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 beta-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 beta-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.

Designing passive MRI-safe implantable conducting leads with electrodes.

PURPOSE: The presence of implanted electronic devices with conducting leads and electrodes are contraindicated for magnetic resonance imaging (MRI), denying many patients its potential benefits. The prime concern is MRI's radio frequency (RF) fields, which can cause elevated local specific absorption rates (SARs) and potential heat injury. The purpose of this article is to develop and compare a range of passive implantable "MRI-safe" lead designs. METHODS: Conducting leads incorporating different lengths (3-75 cm), insulation thicknesses (0-105 microm), resistances (100-3000 omega), coiled conductors (inner diameter < or = 1.2 mm), high-impedance (135-2700 omega) RF traps, and single-coiled and triple-coiled coaxial-wound "billabong" leads with reversed coil sections that oppose and reduce the induced current, are investigated both experimentally using local temperature measurements, and by numerical full-wave electromagnetic field analysis of the local SAR, in three different-sized bioanalogous model saline-gel phantoms at 1.5 T MRI and 4 W/kg exposure. RESULTS: In all designs, the maximum computed 1 g average SAR and experimental temperature rise occur at the bare electrodes. Electrode heating increases with lead insulation thickness and peaks for uncoiled leads 25-50 cm long. A reasonable match between computed SAR and the point SAR estimated from thermal sensors obtained by approximating the computation volume to that of the thermal probes. Factors that maximize the impedance of leads with resistive, coiled, RF trap and billabong elements can effectively limit heating below 1-2 degrees, but folded lead configurations can be a concern. The RF trap and billabong designs can both support multiple conductors and electrodes, with billabong prototype leads also heating <1 degrees C when tested for 3 T MRI. CONCLUSIONS: Lead insulation and length strongly affect implanted lead safety to RF exposure during MRI. Lead designs employing impedance and reversed winding sections offer hope for the development of passive, MRI-safe, implantable conducting leads for future human use.

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.

Real-time magnetic resonance-guided endovascular repair of experimental abdominal aortic aneurysm in swine.

OBJECTIVES: This study tested the hypotheses that endografts can be visualized and navigated in vivo solely under real-time magnetic resonance imaging (rtMRI) guidance to repair experimental abdominal aortic aneurysms (AAA) in swine, and that MRI can provide immediate assessment of endograft apposition and aneurysm exclusion. BACKGROUND: Endovascular repair for AAA is limited by endoleak caused by inflow or outflow malapposition. The ability of rtMRI to image soft tissue and flow may improve on X-ray guidance of this procedure. METHODS: Infrarenal AAA was created in swine by balloon overstretch. We used one passive commercial endograft, imaged based on metal-induced MRI artifacts, and several types of homemade active endografts, incorporating MRI receiver coils (antennae). Custom interactive rtMRI features included color coding the catheter-antenna signals individually, simultaneous multislice imaging, and real-time three-dimensional rendering. RESULTS: Eleven repairs were performed solely using rtMRI, simultaneously depicting the device and soft-tissue pathology during endograft deployment. Active devices proved most useful. Intraprocedural MRI provided anatomic confirmation of stent strut apposition and functional corroboration of aneurysm exclusion and restoration of laminar flow in successful cases. In two cases, there was clear evidence of contrast accumulation in the aneurysm sac, denoting endoleak. CONCLUSIONS: Endovascular AAA repair is feasible under rtMRI guidance. Active endografts facilitate device visualization and complement the soft tissue contrast afforded by MRI for precise positioning and deployment. Magnetic resonance imaging also permits immediate post-procedural anatomic and functional evaluation of successful aneurysm exclusion.

Tracking planar orientations of active MRI needles.

PURPOSE: To determine and track the planar orientation of active interventional devices without using localizing RF microcoils. MATERIALS AND METHODS: An image-based tracking method that determines a device's orientation using projection images was developed. An automated and a manual detection scheme were implemented. The method was demonstrated in an in vivo mesocaval puncture procedure in swine, which required accurate orientation of an active transvascular needle catheter. RESULTS: The plane of the catheter was determined using two projection images. The scan plane was adjusted automatically to follow the catheter plane, and its orientation with respect to a previously acquired target plane was displayed. The algorithm facilitated navigation for a fast and accurate puncture. CONCLUSION: Using image-based techniques, with no mechanical design changes, the orientation of an active intravascular probe could be tracked.

Beating heart aortic valve replacement using real-time MRI guidance.

