır. Ek önem akış hızı dahil olmak üzere, kateter tasarımı ve infüzyon strateji yerleştirilmiştir. Başarılı CED, sınırlı kateter geri akış ve doku hasarı ile, kateter tasarımı ve infüzyon hızı ile korele edilmiştir. Dar bir çap ve kateter ucu 16 da beyin kateter arayüz boyunca geri akışını hem de sınır zararı en aza indirmek için düşük bir infüzyon oranı ile bir kateterin kullanılması. Ayrıca infüzyon reflü veya anormal teslim 17 düzeltilmesi için izin verirken MR görüntüleme, görsel infüzyon kateter yerleştirme için doğru konuma teyidini ve böylece ilaç teslim sağlar. MR görüntüleri de Vd (dağıtım hacimleri yaklaşık ve izlemek için kullanılabilir) Infüzyon ilacın. Vd segmentasyon 18 için bir eşik değeri olarak çevreleyen, infüzyon jelden ortalama yukarıdaki üç standart sapmadan daha büyük, bir MR sinyal yoğunluğunu değer kullanılarak hesaplanır. Beyindeki dağıtılan ilacın hacmini temsil ettiği Vd CED için yararlı bir ölçüdür. (Vi) infüzyon hacmi ile birlikte, bir ilaç infüzyon oranı kapsadığı hacim miktarının (Vd / Vi) oluşturulabilir. Vd, jel-kateter etkileşimleri, poroelastic özellikleri ve infüzyon bulut morfolojisi 10: Agaroz jel hayaletler gibi CED anlamak için önemli bir insan beyninin birçok önemli mekanik özelliklerini taklit. % 0.2 agaroz jel karışımları nedeniyle CED jel dilatasyon neden olduğu lokal gözenek fraksiyonu in vivo değişiklikleri taklit ettiği gösterilmiştir. Insan beynine benzer bir gözenek fraksiyonu benzer etkileşimleri ve Vd&#39;nin 19 doğru ölçümler teşvik etmektedir. A Ek olarak, benzer konsantrasyonlardagibi% 0.6 ve% 0.8 olarak garose jeller beyin 20 benzer infüzyon basınç profillerini göstermektedir. Bundan başka, saydam agaroz jelleri kateter ve infüzyon geri akış gerçek zamanlı görselleştirme avantaj sağlar. Agaroz jel hayalet üretmek için nispeten ucuzdur. Agarozjel fantomların maliyeti nörolojik ameliyat boyunca gelecek yaygın eğitime anahtar olabilir. Bu özelliklerinden dolayı, agaroz jeller beyin dokusunun kullanmadan insan beyni infüzyon en önemli özellikleri birçok kopyalayan, yararlı bir vekil sağlamaktadır. Yukarıda belirtildiği gibi, agaroz jel modellerine CED görüntü kılavuzlu test, araştırma ve eğitim için bir in vitro yöntem yararlı sağlar. Bu makalenin amacı, agaroz jel hayaletleri yeniden nasıl açıklamak için uygun CED test ve analiz protokolleri anahat ve nörolojik hastalığın tedavisi için CED infüzyon sırasında karşılaştığı ortak hataları hitap etmektir.

<table border="0" cellpadding="0" cellspacing="0" width="590">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Prohance</td>
			<td style="width:71px;">Bracco</td>
			<td style="width:119px;"></td>
			<td style="width:195px;">Gadoteridol radio contrast media</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Bromophenol Blue Dye</td>
			<td style="width:71px;">Biorad</td>
			<td style="width:119px;">161-0404</td>
			<td>Dye for infusate visualization</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Agarose Gel Powder</td>
			<td style="width:71px;">Biorad</td>
			<td style="width:119px;">161-3101EDU</td>
			<td>Agarose powder for creating gels</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">Medrad Veris MR Vital Signs Monitor</td>
			<td style="width:71px;">Medrad</td>
			<td style="width:119px;"></td>
			<td>MR safe infusion pressure monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">16 Gauge SmartFlow Catheter</td>
			<td style="width:71px;">SurgiVision</td>
			<td style="width:119px;"></td>
			<td>Infusion catheter</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">Medrad Continuum MR Infusion System</td>
			<td style="width:71px;">Medrad</td>
			<td style="width:119px;"></td>
			<td>MR safe infusion pump</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">SMART Frame MRI Guided Trajectory Frame</td>
			<td style="width:71px;">ClearPoint</td>
			<td style="width:119px;"></td>
			<td>Infusion catheter frame</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:205px;">Osirix Imaging Software and DICOM Viewer</td>
			<td style="width:71px;">Osirix Imaging Software</td>
			<td style="width:119px;"></td>
			<td>OsiriX 32-bit DICOM Viewer</td>
		</tr>
	</tbody>
</table>

