Die Autoren möchten von der MRT-Einrichtungen des Semmes-Murphey Klinik, Memphis, Tennessee sowie der Neurochirurgischen Abteilung an der Universität von Tennessee Health Science Center in Memphis, Tennessee danke den Mitarbeitern.

1. Herstellung von Gel Phantoms und Dye <ol><li> Planen 0,2% Agarose-Gel durch Auflösen von 2 g 0,1%-Agarose-Pulver in 1000 ml deionisiertem Wasser. Rühren Sie die Lösung für ca. 1 min auf gute Durchmischung zu gewährleisten; Mikrowelle und sofort die Lösung in 3-Minuten-Intervallen für 9 min oder bis klar ist, Rühren zwischen den Intervallen. </li><li> Während das Agarosegel flüssig ist, die Lösung auf 5 cm x 5 cm x 5 cm Behälter. Lassen Sie Platz an der Spitze des Behälters mit Wasser hinzufügen und damit die Agarose-Gel zu kühlen und zu begleichen. </li><li> Sobald die Agarose-Gel (ca. 1-2 Std.) verfestigt, fügen Sie 1 cm Wasser an die Spitze des Gels und im Kühlschrank lagern. Es ist am besten, um das Gel innerhalb von 24-48 h Mischen verwenden, aber es kann gespeichert werden für bis zu einer Woche im Kühlschrank 10. </li><li> Vorbereitung eines Radiokontrastmittel in einer 60 ml-Spritze, die aus 50 ml der 0,017% Bromphenolblau-Farbstoff (BPB) und 2 mM Gadoteridol Radiokontrastmittel. <ol><li> Kombinieren 8,5 mg Farbstoff BPB zu 50 ml VE-Wasser, um eine 0,017% BPB-Lösung zu schaffen. </li><li> In 0,2 ml 0,5 M Gadoteridol Lager an die 50 ml 0,017% BPB Lösung, um eine 2 mM Gadoteridol Lösung zu schaffen. </li></ol></li></ol> 2. Vorbereitung der Infusion System <ol><li> Spritzenpumpe Infusionssystem (bevorzugte Methode): Zur Herstellung einer Spritzenpumpe, befestigen den Infusionskatheter direkt mit der Spritze durch den Drucksensor, wodurch das Totvolumen der Infusionsleitung. Die Spülfunktion der Spritzenpumpe verwendet werden, um die Linie der Luft klar unter Verwendung eines Bolus größer als der Füllvolumen des Katheters mit einer Rate von 10 ul / min. </li><li> Schlauchpumpe Infusionssystem (alternative Methode): Verbinden Sie die Spritze mit der Radio-Kontrastmittel mit der Infusionspumpe. Befestigen Sie den Drucksensor an der Pumpenausgang mit dem Wandler an die IV-Monitor angebracht. Anfügen einer 16 G Infusionskatheter an dem offenen Ende des Drucksensors. Hinweis: Die Spitze des 16 G Infusionskatheter hat einen InnendurchmesserMesser von 0,2 mm und einem Außendurchmesser von 0,35 mm. Die Spitze ist aus Quarzglas und die Spitzenlänge beträgt 3 mm. Es erhöht sich auf etwa 0,75 mm und geht seit 15 mm, werden die Schritte der Katheter in einer Art und Weise verjüngt auf 1,6 mm oder 16 G. </li><li> Bereiten Sie sich für Infusion durch Spülen des Systems für ca. 15 min bei 16.667 ml / min, um Luftblasen zu entfernen. Die 16.667 ul / min Durchflussmenge darf nicht überschritten werden, da die Maschine Infusion aufgrund der hohen Leitungsdruck einzustellen. Nach Anbringen des Infusionskatheter zur Linie Verlassen