The Relationship between MRI Radiofrequency Energy and Function of Nonconditional Implanted Cardiac Devices: A Prospective Evaluation.

Background The risks associated with MRI in individuals who have implanted cardiac devices are thought to arise from the interaction between the implanted device and static, gradient, and radiofrequency magnetic fields. Purpose To determine the relationship between the peak whole-body averaged specific absorption rate (SAR) and change in magnetic field per unit time (dB/dt), maximum specific energy dose, imaging region, and implanted cardiac device characteristics and their function in patients undergoing MRI. Materials and Methods This prospective observational cohort study was conducted from October 16, 2003, to January 22, 2015 (https://ClinicalTrials.gov, NCT01130896). Any individual with an implanted cardiac device who was referred for MRI was included. Clinical MRI protocols without SAR restriction were used. Exclusion criteria were newly implanted leads, abandoned or epicardial leads, and dependence on a pacemaker with an implantable cardioverter defibrillator without asynchronous pacing capability. For each MRI pulse sequence, the calculated whole-body values for SAR, dB/dt, and scan duration were collected. Atrial and ventricular sensing, lead impedance, and capture threshold were evaluated before and immediately after (within 10 minutes) completion of each MRI examination. Generalized estimating equations with Gaussian family, identity link, and an exchangeable working correlation matrix were used for statistical analysis. Results A total of 2028 MRI examinations were performed in 1464 study participants with 2755 device leads (mean age, 67 years ± 15 [standard deviation]; 930 men [64%]). There was no evidence of an association between radiofrequency energy deposition, dB/dt, or scan duration and changes in device parameters. Thoracic MRI was associated with decreased battery voltage immediately after MRI (ß = -0.008 V, P < .001). Additionally, right ventricular (RV) lead length was associated with decreased RV sensing (ß = -0.012 mV, P = .05) and reduced RV capture threshold (ß = -0.002 V, P < .01) immediately after MRI. Conclusion There was no evidence of an association between MRI parameters that characterize patient exposure to radiofrequency energy and changes in device and lead parameters immediately after MRI. Nevertheless, device interrogation before and after MRI remains mandatory due to the potential for device reset and changes in lead or generator parameters. © RSNA, 2020 See also the editorial by Shellock in this issue.

Acute enhancement of necrotic radio-frequency ablation lesions in left atrium and pulmonary vein ostia in swine model with non-contrast-enhanced T1 -weighted MRI.

PURPOSE: To evaluate non-contrast-enhanced MRI of acute radio-frequency ablation (RFA) lesions in the left atrium (LA) and pulmonary vein (PV) ostia. The goal is to provide a method for discrimination between necrotic (permanent) lesions and reversible injury, which is associated with recurrence after treatment of atrial fibrillation. METHODS: Fifteen normal swine underwent RFA around the right-superior PV ostia. Electrical pulmonary vein isolation (PVI) was verified by electro-anatomic mapping (EAM) and pacing. MRI was carried out using a 3D respiratory-gated T1 -weighted long inversion time (TWILITE) sequence without contrast agent. Key settings were: inversion time 700 ms, triggering over 2 cardiac cycles, pixel size 1.1 mm3 . Contrast-enhanced imaging and T2 -weighted imaging were carried out for comparison. Six animals were sacrificed on ablation day for TTC-stained gross pathology, 9 animals were sacrificed after 2-3 mo after repeat EAM and MRI. Image intensity ratio (IIR) was used to measure lesion enhancement, and gross pathology was used to validate image enhancement patterns and compare lesion widths. RESULTS: RFA lesions exhibited unambiguous enhancement in acute TWILITE imaging (IIR = 2.34 ± 0.49 at 1.5T), and the enhancement patterns corresponded well with gross pathology. Lesion widths in MRI correlated well with gross pathology (R2 = 0.84), with slight underestimation by 0.9 ± 0.5 mm. Lesion enhancement subsided chronically. CONCLUSION: TWILITE imaging allowed acute detection of permanent RFA lesions in swine LA and PV ostia, without the need for contrast agent. Lesion enhancement pattern showed good correspondence to gross pathology and was well visualized by volume rendering. This method may provide valuable intra- or post-procedural assessment of RFA treatment.

Non-contrast-enhanced T1 -weighted MRI of myocardial radiofrequency ablation lesions.

