Christi M. Terry PhD, Presenter: Nothing to Disclose

Huan Li MD, Abstract Co-Author: Nothing to Disclose

Eugene Kholmovski PhD, Abstract Co-Author: Research grant, Siemens AG

Seong-Eun Kim PhD, Abstract Co-Author: Nothing to Disclose

Ilya Zhuplatov, Abstract Co-Author: Nothing to Disclose

Ramesh Rathi PhD, Abstract Co-Author: Research Director, Protherics PLC

Kirk Fowers PhD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Biodegradable thermosensitive injectable polymers are promising platforms for sustained drug delivery. The purpose of this study was to develop an in vivo imaging method to serially monitor ReGel after injection into the perivascular area for the prevention of AV graft stenosis.

Polytetrafluoroethylene grafts were placed between the carotid artery and jugular vein in nine pigs. At time points of 1-7 weeks after graft placement, ReGel was injected under ultrasound guidance (1-6 injections/animal) to the perivascular area of the vein-graft anastomoses. Within 1 hour of injection, the animals underwent MRI in a Siemens 3T scanner with bilateral radio frequency (RF) receive-only phased array dedicated 8-channel coils. ReGel relaxation time values of T1/T2=1700/600ms were determined in pilot studies. T2w 3D turbo spin echo (TSE) sequence with restore pulse and ReGel-optimized imaging parameters (TE/TR=142/550ms, ETL=17, voxel dimensions 0.7x0.7x0.7mm3) were applied to visualize the ReGel depot. Black-blood T1w 2D TSE sequence (TE/TR=8.6/800ms, ETL=9, voxel dimensions 0.6x0.6x2.0mm3) was applied to visualize graft/blood vessel lumens. Some animals were imaged again up to 2 weeks after initial injection to evaluate duration of MR signal. A ReGel/dye mixture was injected to the perivascular anastomosis region in 1 animal. One week later the animal was imaged by MR then euthanized and the ReGel depot was surgically exposed to validate the gel location indicated by MR.

After exposure to body temperature, liquid ReGel immediately formed a gel that caused a shadowing artifact on 2D ultrasound images that obscured the anastomoses. In contrast, in ReGel-optimized 3D TSE MR images, the gel yielded a strong signal greatly distinct from other tissues. In conjunction with the black-blood imaging, the spatial relationship of the ReGel depot to the blood vessels and anastomoses could be readily determined at least one week after injection. The veracity of ReGel MR images was confirmed by visual inspection of the dye-loaded gel at autopsy.

ReGel-optimized MRI allows for 3D visualization of the gel depot after injection and over time that could not be achieved with the 2D ultrasonography.

MRI visualization of gel location after injection will facilitate the use of novel thermosensitive injectable sustained-delivery platforms for the pharmacological prevention of vascular stenosis.

Terry, C, Li, H, Kholmovski, E, Kim, S, Zhuplatov, I, Rathi, R, Fowers, K, et al, , Serial Magnetic Resonance Imaging (MRI) to Monitor the Precise Location of a Biodegradable Thermal Gelling Copolymer (ReGel™) for Drug Delivery after Ultrasound-guided Injection in a Porcine Model of Arteriovenous (AV) Hemodialysis Graft Stenosis.  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/6006516.html