Parag V. Karmarkar

Magnetic resonance–guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells

In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance–trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic β-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse β-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.

MR-trackable intramyocardial injection catheter

There is growing interest in delivering cellular agents to infarcted myocardium to prevent postinfarction left ventricular remodeling. MRI can be effectively used to differentiate infarcted from healthy myocardium. MR‐guided delivery of cellular agents/therapeutics is appealing because the therapeutics can be precisely targeted to the desired location within the infarct. In this study, a steerable intramyocardial injection catheter that can be actively tracked under MRI was developed and tested. The components of the catheter were arranged to form a loopless RF antenna receiver coil that enabled active tracking. Feasibility studies were performed in canine and porcine myocardial infarction models. Myocardial delayed‐enhancement (MDE) imaging identified the infarcted myocardium, and real‐time MRI was used to guide left ventricular catheterization from a carotid artery approach. The distal 35 cm of the catheter was seen under MRI with a bright signal at the distal tip of the catheter. The catheter was steered into position, the distal tip was apposed against the infarct, the needle was advanced, and a bolus of MR contrast agent and tissue marker dye was injected intramyocardially, as confirmed by imaging and postmortem histology. A pilot study involving intramyocardial delivery of magnetically labeled stem cells demonstrated the utility of the active injection catheter system. Magn Reson Med 51:1163–1172, 2004.

Real-Time Magnetic Resonance Imaging–Guided Endovascular Recanalization of Chronic Total Arterial Occlusion in a Swine Model

Background— Endovascular recanalization (guidewire traversal) of peripheral artery chronic total occlusion (CTO) can be challenging. X-ray angiography resolves CTO poorly. Virtually “blind” device advancement during x-ray–guided interventions can lead to procedure failure, perforation, and hemorrhage. Alternatively, MRI may delineate the artery within the occluded segment to enhance procedural safety and success. We hypothesized that real-time MRI (rtMRI)–guided CTO recanalization can be accomplished in an animal model. Methods and Results— Carotid artery CTO was created by balloon injury in 19 lipid-overfed swine. After 6 to 8 weeks, 2 underwent direct necropsy analysis for histology, 3 underwent primary x-ray–guided CTO recanalization attempts, and the remaining 14 underwent rtMRI-guided recanalization attempts in a 1.5-T interventional MRI system. Real-time MRI intervention used custom CTO catheters and guidewires that incorporated MRI receiver antennae to enhance device visibility. The mean length of the occluded segments was 13.3±1.6 cm. The rtMRI-guided CTO recanalization was successful in 11 of 14 swine and in only 1 of 3 swine with the use of x-ray alone. After unsuccessful rtMRI (n=3), x-ray–guided attempts were also unsuccessful. Conclusions— Recanalization of long CTO is entirely feasible with the use of rtMRI guidance. Low-profile clinical-grade devices will be required to translate this experience to humans.

Magnetic resonance image-guided trans-septal puncture in a swine heart

To test the feasibility of performing magnetic resonance (MR)‐guided trans‐septal punctures in the swine heart.

Real-time MRI guided atrial septal puncture and balloon septostomy in swine

Cardiac perforation during atrial septal puncture (ASP) might be avoided by improved image guidance. X‐ray fluoroscopy (XRF), which guides ASP, visualizes tissue poorly and does not convey depth information. Ultrasound is limited by device shadows and constrained imaging windows. Alternatively, real‐time MRI (rtMRI) provides excellent tissue contrast in any orientation and may enable ASP and balloon atrial septostomy (BAS) in swine. Custom MRI catheters incorporated “active” (receiver antenna) and “passive” (iron or gadolinium) elements. Wholly rtMRI‐guided transfemoral ASP and BAS were performed in 10 swine in a 1.5T interventional suite. Hemodynamic results were measured with catheters and velocity encoded MRI. Successful ASP was performed in all 10 animals. Necropsy confirmed septostomy confined within the fossa ovalis in all. BAS was successful in 9/10 animals. Antenna failure in a re‐used needle led to inadvertent vena cava tear prior to BAS in 1 animal. ASP in the same animal was easily performed using a new needle. rtMRI illustrated clear device‐tissue‐lumen relationships in multiple orientations, and facilitated simple ASP and BAS. The mean procedure time was 19 ± 10 minutes. Septostomy achieved a mean left to right shunt ratio of 1.3:1 in these healthy animals. Interactive rtMRI permits rapid transcatheter ASP and BAS in swine. Further technical development may enable novel applications. Published 2006 Wiley‐Liss, Inc.