der Infusionspumpe, Spülungsleitungen von Luft durch die Verwendung der Funktion &quot;Bolus&quot; auf der Infusionspumpe. </li><li> Befestigen Sie die Infusionskatheter montieren und Flugbahn Rahmen auf das Gel Phantombehälter (5 cm x 5 cm x 5 cm) und in der MRT. </li></ol> 3. CED Gel Infusions-und MR-Scanning <ol><li> Null den Druckwert (mmHg) durch die IV-Monitor vor Beginn der Infusion aufgezeichnet. </li><li> Legen Sie die Infusionskatheter in die Agarose-Gel-with die Infusionspumpe läuft bei der niedrigsten Strömungsgeschwindigkeit möglich, in diesem Fall 1,667 ul / min. </li><li> Beginnen die MR-Scan, mit den in Tabelle 1 aufgeführten Parameter und die Infusion mit einer Geschwindigkeit von 1,667 ml / min. Infuse das Gel mit einer konstanten Rate, bis das Gesamtvolumen infundiert 60 ul (ca. 38 min) erreicht. </li><li> Scannen des Gels kontinuierlich in 3 Minuten und 50 Sekunden Abständen. Notieren Sie sich die Druckwerte alle 60 sek. Sobald das Volumen infundiert 60 ul erreicht, schalten Sie die Infusionspumpe; und vollständige MRT-Untersuchungen während weiterhin Druckwerte aufzuzeichnen. </li></ol> 4. MR Datenanalyse <ol><li> Für die Analyse der MR-Bilder, verwenden Sie ein entsprechendes DICOM-Viewer mit ROI-Segmentierung Funktionalität. </li><li> Wählen Sie den richtigen Rahmen in jedem Scan durch den Querschnitt des Katheters, wie in Abbildung 1 zu sehen ist markiert. </li><li> Mit Hilfe der &quot;ROI - Rechteck&quot;-Werkzeug, wählen Sie den größten Teil des Gels, das keine keineTeil der Infusionsstelle. Die Software ausgeben wird eine mittlere Pixeldichte mit Standardabweichung. Finden Sie den Wert, der drei Standardabweichungen vom Mittelwert entspricht. Dieser Wert wird als der Schwellenwert zur Bestimmung, wann Kontrast mit einem Vertrauen von 99,7% vorliegt verwendet. </li><li> Mit Hilfe der &quot;ROI - Kreis&quot; Werkzeug, umkreisen die Infusionsstelle mit einem ausreichend großen Kreis und geben diesem einen eindeutigen Namen. </li><li> Wählen Sie den Kreis und mit dem &quot;ROI - Set Pixelwerte zu&quot; Werkzeug in Schritt 4.3 in die Eingangsschwellenwert &quot;, wenn aktuelle Wert größer als:&quot;-Box und Häkchen nur diese Zeile. Dann in &quot;auf diesen neuen Wert:&quot; geben Sie einen großen Wert (25.000). Stellen Sie die Pixeldichte, um den Bereich von der vorher definierten Schwelle umfasste auswählen. </li><li> Weiter mit dem &quot;ROI - Region wachsen (2D/3D Segmentierung)&quot;-Werkzeug, wählen Sie 2D-Anbaugebiet, das Vertrauen Algorithmus mit Anfangsradius Parameter = 2, und Pinsel ROI. Klicken Sie in der Infusionsstelle für die Software, um die gesamte Fläche zu berechnen of diese Region. </li><li> Unter der Annahme einer sphärischen Infusions Wolke berechnen das Volumen der Diffusion aus der Umgebung über die folgende Gleichung: V = 4/3π (√ (Fläche / 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>