OBJECTIVE: : The principal limitations of percutaneous techniques to replace the aortic valve are detailed visualization and durable prostheses. We report the feasibility of using real-time magnetic resonance imaging (MRI) to provide precise anatomic detail and visual feedback to implant a proven bioprosthesis. METHODS: : Twelve domestic pigs were anesthetized, and, through a minimally invasive approach using real-time MRI guidance, underwent aortic valve replacement. This was accomplished on the beating heart by using a commercially available bioprosthesis. MRI was used to precisely identify the anatomic landmarks of the aortic annulus, coronary artery ostia, and the mitral valve leaflets. Additional intraoperative perfusion, flow velocity, and functional imaging were used to confirm adequacy of placement and function of the valve. RESULTS: : Under real-time MRI, multiple oblique planes were prescribed to delineate the anatomy of the native aortic valve and left ventricular outflow track. Enhanced by the use of an active marker wire, this imaging allowed correct placement and orientation of the valve. Through a transapical approach, a series of bioprosthetic aortic valves (21 to 25 mm) were inserted. The time to implantation after the placement of the trocar to deployment of the valve was less than 90 seconds. The average procedure duration was less than 40 minutes CONCLUSIONS: : Real-time MRI provides excellent anatomic detail and intraoperative assessment that permits placement of durable valve prostheses on the beating heart without the limitations of percutaneous approaches.

Percutaneous MR imaging-guided transvascular access of mesenteric venous system: study in swine model.

PURPOSE: To determine if, with use of magnetic resonance (MR) imaging guidance alone, transcaval puncture of the superior mesenteric vein (SMV) and/or portal vein is feasible with a percutaneous femoral vein approach. MATERIALS AND METHODS: The Institutional Animal Care and Use Committee approved the animal studies. Ten inferior vena cava (IVC)-SMV punctures were performed in six pigs. An active MR intravascular needle system was used for all transvascular punctures, and all procedures were performed with a 1.5-T MR unit. The needle was introduced via a 12-F femoral vein sheath and advanced into the IVC by using a real-time gradient-recalled-echo sequence (3.4/1.2 [repetition time msec/echo time msec], 45 degrees flip angle, and six to eight frames per second). Fast transverse spoiled gradient-recalled acquisition in the steady state (SPGR) (6.0/1.5, 60 degrees flip angle, one frame per second) was performed to confirm needle trajectory. The needle system was advanced under real-time MR imaging to puncture the SMV. The location of the needle tip was confirmed with a fast spin-echo sequence (1904/4.5, 36-cm field of view). A direct MR portogram was obtained after the administration of gadopentetate dimeglumine at a concentration of 25% with fast SPGR (6/1.3, 90 degrees flip angle, no section selection, three frames per second). Success was defined as entry into the mesenteric venous system without traversal of any retroperitoneal organs or adjacent vasculature. RESULTS: Successful MR imaging-guided IVC-SMV punctures were performed in all 10 procedures (100%). The needle was fully visualized as it traversed the retroperitoneum and entered the SMV. MR portograms were successfully obtained following all punctures through the needle. Conventional transverse MR imaging helped confirm that the needle did not traverse any retroperitoneal organs or vessels. CONCLUSION: With use of only MR imaging guidance and an active MR imaging intravascular needle system, the authors were able to successfully puncture the SMV from the IVC with direct visualization of the needle and all retroperitoneal structures.

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.

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.

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

PURPOSE: To test the feasibility of performing magnetic resonance (MR)-guided trans-septal punctures in the swine heart. MATERIALS AND METHODS: All procedures were performed in a 1.5-T MR scanner. A novel, active MR intravascular needle system was utilized for needle tracking and septal punctures. Trans-septal punctures were performed in five swine using electrocardiogram (ECG)-gated high resolution and non-ECG-gated, real-time MR imaging techniques. The intravascular needle was advanced over a guidewire from the femoral vein. Once the needle was in proper position, trans-septal punctures were made. RESULTS: Active tracking of the needle traversing the septum was possible. The location of the catheter tip was confirmed using real time gradient recalled echo (GRE). After a confirmatory ventriculogram with gadolinium-DTPA, a 0.014-inch guidewire was advanced into the left atrium and left ventricle. All punctures were made with no change in cardiac rhythm or rate; postmortem analysis was performed on all animals and demonstrated that 18/19 (95%) punctures were directly through the fossa ovalis. CONCLUSION: Using only MR guidance and a novel active intravascular needle system, we were able to repeatedly puncture the fossa ovalis in a swine heart from a transfemoral approach, with direct visualization of all components, including the needle, the atria, the fossa ovalis, and the surrounding vasculature.