PURPOSE: To demonstrate imaging of radiofrequency ablation lesions with non-contrast-enhanced T1 -weighted (T1w) MRI. METHODS: Fifteen swine underwent left ventricular ablation followed by MRI using different preparations: endocardial or epicardial ablation of naïve animal, or endocardial ablation of animal with myocardial infarction. Lesion imaging was performed using free-breathing, non-contrast-enhanced, T1w sequence with long inversion time (TI). Also acquired were T1 maps and delayed contrast-enhanced (DCE) imaging. Hearts were excised for ex vivo imaging, and sliced for gross pathology and histology. RESULTS: All ablations were visibly enhanced in non-contrast-enhanced T1w imaging using TI = 700 ms. T1w enhancement agreed with regions of necrosis in gross pathology and histology. Enhanced lesion cores were surrounded by dark bands containing contraction band necrosis, hematoma, and edema. In animals with myocardial infarction, chronic scar was hypointense in T1w, whereas acute ablations were enhanced, allowing discrimination between chronic scar and acute lesions, unlike DCE. Contrast was sufficient to create 3D volume renderings of lesions after minor postprocessing. CONCLUSIONS: Non-contrast-enhanced T1w imaging with long TI promises to be an effective method for visualizing necrosis within radiofrequency ablation lesions. Enhancement is more specific and stationary than that from DCE. The imaging can be repeated as needed, unlike DCE, and may be especially useful for assessing ablations during or after a procedure. Magn Reson Med 79:879-889, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Rectus femoris knee muscle moment arms measured in vivo during dynamic motion with real-time magnetic resonance imaging.

Moment arms represent a muscle's ability to generate a moment about a joint for a given muscle force. The goal of this study was to develop a method to measure muscle moment arms in vivo over a large range of motion using real-time magnetic resonance (MR) imaging. Rectus femoris muscle-tendon lengths and knee joint angles of healthy subjects (N = 4) were measured during dynamic knee joint flexion and extension in a large-bore magnetic resonance imaging (MRI) scanner. Muscle-tendon moment arms were determined at the knee using the tendon-excursion method by differentiating measured muscle-tendon length with respect to joint angle. Rectus femoris moment arms were averaged across a group of healthy subjects and were found to vary similarly during knee joint flexion (mean: 3.0 (SD 0.5) cm, maximum: 3.5 cm) and extension (mean: 2.8 (SD 0.4) cm, maximum: 3.6 cm). These moment arms compare favorably with previously published dynamic tendon-excursion measurements in cadaveric specimens but were relatively smaller than moment arms from center-of-rotation studies. The method presented here provides a new approach to measure muscle-tendon moment arms in vivo and has the potential to be a powerful resource for characterizing musculoskeletal geometry during dynamic joint motion.

Visualization of active devices and automatic slice repositioning ("SnapTo") for MRI-guided interventions.

The accurate visualization of interventional devices is crucial for the safety and effectiveness of MRI-guided interventional procedures. In this paper, we introduce an improvement to the visualization of active devices. The key component is a fast, robust method ("CurveFind") that reconstructs the three-dimensional trajectory of the device from projection images in a fraction of a second. CurveFind is an iterative prediction-correction algorithm that acts on a product of orthogonal projection images. By varying step size and search direction, it is robust to signal inhomogeneities. At the touch of a key, the imaged slice is repositioned to contain the relevant section of the device ("SnapTo"), the curve of the device is plotted in a three-dimensional display, and the point on a target slice, which the device will intersect, is displayed. These features have been incorporated into a real-time MRI system. Experiments in vitro and in vivo (in a pig) have produced successful results using a variety of single- and multichannel devices designed to produce both spatially continuous and discrete signals. CurveFind is typically able to reconstruct the device curve, with an average error of approximately 2 mm, even in the case of complex geometries.

Interventional MRI using multiple 3D angiography roadmaps with real-time imaging.

PURPOSE: To enhance real-time magnetic resonance (MR)-guided catheter navigation by overlaying colorized multiphase MR angiography (MRA) and cholangiopancreatography (MRCP) roadmaps in an anatomic context. MATERIALS AND METHODS: Time-resolved MRA and respiratory-gated MRCP were acquired prior to real-time imaging in a pig model. MRA and MRCP data were loaded into a custom real-time MRI reconstruction and visualization workstation where they were displayed as maximum intensity projections (MIPs) in distinct colors. The MIPs were rendered in 3D together with real-time multislice imaging data using alpha blending. Interactive rotation allowed different views of the combined data. RESULTS: Fused display of the previously acquired MIP angiography data with real-time imaging added anatomical context during endovascular interventions in swine. The use of multiple MIPs rendered in different colors facilitated differentiation of vascular structures, improving visual feedback during device navigation. CONCLUSION: Interventional real-time MRI may be enhanced by combining with previously acquired multiphase angiograms. Rendered as 3D MIPs together with 2D slice data, this technique provided useful anatomical context that enhanced MRI-guided interventional applications.

