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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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Related in: MedlinePlus

Confocal microscopic images of SMCs incubated with MGd at various concentrations of 0 to 150 µg/mL.The images demonstrate that an increased intracellular uptake of MGd in cytoplasm (red fluorescent dots) as MGd concentration increases.
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pone-0057419-g003: Confocal microscopic images of SMCs incubated with MGd at various concentrations of 0 to 150 µg/mL.The images demonstrate that an increased intracellular uptake of MGd in cytoplasm (red fluorescent dots) as MGd concentration increases.

Mentions: In the in vitro experiments, confocal microscopy confirmed the intracellular uptake of MGd by SMCs, showing an increased MGd uptake as the MGd concentrations increased (Figure 3). In vitro T1-map MRI further confirmed these cytologic findings, demonstrating a linear decrease of T1 value from 0 to 100-mg/mL and then a platform pattern of T1 values from 100 to 150 mg/mL of MGd (Figure 4). MTS assay showed that the proliferation levels of SMCs decreased as the MGd concentrations increased and as the MGd-treating times increased (Figure 5).


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)

Confocal microscopic images of SMCs incubated with MGd at various concentrations of 0 to 150 µg/mL.The images demonstrate that an increased intracellular uptake of MGd in cytoplasm (red fluorescent dots) as MGd concentration increases.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585394&req=5

pone-0057419-g003: Confocal microscopic images of SMCs incubated with MGd at various concentrations of 0 to 150 µg/mL.The images demonstrate that an increased intracellular uptake of MGd in cytoplasm (red fluorescent dots) as MGd concentration increases.
Mentions: In the in vitro experiments, confocal microscopy confirmed the intracellular uptake of MGd by SMCs, showing an increased MGd uptake as the MGd concentrations increased (Figure 3). In vitro T1-map MRI further confirmed these cytologic findings, demonstrating a linear decrease of T1 value from 0 to 100-mg/mL and then a platform pattern of T1 values from 100 to 150 mg/mL of MGd (Figure 4). MTS assay showed that the proliferation levels of SMCs decreased as the MGd concentrations increased and as the MGd-treating times increased (Figure 5).

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