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MRI-monitored intra-shunt local agent delivery of motexafin gadolinium: towards improving long-term patency of TIPS.

Wang H, Zhang F, Meng Y, Zhang T, Willis P, Le T, Soriano S, Ray E, Valji K, Zhang G, Yang X - PLoS ONE (2013)

Bottom Line: Shunts were harvested for subsequent histology confirmation.In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well.Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS.

Methodology: Human umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation.

Principal findings: In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.

Conclusion: Results of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd functions as a potential therapeutic agent to inhibit the proliferation of SMCs, which may open alternative avenues to improve the long-term patency of TIPS.

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Main steps of the TIPS procedure with local MGd delivery into the shunt-vein wall.Simultaneous venograms show the location and length of the shunt between the right portal vein (open arrow) and the right hepatic vein (closed arrow) (a). Placement of the custom-made microporous balloon for the agent delivery into the shunt-vein wall. Arrowheads indicate the two markers of the balloon (b). A deployed stent (arrowhead) through the TIPS shunt (c). Post-procedure venogram shows that the contrast in the main portal vein (open arrow) is flowing though TIPS shunt (curved arrow) into the hepatic vein (closed arrow) (d).
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pone-0057419-g002: Main steps of the TIPS procedure with local MGd delivery into the shunt-vein wall.Simultaneous venograms show the location and length of the shunt between the right portal vein (open arrow) and the right hepatic vein (closed arrow) (a). Placement of the custom-made microporous balloon for the agent delivery into the shunt-vein wall. Arrowheads indicate the two markers of the balloon (b). A deployed stent (arrowhead) through the TIPS shunt (c). Post-procedure venogram shows that the contrast in the main portal vein (open arrow) is flowing though TIPS shunt (curved arrow) into the hepatic vein (closed arrow) (d).

Mentions: All pigs were first sedated by intramuscular injection of Telazol at 4.4 mg/kg body weight and Xylazine at 1 mg/kg body weight, and then mechanically ventilated with 1–3% isoflurane. The pigs subsequently underwent TIPS procedures in an angiography suite. Briefly, the right jugular vein was accessed by a 4-F micro-puncture set (MPIK-4-SP7, B. Braun Medical Inc., Bethlehem, PA) under ultrasound guidance. A 10-F TIPS set (RUPS-100, Cook Medical., Bloominton, IN) was then advanced, via the superior vena cava and the right atrium of the heart, into a hepatic vein. Once successful puncture of the portal vein was achieved, a 260-cm-long, 0.035-inch steerable guide wire (Back-up Meier, Boston Scientific, Miami, FL) was advanced into the superior mesenteric vein (SMV). After placing a 90-cm-long, 5-F gold marker pigtail catheter (Royal Flush, Cook Medical, Bloominton, IN) in the SMV and a 40-cm-long, 10-F TIPS sheath into the hepatic vein over the guidewire, simultaneous venograms were obtained by (i) power injection of 14-mL nonionic contrast medium (iohexol [Omnipaque], 300 mg of iodine per milliliter, GE Healthcare Inc., Princeton, NJ) at 7 mL/sec for three seconds using an automatic injection system (Stellant Dual, Medrad Inc., Pittsburgh, PA) from the pigtail catheter; and (ii) manual injection of 15-mL contrast agent at 50% concentration at approximately 5 mL/sec for three seconds. The simultaneous venograms enabled us to determine the length of the created parenchymal tract (shunt) between the hepatic vein and the portal vein. Then, a 6 mm×4 cm custom-made microporous delivery balloon catheter was placed into the shunt with the center of the balloon just across the junction of the hepatic vein to the shunt. The MGd delivery balloon catheter consisted of an angioplasty balloon with multiple micropores on the balloon surface. The inflation of the balloon with MGd stopped the blood flow completely in the vessel and simultaneously propelled the micropores against the targeted vessel wall. Thus, subsequent infusion of the MGd caused, via an orifice-mediated jet effect, the disruption of the physical barriers imposed by the continuous endothelium and the internal elastic lamina, and, thereby, the delivery of MGd into the media of the targeted vessel wall. Figure 2 shows the main steps of the TIPS procedure, with local delivery of MGd into the shunt-vein walls.