HTGRAPPA: real-time B1-weighted image domain TGRAPPA reconstruction.

The temporal generalized autocalibrating partially parallel acquisitions (TGRAPPA) algorithm for parallel MRI was modified for real-time low latency imaging in interventional procedures using image domain, B(1)-weighted reconstruction. GRAPPA coefficients were calculated in k-space, but applied in the image domain after appropriate transformation. Convolution-like operations in k-space were thus avoided, resulting in improved reconstruction speed. Image domain GRAPPA weights were combined into composite unmixing coefficients using adaptive B(1)-map estimates and optimal noise weighting. Images were reconstructed by pixel-by-pixel multiplication in the image domain, rather than time-consuming convolution operations in k-space. Reconstruction and weight-set calculation computations were parallelized and implemented on a general-purpose multicore architecture. The weight calculation was performed asynchronously to the real-time image reconstruction using a dedicated parallel processing thread. The weight-set coefficients were computed in an adaptive manner with updates linked to changes in the imaging scan plane. In this implementation, reconstruction speed is not dependent on acceleration rate or GRAPPA kernel size.

Whole shaft visibility and mechanical performance for active MR catheters using copper-nitinol braided polymer tubes.

BACKGROUND: Catheter visualization and tracking remains a challenge in interventional MR.Active guidewires can be made conspicuous in "profile" along their whole shaft exploiting metallic core wire and hypotube components that are intrinsic to their mechanical performance. Polymer-based catheters, on the other hand, offer no conductive medium to carry radio frequency waves. We developed a new "active" catheter design for interventional MR with mechanical performance resembling braided X-ray devices. Our 75 cm long hybrid catheter shaft incorporates a wire lattice in a polymer matrix, and contains three distal loop coils in a flexible and torquable 7Fr device. We explored the impact of braid material designs on radiofrequency and mechanical performance. RESULTS: The incorporation of copper wire into in a superelastic nitinol braided loopless antenna allowed good visualization of the whole shaft (70 cm) in vitro and in vivo in swine during real-time MR with 1.5 T scanner. Additional distal tip coils enhanced tip visibility. Increasing the copper:nitinol ratio in braiding configurations improved flexibility at the expense of torquability. We found a 16-wire braid of 1:1 copper:nitinol to have the optimum balance of mechanical (trackability, flexibility, torquability) and antenna (signal attenuation) properties. With this configuration, the temperature increase remained less than 2 degrees C during real-time MR within 10 cm horizontal from the isocenter. The design was conspicuous in vitro and in vivo. CONCLUSION: We have engineered a new loopless antenna configuration that imparts interventional MR catheters with satisfactory mechanical and imaging characteristics. This compact loopless antenna design can be generalized to visualize the whole shaft of any general-purpose polymer catheter to perform safe interventional procedures.

Applications of a deep learning method for anti-aliasing and super-resolution in MRI.

Magnetic resonance (MR) images with both high resolutions and high signal-to-noise ratios (SNRs) are desired in many clinical and research applications. However, acquiring such images takes a long time, which is both costly and susceptible to motion artifacts. Acquiring MR images with good in-plane resolution and poor through-plane resolution is a common strategy that saves imaging time, preserves SNR, and provides one viewpoint with good resolution in two directions. Unfortunately, this strategy also creates orthogonal viewpoints that have poor resolution in one direction and, for 2D MR acquisition protocols, also creates aliasing artifacts. A deep learning approach called SMORE that carries out both anti-aliasing and super-resolution on these types of acquisitions using no external atlas or exemplars has been previously reported but not extensively validated. This paper reviews the SMORE algorithm and then demonstrates its performance in four applications with the goal to demonstrate its potential for use in both research and clinical scenarios. It is first shown to improve the visualization of brain white matter lesions in FLAIR images acquired from multiple sclerosis patients. Then it is shown to improve the visualization of scarring in cardiac left ventricular remodeling after myocardial infarction. Third, its performance on multi-view images of the tongue is demonstrated and finally it is shown to improve performance in parcellation of the brain ventricular system. Both visual and selected quantitative metrics of resolution enhancement are demonstrated.

Ablation Lesion Characterization in Scarred Substrate Assessed Using Cardiac Magnetic Resonance.