Interventional cardiovascular procedures guided by real-time MR imaging: An interactive interface using multiple slices, adaptive projection modes and live 3D renderings

To develop and test a novel interactive real‐time MRI environment that facilitates image‐guided cardiovascular interventions.

Minimizing RF heating of conducting wires in MRI

Performing interventions using long conducting wires in MRI introduces the risk of focal RF heating at the wire tip. Comprehensive EM simulations are combined with carefully measured experimental data to show that method‐of‐moments EM field modeling coupled with heat transfer modeling can adequately predict RF heating with wires partially inserted into the patient‐mimicking phantom. The effects of total wire length, inserted length, wire position in the phantom, phantom position in the scanner, and phantom size are examined. Increasing phantom size can shift a wires length of maximum tip heating from about a half wave toward a quarter wave. In any event, with wires parallel to the scanner bore, wire tip heating is minimized by keeping the patient and wires as close as possible to the central axis of the scanner bore. At 1.5T, heating is minimized if bare wires are shorter than 0.6 m or between ≈2.4 m and ≈3.0 m. Heating is further minimized if wire insertion into phantoms equivalent to most aqueous soft tissues is less than 13 cm or greater than 40 cm (longer for fatty tissues, bone, and lung). The methods demonstrated can be used to estimate the absolute amount of heating in order to set RF power safety thresholds. Magn Reson Med 58:1028–1034, 2007.

Development of a 0.014-inch magnetic resonance imaging guidewire

The purpose of this study was to develop a standard 0.014‐inch intravascular magnetic resonance imaging guidewire (MRIG), a coaxial cable with an extension of the inner conductor, specifically designed for use in the small vessels. After a theoretical analysis, the 0.014‐inch MRIG was built by plating/cladding highly electrically conductive materials, silver or gold, over the inside and outside of the coaxial conductors. The conductors were made of superelastic, nonmagnetic, biocompatible materials, Nitinol or MP35N. Then, in comparison with a previously designed 0.032‐inch MRIG, the performance of the new 0.014‐inch MRIG in vitro and in vivo was successfully evaluated. This study represents the initial work to confirm the critical role of highly conductive and superelastic materials in building such small‐size MRIGs, which are expected to generate high‐resolution MR imaging of vessel walls/plaques and guide endovascular interventional procedures in the small vessels, such as the coronary arteries. Magn Reson Med 53:986–990, 2005.

Intracoronary MR imaging using a 0.014-inch MR imaging-guidewire: toward MRI-guided coronary interventions.

To validate the feasibility of using a newly designed MR imaging‐guidewire (MRIG) to guide angioplasty balloon placement in coronary arteries.

Evaluation of MR/Fluoroscopy-guided Portosystemic Shunt Creation in a Swine Model

PURPOSE To evaluate three different percutaneous portosystemic shunts created with magnetic resonance (MR) imaging and fluoroscopy guidance in a swine model. MATERIALS AND METHODS In stage 1 of the experiment, an active MR intravascular needle system was created for needle tracking and extracaval punctures. Twenty inferior vena cava (IVC)/superior mesenteric vein (SMV)/portal vein (PV) punctures were performed in 10 swine (weight, 40-45 kg) in a 1.5-T short-bore interventional MR imager. With use of a real-time MR imaging sequence, the needle was guided through the IVC and into the SMV or PV (N = 20 punctures). After confirmation, a wire was advanced into the portal venous system under MR imaging guidance (N = 20). In stage 2, animals were transferred to the radiographic fluoroscopy suite for deployment of shunts. Three different shunts were evaluated in this study: (i) a commercial stent-graft, (ii) a prototype bridging stent, and (iii) a prototype nitinol vascular anastomotic device. Postprocedural necropsy was performed in all animals. RESULTS Successful MR-guided IVC/SMV punctures were performed in all 20 procedures (100%). All three shunts were deployed. Stent-grafts had the poorest mechanism for securing a shunt. The vascular anastomotic device and the bridging stent had more secure anchoring mechanisms but also had higher technical failure rates (50% and 40%, respectively). When deployed successfully, the vascular anastomotic device resulted in no bleeding at the sites of punctures at necropsy. CONCLUSION Percutaneous shunts and vascular anastomoses between the portal mesenteric venous system and IVC were successfully created with use of a combination of MR imaging and conventional fluoroscopy for guidance.