Die Autoren erklären, dass sie keine finanziellen Interessen konkurrieren.

<html> Die kritischen Schritte für den Erfolg der Infusion sind: Spülen der Infusionsleitung von Luft, das Mischen der Agarose-Gel, die Analyse der MR-Daten, mit kleinen Innendurchmessern Katheter mit abgestuften Katheterkonstruktionen, um einen Rückfluß zu minimieren und eine Minimierung der Druck, der durch den Filz Gel oder Gewebe, in das das Arzneimittel infundiert. Wie zuvor erwähnt, die Haupt Nachteil für den Erfolg der Infusion Infusionsleitung Luft. Richtig und gründlich Spülen des Infusionsleitung von Lu...

Konvektion Enhanced Delivery (CED) wurde als Behandlungsoption für ein breites Spektrum neurologischer Erkrankungen einschließlich bösartiger Hirntumoren, Epilepsie, Stoffwechselerkrankungen, neurodegenerativen Erkrankungen (wie Parkinson-Krankheit) 1, Schlaganfall und Trauma 2 vorgeschlagen. CED beschäftigt Druck Schüttstrom für den Vertrieb eines Arzneimittels oder anderen Infusionslösung. CED bietet sichere, zuverlässige, homogene und Lieferung von molekularen Verbindungen, die von niedrig bis hoch, in klinisch relevanten Mengen 3. Traditionelle Arzneimittelabgabe an Hirngewebe ist stark durch die Blut-Hirn-Schranke 4 beschränkt. Von den engen Verbindungen zwischen Endothelzellen, aus denen sich die Kapillaren in das Gehirn, die Blut-Hirn-Schranke Blöcke polaren und hochmolekulare Moleküle vom Betreten des Parenchym des Gehirns gebildet. Direkt intraparenchymal Gehirn Infusion über CED können die Einschränkungen der bisherigen therapeutischen Drug-Delivery-Modalitäten zu überwindenund ermöglicht die Verwendung von Therapeutika, die die Blut-Hirn-Schranke nicht überqueren würde, und haben daher bisher nicht als praktikable Behandlungsmöglichkeiten 5 gewesen. Forscher der US-amerikanischen National Institutes of Health (NIH) beschrieben CED in den frühen 1990er Jahren als ein Mittel zur Erreichung größere therapeutische Wirkstoffkonzentrationen als durch Diffusion allein 6-8. Die ersten Verfahren der CED beteiligt Implantieren eines oder mehrerer Katheter in das Gehirn, den Anschluss einer Infusionspumpe mit dem Katheter und Pumpen der therapeutische Mittel direkt in die Zielregion. Die erhöhte Bruchverteilung und relativ stabile Konzentration wird berichtet, auftreten, wie der positive Druck, der durch die Infusionspumpe bewirkt, dass die Gewebe zu erweitern und damit für das Eindringen des Drogen 9. Die grundlegende Technik für CED ist weitgehend das gleiche wie es zuerst beschrieben wurde. Fortschritte in der Katheter-Design 10, Infusionstechnik <sup&gt; 11, Zeile 2 Drucküberwachung und Echtzeit-Überwachung für MRI Brain Shift 12, 13 zu korrigieren, optimieren mehrere Infusionen kollinear 14, und Monitor für Infusions Verlust 15 haben die Sicherheit und Wirksamkeit der Behandlung 10 erhöht. Zusätzliche Bedeutung hat Design auf dem Katheter und Infusions Strategie, einschließlich Durchsatz gelegt. Erfolgreiche CED, mit begrenzten Katheterrückfluss-und Gewebeschäden, mit Katheter Design und Infusionsrate korreliert. Die Verwendung eines Katheters mit einem kleinen Durchmesser und einer niedrigen Infusionsgeschwindigkeit auf Rückfluss entlang der Gehirnkatheter Schnittstelle sowie Schadensbegrenzung an der Katheterspitze 16 zu begrenzen. MR-Bildgebung bietet visuelle Bestätigung der korrekten Position für Infusionskatheter Platzierung, und damit Medikamentenabgabe, aber dabei auch für die Korrektur der Infusions Reflux oder abweichende Liefer 17. MR-Bilder können auch verwendet werden, um zu approximieren und verfolgen die Verteilungsvolumina (Vd werden) Des infundierten Medikaments. Vd unter Verwendung eines MR-Bildgebungssignalstärkewert größer als drei Standardabweichungen über dem Mittelwert von der umgebenden nicht-infundierten Gel als Schwellenwert für die Segmentierung 18 berechnet. Vd ist ein nützliches Maß für CED weil es das Volumen des Arzneimittels im Gehirn verteilt darstellt. Zusammen mit dem infundierten Volumen (Vi), kann ein Verhältnis erzeugt werden (Vd / Vi) Quantifizieren der von der infundierten Volumen Medikament bedeckt. Agarose-Gel-Phantome imitieren mehrere entscheidende mechanischen Eigenschaften des menschlichen Gehirns wichtig für das Verständnis, wie CED: Vd, Gel-Katheter-Interaktionen, poroelastischen Eigenschaften und Infusions Cloud Morphologie 10. Mischungen von 0,2% Agarosegel wurde gezeigt, dass in vivo Veränderungen der lokalen Porenanteil durch Gel Dilatation durch CED verursacht imitieren. Eine ähnliche Porenanteil menschliche Gehirn fördert ähnliche Wechselwirkungen und genaue Messungen von Vd 19. Zusätzlich, ähnlich den Konzentrationen agarose Gele wie 0,6% und 0,8% haben ähnliche Profile Infusionsdruck an das Gehirn 20 gezeigt. Ferner werden die durchscheinenden Agarosegelen den Vorteil einer Echtzeit-Darstellung der Katheterplatzierung und Infusions Rückfluß. Agarose-Gel-Phantome sind relativ preiswert zu produzieren. Die Kosten für die Agarose-Gel-Phantome Schlüssel zur Zukunft weit verbreitete neurologische Ausbildung während der Operation. Aufgrund dieser Eigenschaften Agarosegelen eine nützliche Ersatz Replizieren viele der wichtigsten Attribute des menschlichen Gehirns Infusionen ohne die Verwendung von Hirngewebe. Wie oben angegeben, Bild-geführte CED in Agarose-Gel-Modelle bietet eine vorteilhafte In-vitro-Verfahren zur Prüfung, Forschung und Ausbildung. Der Zweck dieses Artikels ist es zu beschreiben, wie Agarose-Gel Phantome neu zu erstellen, um geeignete CED Test-und Analyseprotokolle erläutern und gemeinsame Fehler bei der CED-Infusionen zur Behandlung von neurologischen Erkrankung konfrontiert sind.