image-guided convection-enhanced delivery into agarose gel models of the brain

Konveksiyon geliştirilmiş teslim (CED) nörolojik hastalıkların geniş bir yelpazede için bir tedavi seçeneği olarak öne sürülmüştür. Neuroinfusion kateter CED geleneksel ilaç dağıtım yöntemlerine göre bir intrakranial hedef tedavilerin büyük miktarlarda sunmak için pozitif basınçlı toplu akışı sağlar. Gerçek zamanlı MRG klinik yarar CED (rCED) rehberliğinde doğru, hedef, monitör tedavisi ve komplikasyonları belirlemek için yeteneği yatıyor. Eğitim ile rCED etkilidir ve komplikasyonları en aza indirilebilir. Beynin agarozjel modeli CED test, araştırma ve eğitim için erişilebilir bir araç sağlar. Ayrıca infüzyon görsel geribildirim sağlarken benzetilmiş beyin rCED sahte cerrahi uygulama sağlar. Infüzyon Analizler, insan beyin dokusu ile karşılaştırıldığında, acemi modelin benzerlik doğrulamak için izin dağıtım fraksiyonu (Vd / Vi) hesaplanması için olanak sağlar. Bu makale bizim agarozjel beyin fantom açıklar ve önemli beni özetliyornörolojik hastalığın tedavisi için CED infüzyon sırasında karşılaştığı ortak tuzaklar hitap ederken bir CED infüzyon ve analiz protokolleri sırasında Trics.

Sözlü ve CED enfüzyonları analiz gibi dağıtım fraksiyonu ve infusate reflü gibi birçok önemli faktörler içerir. Dağıtım kesir hesaplama Vd&#39;nin hesaplama üzerine büyük ölçüde bağlıdır. Bu nedenle MR görüntüleri doğru yorumlanması kritiktir. Biz yukarıda listelenen güvenilir bu ölçümleri üreyen için bir yarı-otomatik bir yöntem öneriyoruz. Bu yöntemler, objektif olarak infusate bulut enine kesit alanına ve yaklaşık bir yarıçapı belirler. Değişken, agaroz jeli içinde inf...

Watch this Scientific Journal Video about Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain at JoVE.com

Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain

Konveksiyon geliştirilmiş teslim (CED) nörolojik hastalıkların geniş bir yelpazede için bir tedavi seçeneği olarak öne sürülmüştür. CED kabulü için sağlık uzmanları hazırlamak için, ulaşılabilir eğitim modellerine ihtiyaç vardır. Bu test, araştırma ve eğitim için insan beyninin bir model olarak agaroz jel kullanımını tarif etmektedir.

Beyin Agaroz Jel Modelleri içine görüntü eşliğinde Konveksiyon geliştirilmiş Teslim

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. Neuroinfusion catheter CED allows ...

image-guided-convection-enhanced-delivery-into-agarose-gel-models

Research

JoVE Journal

Medicine

11.3K Görüntüleme.  University of Tennessee Health Science Center.  Konveksiyon geliştirilmiş teslim (CED) nörolojik hastalıkların geniş bir yelpazede için bir tedavi seçeneği olarak öne sürülmüştür. CED kabulü için sağlık uzmanları hazırlamak için, ulaşılabilir eğitim modellerine ihtiyaç vardır. Bu test, araştırma ve eğitim için insan beyninin bir model olarak agaroz jel kullanımını tarif etmektedir. 

Video: Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.

