title: MRI-monitored intra-shunt local agent delivery of motexafin gadolinium: towards improving long-term patency of TIPS.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Meng
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Patrick
authors.initials: P
authors.lastname: Willis
authors.forename: Thomas
authors.initials: T
authors.lastname: Le
authors.forename: Stephanie
authors.initials: S
authors.lastname: Soriano
authors.forename: Erik
authors.initials: E
authors.lastname: Ray
authors.forename: Karim
authors.initials: K
authors.lastname: Valji
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008665:Metalloporphyrins / Q000008:administration & dosage*; D013552:Swine
chemical_list: D003287:Contrast Media; D008665:Metalloporphyrins; C437683:motexafin gadolinium