MRI-monitored intra-shunt local agent delivery of motexafin gadolinium: towards improving long-term patency of TIPS.

Wang H, Zhang F, Meng Y, Zhang T, Willis P, Le T, Soriano S, Ray E, Valji K, Zhang G, Yang X - PLoS ONE (2013)

Main steps of the TIPS procedure with local MGd delivery into the shunt-vein wall.Simultaneous venograms show the location and length of the shunt between the right portal vein (open arrow) and the right hepatic vein (closed arrow) (a). Placement of the custom-made microporous balloon for the agent delivery into the shunt-vein wall. Arrowheads indicate the two markers of the balloon (b). A deployed stent (arrowhead) through the TIPS shunt (c). Post-procedure venogram shows that the contrast in the main portal vein (open arrow) is flowing though TIPS shunt (curved arrow) into the hepatic vein (closed arrow) (d).
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Related In: Results  -  Collection

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pone-0057419-g002: Main steps of the TIPS procedure with local MGd delivery into the shunt-vein wall.Simultaneous venograms show the location and length of the shunt between the right portal vein (open arrow) and the right hepatic vein (closed arrow) (a). Placement of the custom-made microporous balloon for the agent delivery into the shunt-vein wall. Arrowheads indicate the two markers of the balloon (b). A deployed stent (arrowhead) through the TIPS shunt (c). Post-procedure venogram shows that the contrast in the main portal vein (open arrow) is flowing though TIPS shunt (curved arrow) into the hepatic vein (closed arrow) (d).
Mentions: All pigs were first sedated by intramuscular injection of Telazol at 4.4 mg/kg body weight and Xylazine at 1 mg/kg body weight, and then mechanically ventilated with 1–3% isoflurane. The pigs subsequently underwent TIPS procedures in an angiography suite. Briefly, the right jugular vein was accessed by a 4-F micro-puncture set (MPIK-4-SP7, B. Braun Medical Inc., Bethlehem, PA) under ultrasound guidance. A 10-F TIPS set (RUPS-100, Cook Medical., Bloominton, IN) was then advanced, via the superior vena cava and the right atrium of the heart, into a hepatic vein. Once successful puncture of the portal vein was achieved, a 260-cm-long, 0.035-inch steerable guide wire (Back-up Meier, Boston Scientific, Miami, FL) was advanced into the superior mesenteric vein (SMV). After placing a 90-cm-long, 5-F gold marker pigtail catheter (Royal Flush, Cook Medical, Bloominton, IN) in the SMV and a 40-cm-long, 10-F TIPS sheath into the hepatic vein over the guidewire, simultaneous venograms were obtained by (i) power injection of 14-mL nonionic contrast medium (iohexol [Omnipaque], 300 mg of iodine per milliliter, GE Healthcare Inc., Princeton, NJ) at 7 mL/sec for three seconds using an automatic injection system (Stellant Dual, Medrad Inc., Pittsburgh, PA) from the pigtail catheter; and (ii) manual injection of 15-mL contrast agent at 50% concentration at approximately 5 mL/sec for three seconds. The simultaneous venograms enabled us to determine the length of the created parenchymal tract (shunt) between the hepatic vein and the portal vein. Then, a 6 mm×4 cm custom-made microporous delivery balloon catheter was placed into the shunt with the center of the balloon just across the junction of the hepatic vein to the shunt. The MGd delivery balloon catheter consisted of an angioplasty balloon with multiple micropores on the balloon surface. The inflation of the balloon with MGd stopped the blood flow completely in the vessel and simultaneously propelled the micropores against the targeted vessel wall. Thus, subsequent infusion of the MGd caused, via an orifice-mediated jet effect, the disruption of the physical barriers imposed by the continuous endothelium and the internal elastic lamina, and, thereby, the delivery of MGd into the media of the targeted vessel wall. Figure 2 shows the main steps of the TIPS procedure, with local delivery of MGd into the shunt-vein walls.

Bottom Line: Shunts were harvested for subsequent histology confirmation.In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well.Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS.

Methodology: Human umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation.

Principal findings: In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.

Conclusion: Results of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd functions as a potential therapeutic agent to inhibit the proliferation of SMCs, which may open alternative avenues to improve the long-term patency of TIPS.

Show MeSH
Related in: MedlinePlus