We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

Tıp

Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high molecular weight compounds from the bloodstream and into brain tissue. Some direct delivery success in humans has been achieved via implantation of transcranial catheters; however this method is highly invasive and associated with numerous complications. A less invasive alternative would be to dose the brain through a surgically implanted, semipermeable membrane such as the nasal mucosa that is used to repair skull base defects following endoscopic transnasal tumor removal surgery in humans. Drug transfer though this membrane would effectively bypass the BBB and diffuse directly into the brain and cerebrospinal fluid. Inspired by this approach, a surgical approach in mice was developed that uses a donor septal mucosal membrane engrafted over an extracranial surgical BBB defect. This model has been shown to effectively allow the passage of high molecular weight compounds into the brain. Since numerous drug candidates are incapable of crossing the BBB, this model is valuable for performing preclinical testing of novel therapies for neurological and psychiatric diseases.

A mouse model of human endoscopic skull base reconstruction has been developed that creates a semipermeable interface between the brain and nose using nasal mucosal grafts. This method allows researchers to study delivery to the central nervous system of high molecular weight therapeutics which are otherwise excluded by the blood-brain barrier when administered systemically.

Farelerde Beyin Doğrudan İlaç Teslim heterotopik mukozal aşılanması Prosedürü

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high ...

Mouse Kidney Transplantation: Models of Allograft Rejection

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

Here, we present a protocol to study the immunology of rejection. The surgical model presented reports a short operating time and a concise technique. Depending on the donor-recipient strain combination, the transplanted kidney may develop acute cellular rejection or chronic allograft damage, defined by interstitial fibrosis and tubular atrophy.

Fare Böbrek Transplantasyonu: Allogreft Reddi Modelleri

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma

An urgent need exists to test the contribution of new genes to the pathogenesis and progression of human glioblastomas (GBM), the most common primary brain tumor in adults with dismal prognosis. New potential therapies are rapidly emerging from the bench and require systematic testing in experimental models which closely reproduce the salient features of the human disease. Herein we describe in detail a method to induce new models of GBM with transposon-mediated integration of plasmid DNA into cells of the subventricular zone of neonatal mice. We present a simple way to clone new transposons amenable for genomic integration using the Sleeping Beauty transposon system and illustrate how to monitor plasmid uptake and disease progression using bioluminescence, histology and immuno-histochemistry. We also describe a method to create new primary GBM cell lines. Ideally, this report will allow further dissemination of the Sleeping Beauty transposon system among brain tumor researchers, leading to an in depth understanding of GBM pathogenesis and progression and to the timely design and testing of effective therapies for patients.

Here we describe an efficient and versatile protocol to induce, monitor and analyze novel glioblastomas (GBM) using transposon DNA injected into the ventricles of neonatal mice. Cells of the subventricular zone, which take up the plasmid, transform, proliferate and generate tumors with histo-pathological characteristics of human GBM.

Yenidoğan Fareler subventricular Bölgesi içine Plazmid DNA Transpozon Aracılı Entegrasyon Glioblastoma&#39;nın Roman modelleri oluşturmak için

An urgent need exists to test the contribution of new genes to the pathogenesis and progression of human glioblastomas (GBM), the most common primary ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 &#177; 80 &#937; cm2, and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10-6 &#177; 0.13 10-6 cm sec-1 (mean &#177; SEM, n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking.

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

The aim of the protocol is to present an optimized procedure for the establishment of an in vitro blood-brain barrier (BBB) model based on primary porcine brain endothelial cells (pBECs). The model shows high reproducibility, high tightness, and is suitable for studies of transport and intracellular trafficking in drug discovery.

Yöntem bir Vitro kan - beyin bariyerini modeli domuz beyin endotel hücreleri temel alan kurulması için geliştirilmiş

