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Development of an intrabiliary MR imaging-monitored local agent delivery technique: a feasibility study in pigs.

ABSTRACT: PURPOSE: To investigate the feasibility of using magnetic resonance (MR) imaging to monitor intrabiliary delivery of motexafin gadolinium (MGd) into pig common bile duct (CBD) walls. MATERIALS AND METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee. Initially, human cholangiocarcinoma cells were treated with various concentrations of MGd, a compound serving as a T1-weighted MR imaging contrast agent, chemotherapy drug, and cell marker. These cells were then examined by means of confocal microscopy to confirm the intracellular uptake of MGd. In addition, an MGd/trypan blue mixture was locally infused into CBD walls of six cadaveric pigs using a microporous balloon catheter. CBDs of six pigs were infused with saline to serve as controls. Ex vivo T1-weighted MR imaging of these CBDs was performed. For in vivo technical validation, the microporous balloon catheter was placed in the CBD by means of a transcholecytic access to deliver MGd/trypan blue into CBD walls of six living pigs. T1-weighted images were obtained with both a surface coil and an intrabiliary MR imaging guidewire, and contrast-to-noise ratios of CBD walls before and after MGd/trypan blue infusions were compared in the two groups by means of paired t test, with subsequent histologic analysis to confirm the penetration and distribution of the MGd/trypan blue agent into CBD walls. RESULTS: In vitro experiments confirmed uptake of MGd by human cholangiocarcinoma cells. The ex vivo experiments demonstrated the penetration of MGd/trypan blue into the CBD walls. The in vivo experiment confirmed the uptake of MGd/trypan blue, showing an increased contrast-to-noise ratio for the CBD after administration of the mixture, compared with images obtained prior to MGd/trypan blue administration (11.6 ± 4.2 [standard deviation] vs 5.7 ± 2.8; P = .04). Histologic results depicted the blue dye stains and red fluorescence of MGd in CBD walls, confirming the imaging findings. CONCLUSION: It is feasible to use MR imaging to monitor the penetration of locally delivered MGd into pig CBD walls.

SUBMITTER: Zhang F

PROVIDER: S-EPMC3285228 | biostudies-other | 2012 Mar

REPOSITORIES: biostudies-other

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Project description:PurposeTo develop a technique with clinical 3.0-T magnetic resonance (MR) imaging to delineate local contrast agent distribution in coronary artery walls for potential molecular MR imaging-guided local gene or drug therapy of atherosclerotic coronary artery disease.Materials and methodsThis animal protocol was approved by the institutional animal care and use committee and was in compliance with the Guide for the Care and Use of Laboratory Animals. For in vitro confirmation, human arterial smooth muscle cells (SMCs) were used to determine capability of SMCs in uptake of motexafin gadolinium (MGd) and its optimal dose. For ex vivo evaluation, a 2-mL mixture of MGd and trypan blue was locally infused into coronary artery walls of six cadaveric pig hearts with MR monitoring and an MR imaging guidewire, surface coils, or both. For in vivo validation, the balloon catheter was placed into coronary arteries of seven living pigs, and the MGd and trypan blue mixture was infused into arterial walls with MR guidance. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of coronary artery walls were recorded by using different coils between pre- and postcontrast infusion, with subsequent histologic confirmation. Paired Student t tests were used to compare average SNRs and CNRs of arterial walls before and after contrast agent infusion with different coils.ResultsSMCs could take up MGd with the optimal concentration at 150 µmol/L. Average SNR with the MR imaging guidewire and surface coil combination was significantly higher than that with the MR imaging guidewire only or with surface coils only (P < .05), and average SNR and CNR of postinfusion MR imaging was significantly higher than that of preinfusion MR imaging (P < .05). Histologic analysis was used to confirm successful intracoronary infiltration of MGd and trypan blue within coronary artery walls.ConclusionMR imaging can be used to delineate locally infused contrast agent distribution in coronary artery walls. This establishes groundwork for development of molecular MR imaging-guided intracoronary therapy.

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Development of an intrabiliary MR imaging-monitored local agent delivery technique: a feasibility study in pigs.

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