OBJECTIVES: This study examined radiofrequency catheter ablation (RFCA) lesions within and around scar by cardiac magnetic resonance (CMR) imaging and histology. BACKGROUND: Substrate modification by RFCA is the cornerstone therapy for ventricular arrhythmias. RFCA in scarred myocardium, however, is not well understood. METHODS: We performed electroanatomic mapping and RFCA in the left ventricles of 8 swine with myocardial infarction. Non-contrast-enhanced T1-weighted (T1w) and contrast-enhanced CMR after RFCA were compared with gross pathology and histology. RESULTS: Of 59 lesions, 17 were in normal myocardium (voltage >1.5 mV), 21 in border zone (0.5 to 1.5 mV), and 21 in scar (<0.5 mV). All RFCA lesions were enhanced in T1w CMR, whereas scar was hypointense, allowing discrimination among normal myocardium, scar, and RFCA lesions. With contrast-enhancement, lesions and scar were similarly enhanced and not distinguishable. Lesion width and depth in T1w CMR correlated with necrosis in pathology (both; r2 = 0.94, p < 0.001). CMR lesion volume was significantly different in normal myocardium, border zone, and scar (median: 397 [interquartile range (IQR): 301 to 474] mm3, 121 [IQR: 87 to 201] mm3, 66 [IQR: 33 to 123] mm3, respectively). RFCA force-time integral, impedance, and voltage changes did not correlate with lesion volume in border zone or scar. Histology showed that ablation necrosis extended into fibrotic tissue in 26 lesions and beyond in 14 lesions. In 7 lesions, necrosis expansion was blocked and redirected by fat. CONCLUSIONS: T1w CMR can selectively enhance necrotic tissue in and around scar and may allow determination of the completeness of ablation intra- and post-procedure. Lesion formation in scar is affected by tissue characteristics, with fibrosis and fat acting as thermal insulators.

Real-time MR imaging-guided laser atrial septal puncture in swine.

PURPOSE: The authors performed this study to report their initial preclinical experience with real-time magnetic resonance (MR) imaging-guided atrial septal puncture by using a MR imaging-conspicuous blunt laser catheter that perforates only when energized. MATERIALS AND METHODS: The authors customized a 0.9-mm clinical excimer laser catheter with a receiver coil to impart MR imaging visibility at 1.5 T. Seven swine underwent laser transseptal puncture under real-time MR imaging. MR imaging signal-to-noise ratio profiles of the device were obtained in vitro. Tissue traversal force was tested with a calibrated meter. Position was corroborated with pressure measurements, oximetry, angiography, and necropsy. Intentional non-target perforation simulated serious complication. RESULTS: Embedded MR imaging antennae accurately reflected the position of the laser catheter tip and profile in vitro and in vivo. Despite having an increased profile from the microcoil, the 0.9-mm laser catheter traversed in vitro targets with similar force (0.22 N +/- 0.03) compared with the unmodified laser. Laser puncture of the atrial septum was successful and accurate in all animals. The laser was activated an average of 3.8 seconds +/- 0.4 before traversal. There were no sequelae after 6 hours of observation. Necropsy revealed 0.9-mm holes in the fossa ovalis in all animals. Intentional perforation of the aorta and atrial free wall was evident immediately. CONCLUSIONS: MR imaging-guided laser puncture of the interatrial septum is feasible in swine and offers controlled delivery of perforation energy by using an otherwise blunt catheter. Instantaneous soft tissue imaging provides immediate feedback on safety.

Interventional cardiovascular magnetic resonance: still tantalizing.

The often touted advantages of MR guidance remain largely unrealized for cardiovascular interventional procedures in patients. Many procedures have been simulated in animal models. We argue these opportunities for clinical interventional MR will be met in the near future. This paper reviews technical and clinical considerations and offers advice on how to implement a clinical-grade interventional cardiovascular MR (iCMR) laboratory. We caution that this reflects our personal view of the "state of the art."

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 imaging guidance for cardiovascular procedures.

Magnetic resonance imaging (MRI) of the cardiovascular system has proven to be an invaluable diagnostic tool. Given the ability to allow for real-time imaging, MRI guidance of intraoperative procedures can provide superb visualization, which can facilitate a variety of interventions and minimize the trauma of the operations as well. In addition to the anatomic detail, MRI can provide intraoperative assessment of organ and device function. Instruments and devices can be marked to enhance visualization and tracking, all of which is an advance over standard X-ray or ultrasonic imaging.

Real-time magnetic resonance imaging-guided stenting of aortic coarctation with commercially available catheter devices in Swine.