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Insulin regulates systematic metabolism in the hypothalamus and the peripheral insulin response. An inflammatory reaction in peripheral adipose tissues contributes to type 2 diabetes mellitus (T2DM) development and appetite regulation in the hypothalamus. Chemokine CCL5 and C-C chemokine receptor type 5 (CCR5) levels have been suggested to mediate arteriosclerosis and glucose intolerance in type 2 diabetes mellitus (T2DM). In addition, CCL5 plays a neuroendocrine role in the hypothalamus by regulating food intake and body temperature, thus, prompting us to investigate its function in hypothalamic insulin signaling and the regulation of peripheral glucose metabolism.
The micro-osmotic pump brain infusion system is a quick and precise way to manipulate CCL5 function and study its effect in the brain. It also provides a convenient alternative approach to generating a transgenic knockout animal. In this system, CCL5 signaling was blocked by intracerebroventricular (ICV) infusion of its antagonist, MetCCL5, using a micro-osmotic pump. The peripheral glucose metabolism and insulin responsiveness was detected by the Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT). Insulin signaling activity was then analyzed by protein blot from tissue samples derived from the animals.
After 7-14 days of MetCCL5 infusion, the glucose metabolism and insulin responsiveness was impaired in mice, as seen in the results of the OGTT and ITT. The IRS-1 serine302 phosphorylation was increased and the Akt activity was reduced in mice hypothalamic neurons following CCL5 inhibition. Altogether, our data suggest that blocking CCL5 in the mouse brain increases the phosphorylation of IRS-1 S302 and interrupts hypothalamic insulin signaling, leading to a decrease in insulin function in peripheral tissues as well as the impairment of glucose metabolism.

This protocol studies the role of chemokine (C-C motif) ligand 5 (CCL5) in the hypothalamus by delivering an antagonist, MetCCL5, into the mouse brain using a micro-osmotic pump brain infusion system. This transient inhibition of CCL5 activity interrupted hypothalamic insulin signaling, leading to glucose intolerance and peripheral systemic insulin sensitivity.

Hipotalamik insülin sinyal fare beyin içine sürekli uyuşturucu infüzyon sistemi ile periferik glikoz intoleransı için eğitim

Insulin regulates systematic metabolism in the hypothalamus and the peripheral insulin response. An inflammatory reaction in peripheral adipose tissues ...

Image-Guided Resection of Glioblastoma and Intracranial Implantation of Therapeutic Stem Cell-seeded Scaffolds

Glioblastoma (GBM), the most common and aggressive primary brain cancer, carries a life expectancy of 12-15 months. The short life expectancy is due in part to the inability of the current treatment, consisting of surgical resection followed by radiation and chemotherapy, to eliminate invasive tumor foci. Treatment of these foci may be improved with tumoricidal human mesenchymal stem cells (MSCs). MSCs exhibit potent tumor tropism and can be engineered to express therapeutic proteins that kill tumor cells. Advancements in preclinical models indicate that surgical resection induces premature MSC loss and reduces therapeutic efficacy. Efficacy of MSC treatment can be improved by seeding MSCs on a biodegradable poly(lactic acid) (PLA) scaffold. MSC delivery into the surgical resection cavity on a PLA scaffold restores cell retention, persistence, and tumor killing. To study the effects of MSC-seeded PLA implantation on GBM, an accurate preclinical model is needed. Here we provide a preclinical surgical protocol for image-guided tumor resection of GBM in immune-deficient mice followed by MSC-seeded scaffold implantation. MSCs are engineered with lentiviral constructs to constitutively express and secrete therapeutic TNF&#945;-related apoptosis-inducing ligand (TRAIL) as well as green fluorescent protein (GFP) to allow fluorescent tracking. Similarly, the U87 tumor cells are engineered to express mCherry and firefly luciferase, providing dual fluorescent/luminescent tracking. While currently used for investigating stem cell mediated delivery of therapeutics, this protocol could be modified to investigate the impact of surgical resection on other GBM interventions.

Tumor-seeking therapeutic mesenchymal stem cells (MSCs) show promise as a treatment for invasive glioblastoma. Optimal transplantation involves delivery of MSCs into the tumor resection cavity on scaffolds. Here, preclinical techniques to study MSC treatment of glioblastoma are provided including: image-guided tumor resection; implantation of MSC-seeded scaffolds; and postoperative therapy tracking.

Görüntü güdümlü rezeksiyon Glioblastoma ve kafa içi tedavi kök hücre numaralı seribaşı iskele implantasyonu

Glioblastoma (GBM), the most common and aggressive primary brain cancer, carries a life expectancy of 12-15 months. The short life expectancy is due in ...