<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

Konvektion Enhanced Delivery (CED) wurde als Behandlungsmöglichkeit für eine Vielzahl von neurologischen Erkrankungen vorgeschlagen. Neuroinfusion Katheter CED ermöglicht Druck Schüttstrom, größere Mengen von Therapeutika auf eine intrakranielle Ziel als herkömmliche Arzneimittelverabreichungsmethoden zu liefern. Der klinische Nutzen der Echtzeit-MRT-geführte CED (RCED) liegt in der Fähigkeit, genau zu zielen, zu überwachen Therapie und Komplikationen zu identifizieren. Mit Ausbildung ist RCED effiziente und Komplikationen minimiert werden. Die Agarose-Gel-Modell des Gehirns bietet eine zugängliche Tool für CED Prüfung, Forschung und Ausbildung. Simulierte Gehirn RCED ermöglicht Praxis der Scheinoperation während auch visuelle Rückmeldung der Infusion. Analyse der Infusion gestattet Berechnung der Verteilung Fraktion (Vd / Vi), so dass der Trainee, um die Ähnlichkeit des Modells zu überprüfen, verglichen mit menschlichen Hirngewebe. Dieser Artikel beschreibt unsere Agarose-Gel-Phantom Gehirn und weist auf wichtige michtrics während einer CED Infusions-und Analyseprotokolle beim Adressieren häufigsten Fallstricke bei CED konfrontiert Infusion zur Behandlung von neurologischen Erkrankungen.

Interpretation und Analyse von CED Infusionen umfassen mehrere wichtige Faktoren wie Verteilungsfraktion und Infusions Reflux. Die Verteilung Bruchrechnung hängt stark von der Berechnung der Vd. Daher genaue Interpretation der MR-Bilder, ist kritisch. Wir schlagen ein halbautomatisches Verfahren zum zuverlässigen Wiedergeben dieser Messungen wie oben aufgeführt. Diese Verfahren objektiv bestimmen die Querschnittsfläche des Infusions Wolke und eine ungefähre Radius. Während variabel, in Agarose-Gel die Infusion Wol...

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

Konvektion Enhanced Delivery (CED) wurde als Behandlungsmöglichkeit für eine Vielzahl von neurologischen Erkrankungen vorgeschlagen. Um Fachkräfte des Gesundheitswesens für die Annahme der CED vorzubereiten, werden zugänglich Ausbildungsmodelle notwendig. Wir beschreiben die Verwendung von Agarose-Gel als solches Modell des menschlichen Gehirns, die für Tests, Forschung und Ausbildung.

Bildgestützte Konvektion-enhanced Lieferung in Agarose-Gel-Modelle des Gehirns

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 Aufrufe.  University of Tennessee Health Science Center.  Konvektion Enhanced Delivery (CED) wurde als Behandlungsmöglichkeit für eine Vielzahl von neurologischen Erkrankungen vorgeschlagen. Um Fachkräfte des Gesundheitswesens für die Annahme der CED vorzubereiten, werden zugänglich Ausbildungsmodelle notwendig. Wir beschreiben die Verwendung von Agarose-Gel als solches Modell des menschlichen Gehirns, die für Tests, Forschung und Ausbildung. 

Serie: 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 ...

Forschung

Medizin

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.

Heterotope Mucosal-Transplantationsverfahren für Direkt Drug Delivery zum Gehirn bei Mäusen

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.

Maus Nierentransplantation: Modelle der Transplantatabstoßung

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.

Transposon-vermittelte Integration von Plasmid-DNA in die Subventrikularzone von neugeborenen Mäusen zu Novel Modelle von Glioblastoma generieren

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.

Verbesserte Methode für die Einrichtung einer In-vitro- Blut - Hirn-Schranke Modell auf porcinen Endothelzellen Gehirnzellen basiert

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.

Studium der Hypothalamus Insulin-Signal an peripheren Glukoseintoleranz mit einem kontinuierlichen Medikament Infusion System in das Gehirn der Maus

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.

Bildgestützte Resektion der Glioblastom und intrakraniellen Implantation von therapeutischen Stammzellen entkernt Gerüste

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.

Vorhersage der Behandlungserfolg für bildgestützte Therapien mit maschinellem lernen: ein Beispiel für eine Trans-arterielle Behandlung des hepatozellulären Karzinoms

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;

Ein Bild geführte transapical Mitral Valve Leaflet Puncture Modell der kontrollierten Volumenüberlastung von Mitral Regurgitation in der Ratte

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.

Intratrachealadministration der Trockenpulverformulierung bei Mäusen

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