BACKGROUND: Real-time MR imaging (rtMRI) is now technically capable of guiding catheter-based cardiovascular interventions. Compared with x-ray, rtMRI offers superior tissue imaging in any orientation without ionizing radiation. Translation to clinical trials has awaited the availability of clinical-grade catheter devices that are both MRI visible and safe. We report a preclinical safety and feasibility study of rtMRI-guided stenting in a porcine model of aortic coarctation using only commercially available catheter devices. METHOD AND RESULTS: Coarctation stenting was performed wholly under rtMRI guidance in 13 swine. rtMRI permitted procedure planning, device tracking, and accurate stent deployment. "Active" guidewires, incorporating MRI antennas, improved device visualization compared with unmodified "passive" nitinol guidewires and shortened procedure time (26+/-11 versus 106+/-42 minutes; P=0.008). Follow-up catheterization and necropsy showed accurate stent deployment, durable gradient reduction, and appropriate neointimal formation. MRI immediately identified aortic rupture when oversized devices were tested. CONCLUSIONS: This experience demonstrates preclinical safety and feasibility of rtMRI-guided aortic coarctation stenting using commercially available catheter devices. Patients may benefit from rtMRI in the future because of combined device and tissue imaging, freedom from ionizing radiation, and the ability to identify serious complications promptly.

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.

A Magnetic Resonance Imaging-Conditional External Cardiac Defibrillator for Resuscitation Within the Magnetic Resonance Imaging Scanner Bore.

BACKGROUND: Subjects undergoing cardiac arrest within a magnetic resonance imaging (MRI) scanner are currently removed from the bore and then from the MRI suite, before the delivery of cardiopulmonary resuscitation and defibrillation, potentially increasing the risk of mortality. This precludes many higher-risk (acute ischemic and acute stroke) patients from undergoing MRI and MRI-guided intervention. An MRI-conditional cardiac defibrillator should enable scanning with defibrillation pads attached and the generator ON, enabling application of defibrillation within the seconds of MRI after a cardiac event. An MRI-conditional external defibrillator may improve patient acceptance for MRI procedures. METHODS AND RESULTS: A commercial external defibrillator was rendered 1.5 Tesla MRI-conditional by the addition of novel radiofrequency filters between the generator and commercial disposable surface pads. The radiofrequency filters reduced emission into the MRI scanner and prevented cable/surface pad heating during imaging, while preserving all the defibrillator monitoring and delivery functions. Human volunteers were imaged using high specific absorption rate sequences to validate MRI image quality and lack of heating. Swine were electrically fibrillated (n=4) and thereafter defibrillated both outside and inside the MRI bore. MRI image quality was reduced by 0.8 or 1.6 dB, with the generator in monitoring mode and operating on battery or AC power, respectively. Commercial surface pads did not create artifacts deeper than 6 mm below the skin surface. Radiofrequency heating was within US Food and Drug Administration guidelines. Defibrillation was completely successful inside and outside the MRI bore. CONCLUSIONS: A prototype MRI-conditional defibrillation system successfully defibrillated in the MRI without degrading the image quality or increasing the time needed for defibrillation. It can increase patient acceptance for MRI procedures.

Catheter-based endomyocardial injection with real-time magnetic resonance imaging.

BACKGROUND: We tested the feasibility of targeted left ventricular (LV) mural injection using real-time MRI (rtMRI). METHODS AND RESULTS: A 1.5T MRI scanner was customized with a fast reconstruction engine, transfemoral guiding catheter-receiver coil (GCC), MRI-compatible needle, and tableside consoles. Commercial real-time imaging software was customized to facilitate catheter navigation and visualization of injections at 4 completely refreshed frames per second. The aorta was traversed and the left ventricular cavity was entered under direct rtMRI guidance. Pigs underwent multiple injections with dilute gadolinium-DTPA. All myocardial segments were readily accessed. The active GCC and the passive Stiletto needle injector were readily visualized. More than 50 endomyocardial injections were performed with the aid of rtMRI; 81% were successful with this first-generation prototype. CONCLUSION: Percutaneous endomyocardial drug delivery is feasible with the aid of rtMRI, which permits precise 3-dimensional localization of injection within the LV wall.

Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in Swine.

BACKGROUND: The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype. MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately. METHODS AND RESULTS: A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7x3.3x8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem. CONCLUSIONS: Precise targeted delivery of potentially regenerative cellular treatments to recent myocardial infarction borders is feasible with an MR catheter delivery system. MR fluoroscopy permits visualization of catheter navigation, myocardial function, infarct borders, and labeled cells after injection.

Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells.

BACKGROUND: Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization. METHODS AND RESULTS: MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (10(4) to 10(6) cells/150 microL) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI (1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 10(5) MSCs could be detected and contained intact IFP-bearing MSCs on histology. CONCLUSIONS: IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium. The dual-labeled MSCs can be identified at locations corresponding to injection sites, both ex vivo using fluorescence microscopy and in vivo using susceptibility contrast on MRI. This technology may permit effective in vivo study of stem cell retention, engraftment, and migration.