Predicting Treatment Response to Image-Guided Therapies Using Machine Learning: An Example for Trans-Arterial Treatment of Hepatocellular Carcinoma

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this study was to develop a method to predict response to intra-arterial treatment prior to intervention.
The method provides a general framework for predicting outcomes prior to intra-arterial therapy. It involves pooling clinical, demographic and imaging data across a cohort of patients and using these data to train a machine learning model. The trained model is applied to new patients in order to predict their likelihood of response to intra-arterial therapy.
The method entails the acquisition and parsing of clinical, demographic and imaging data from N patients who have already undergone trans-arterial therapies. These data are parsed into discrete features (age, sex, cirrhosis, degree of tumor enhancement, etc.) and binarized into true/false values (e.g., age over 60, male gender, tumor enhancement beyond a set threshold, etc.). Low-variance features and features with low univariate associations with the outcome are removed. Each treated patient is labeled according to whether they responded or did not respond to treatment. Each training patient is thus represented by a set of binary features and an outcome label. Machine learning models are trained using N - 1 patients with testing on the left-out patient. This process is repeated for each of the N patients. The N models are averaged to arrive at a final model.
The technique is extensible and enables inclusion of additional features in the future. It is also a generalizable process that may be applied to clinical research questions outside of interventional radiology. The main limitation is the need to derive features manually from each patient. A popular modern form of machine learning called deep learning does not suffer from this limitation, but requires larger datasets.

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. A method for predicting response to these therapies is proposed. The technique uses pre-procedural clinical, demographic, and imaging information to train machine learning models capable of predicting response prior to treatment.

Makine öğrenimi kullanarak görüntü destekli terapi tedavi öngörmede: hepatosellüler karsinom Trans-arter tedavisi için bir örnek

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this ...

An Image Guided Transapical Mitral Valve Leaflet Puncture Model of Controlled Volume Overload from Mitral Regurgitation in the Rat

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the risks of uncorrected MR and its poor prognosis are known, the longitudinal changes in cardiac function, structure and remodeling are incompletely understood. This knowledge gap has limited our understanding of the optimal timing for MR correction, and the benefit that early versus late MR correction may have on the left ventricle. To investigate the molecular mechanisms that underlie left ventricular remodeling in the setting of MR, animal models are necessary. Traditionally, the aorto-caval fistula model has been used to induce volume overload, which differs from clinically relevant lesions such as MR. MR represents a low-pressure volume overload hemodynamic stressor, which requires animal models that mimic this condition. Herein, we describe a rodent model of severe MR in which the anterior leaflet of the rat mitral valve is perforated with a 23G needle, in a beating heart, with echocardiographic image guidance. The severity of MR is assessed and confirmed with echocardiography, and the reproducibility of the model is reported.&#160;&#160;

A rodent model of left heart volume overload from mitral regurgitation is reported. Mitral regurgitation of controlled severity is induced by advancing a needle of defined dimensions into the anterior leaflet of the mitral valve, in a beating heart, with ultrasound guidance.&#160;

Sıçanda Mitral Regurgitation Kontrollü Hacim Aşırı Bir Görüntü Güdümlü Transapical Mitral Kapak BroşürÜ Delinme Modeli

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the ...

Intratracheal Administration of Dry Powder Formulation in Mice

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper introduces a noninvasive method of intratracheal delivery of dry powder formulation in mice. A dry powder loading device that consists of a 200 &#181;L gel loading pipette tip connected to an 1 mL syringe via a three-way stopcock is presented. A small amount of dry powder (1-2 mg) is loaded into the pipette tip and dispersed by 0.6 mL of air in the syringe. Because pipette tips are disposable and inexpensive, different dry powder formulations can be loaded into different tips in advance. Various formulations can be evaluated in the same animal experiment without device cleaning and dose refilling, thereby saving time and eliminating the risk of cross-contamination from residual powder. The extent of powder dispersion can be inspected by the amount of powder remaining in the pipette tip. A protocol of intubation in mouse with a custom-made light source and a guiding cannula is included. Proper intubation is one of the key factors that influences the intratracheal delivery of dry powder formulation to the deep lung region of the mouse.

Dry powder formulations for inhalation have great potential in treating respiratory diseases. Before entering human studies, it is necessary to evaluate the efficacy of the dry powder formulation in preclinical studies. A simple and noninvasive method of the administration of dry powder in mice through the intratracheal route is presented.

Farelerde Kuru Toz Formülasyonunun Intratrakial Yönetimi

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...