Michael A. Guttman

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 (104 to 106 cells/150 &mgr;L) 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 105 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.

Tag and contour detection in tagged MR images of the left ventricle

Tracking magnetic resonance tags in myocardial tissue promises to be an effective tool for the assessment of myocardial motion. The authors describe a hierarchy of image processing steps which rapidly detects both the contours of the myocardial boundaries of the left ventricle and the tags within the myocardium. The method works on both short axis and long axis images containing radial and parallel tag patterns, respectively. Left ventricular boundaries are detected by first removing the tags using morphological closing and then selecting candidate edge points. The best inner and outer boundaries are found using a dynamic program that minimizes a nonlinear combination of several local cost functions. Tags are tracked by matching a template of their expected profile using a least squares estimate. Since blood pooling, contiguous and adjacent tissue, and motion artifacts sometimes cause detection errors, a graphical user interface was developed to allow user correction of anomalous points. The authors present results on several tagged images of a human. A fully automated run generally finds the endocardial boundary and the tag lines extremely well, requiring very little manual correction. The epicardial boundary sometimes requires more intervention to obtain an acceptable result. These methods are currently being used in the analysis of cardiac strain and as a basis for the analysis of alternate tag geometries.

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 1.7×3.3×8-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.

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.

Analysis of cardiac function from MR images

Recent research and development in cardiac magnetic resonance imaging (MRI) has shown that a single exam, performed entirely in an MR scanner, might well replace the current sequence of tests for coronary disease. Though an MR scanner is expensive, the ability to consolidate diagnostic tests into a single session would significantly reduce costs and increase convenience for the patient. MRI might also provide the physician with diagnostic information on myocardial function that is not available from the standard battery of tests. In this article, we concentrate on one aspect of a cardiac MRI exam that provides previously unavailable information: assessment of myocardial contraction.

Real-Time Interactive MRI-Guided Cardiac Surgery: Aortic Valve Replacement Using a Direct Apical Approach

Minimally invasive cardiac surgery requires arresting and emptying of the heart, which compromises visualization of the surgical field. In this feasibility study a novel surgical procedure is demonstrated in which real‐time MRI is used to guide the placement of a prosthetic aortic valve in the beating heart via direct apical access in eight porcine hearts. A clinical stentless bioprosthetic valve affixed to a platinum stent was compressed onto a balloon‐tipped catheter. This was fed through a 15–18‐mm delivery port inserted into the left ventricular (LV) apex via a minimally invasive subxyphoid incision. Using interactive real‐time MRI, the surgeon implanted the prosthetic valve in the correct location at the aortic annulus within 90 s. In four of the animals immediately after implantation, ventricular function, blood flow through the valve, and myocardial perfusion were evaluated with MRI. MRI‐guided beating‐heart surgery may provide patients with a less morbid and more durable solution to structural heart disease. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.

Real‐time accelerated interactive MRI with adaptive TSENSE and UNFOLD

Reduced field‐of‐view (FOV) acceleration using time‐adaptive sensitivity encoding (TSENSE) or unaliasing by Fourier encoding the overlaps using the temporal dimension (UNFOLD) can improve the depiction of motion in real‐time MRI. However, increased computational resources are required to maintain a high frame rate and low latency in image reconstruction and display. A high‐performance software system has been implemented to perform TSENSE and UNFOLD reconstructions for real‐time MRI with interactive, on‐line display. Images were displayed in the scanner room to investigate image‐guided procedures. Examples are shown for normal volunteers and cardiac interventional experiments in animals using a steady‐state free precession (SSFP) sequence. In order to maintain adequate image quality for interventional procedures, the imaging rate was limited to seven frames per second after an acceleration factor of 2 with a voxel size of 1.8 × 3.5 × 8 mm. Initial experiences suggest that TSENSE and UNFOLD can each improve the compromise between spatial and temporal resolution in real‐time imaging, and can function well in interactive imaging. UNFOLD places no additional constraints on receiver coils, and is therefore more flexible than SENSE methods; however, the temporal image filtering can blur motion and reduce the effective acceleration. Methods are proposed to overcome the challenges presented by the use of TSENSE in interactive imaging. TSENSE may be temporarily disabled after changing the imaging plane to avoid transient artifacts as the sensitivity coefficients adapt. For imaging with a combination of surface and interventional coils, a hybrid reconstruction approach is proposed whereby UNFOLD is used for the interventional coils, and TSENSE with or without UNFOLD is used for the surface coils. Magn Reson Med 50:315–321, 2003. Published 2003 Wiley‐Liss, Inc.

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.

Novel technique for cardiac electromechanical mapping with magnetic resonance imaging tagging and an epicardial electrode sock.

AbstractNear-simultaneous measurements of electrical and mechanical activation over the entire ventricular surface are now possible using magnetic resonance imaging tagging and a multielectrode epicardial sock. This new electromechanical mapping technique is demonstrated in the ventricularly paced canine heart. A 128–electrode epicardial sock and pacing electrodes were placed on the hearts of four anesthetized dogs. In the magnetic resonance scanner, tagged cine images (8–15 ms/frame) and sock electrode recordings (1000 Hz) were acquired under right-ventricular pacing and temporally referenced to the pacing stimulus. Electrical recordings were obtained during intermittent breaks in image acquisition, so that both data sets represented the same physiologic state. Since the electrodes were not visible in the images, electrode recordings and cine images were spatially registered with Gd-DTPA markers attached to the sock. Circumferential strain was calculated at locations corresponding to electrodes. For each electrode location, electrical and mechanical activation times were calculated and relationships between the two activation patterns were demonstrated. This method holds promise for improving understanding of the relationships between the patterns of electrical activation and contraction in the heart.

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.