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1.  Bright Blood T2-Weighted MRI Has High Diagnostic Accuracy for Myocardial Hemorrhage in Myocardial Infarction: A Preclinical Validation Study in Swine 
Myocardial hemorrhage after myocardial infarction (MI) usually goes undetected. We investigated the diagnostic accuracy of bright blood T2-weighted cardiac magnetic resonance imaging (MRI) for myocardial hemorrhage in experimental MI.
Methods and Results
MI was created in swine by occluding the left anterior descending (n=10) or circumflex (n=5) coronary arteries for 90 minutes followed by reperfusion for ≤3 days (n=2), 10 days (n=7) or 60 days (n=6). MRI was performed at 1.5 Tesla using bright blood T2-prepared steady-state free-precession, T2* and early (1 min) and late (10 – 15 min) gadolinium enhancement (EGE, LGE, respectively) MRI. Left ventricular sections and histology were assessed for hemorrhage by an experienced cardiac pathologist blinded to the MRI data. Hypointense regions on T2-weighted and contrast-enhanced MRI were independently determined by 3 cardiologists experienced in MRI who were also blinded to the pathology results. Eighty ventricular pathologic sections were matched with MRI (n=68 for EGE MRI). All sections with evidence of MI (n=63 (79%)) also exhibited hyperintense zones consistent with edema on T2-weighted MRI and infarct on LGE MRI. Myocardial hemorrhage occurred in 49 left ventricular sections (61%) and corresponded with signal voids on 48 T2-weighted (98%) and 26 LGE-MRI (53%). Alternatively, signal voids occurred in the absence of hemorrhage in 3 T2-weighted (90% specificity) and 5 LGE MRI (84% specificity). On EGE MRI, 27/43 cases of early MVO corresponded with hemorrhage (63% sensitivity) while 5/25 defects occurred in the absence of hemorrhage (80% specificity). The positive and negative predictive values for pathological evidence of hemorrhage were 94% & 96% for T2-weighted, 84% & 55% for LGE MRI and 85% & 56% for EGE MRI.
Bright blood T2-weighted MRI has high diagnostic accuracy for myocardial hemorrhage.
PMCID: PMC4158314  PMID: 21930836
myocardial infarction; magnetic resonance imaging; hemorrhage
2.  Real-time MRI-guided right heart catheterization in adults using passive catheters 
European Heart Journal  2012;34(5):380-389.
Real-time MRI creates images with superb tissue contrast that may enable radiation-free catheterization. Simple procedures are the first step towards novel interventional procedures. We aim to perform comprehensive transfemoral diagnostic right heart catheterization in an unselected cohort of patients entirely using MRI guidance.
Methods and results
We performed X-ray and MRI-guided transfemoral right heart catheterization in consecutive patients undergoing clinical cardiac catheterization. We sampled both cavae and both pulmonary arteries. We compared success rate, time to perform key steps, and catheter visibility among X-ray and MRI procedures using air-filled or gadolinium-filled balloon-tipped catheters. Sixteen subjects (four with shunt, nine with coronary artery disease, three with other) underwent paired X-ray and MRI catheterization. Complete guidewire-free catheterization was possible in 15 of 16 under both. MRI using gadolinium-filled balloons was at least as successful as X-ray in all procedure steps, more successful than MRI using air-filled balloons, and better than both in entering the left pulmonary artery. Total catheterization time and individual procedure steps required approximately the same amount of time irrespective of image guidance modality. Catheter conspicuity was best under X-ray and next-best using gadolinium-filled MRI balloons.
In this early experience, comprehensive transfemoral right heart catheterization appears feasible using only MRI for imaging guidance. Gadolinium-filled balloon catheters were more conspicuous than air-filled ones. Further workflow and device enhancement are necessary for clinical adoption.
PMCID: PMC3561614  PMID: 22855740
Catheterization; Magnetic resonance imaging; Interventional cardiovascular MRI; Pulmonary artery
3.  Real-time cardiovascular magnetic resonance subxiphoid pericardial access and pericardiocentesis using off-the-shelf devices in swine 
Needle access or drainage of pericardial effusion, especially when small, entails risk of bystander tissue injury or operator uncertainty about proposed trajectories. Cardiovascular magnetic resonance (CMR) might allow enhanced imaging guidance.
Methods and results
We used real-time CMR to guide subxiphoid pericardial access in naïve swine using commercial 18G titanium puncture needles, which were exchanged for pericardial catheters. To test the value of CMR needle pericardiocentesis, we also created intentional pericardial effusions of a range of volumes, via a separate transvenous-transatrial catheter. We performed these procedures in 12 animals.
Pericardiocentesis was performed in 2:47 ± 1:43 minutes; pericardial access was performed in 1:40 ± 4:34 minutes. The procedure was successful in all animals. Moderate and large effusions required only one needle pass. There were no complications, including pleural, hepatic or myocardial transit.
CMR guided pericardiocentesis is attractive because the large field of view and soft tissue imaging depict global anatomic context in arbitrary planes, and allow the operator to plan trajectories that limit inadvertent bystander tissue injury. More important, CMR provides continuous visualization of the needle and target throughout the procedure. Using even passive needle devices, CMR enabled rapid pericardial needle access and drainage. We believe this experience supports clinical testing of real-time CMR guided needle access or drainage of the pericardial space. We suspect this would be especially helpful in “difficult” pericardial access, for example, in distorted thoracic anatomy or loculated effusion.
PMCID: PMC3733815  PMID: 23870697
Pericardiocentesis; Catheterization; Image guided intervention; Interventional magnetic resonance imaging; Cardiovascular magnetic resonance; Pericardial disease
4.  Closed-Chest Transthoracic Magnetic Resonance Imaging-Guided Ventricular Septal Defect Closure in Swine 
JACC. Cardiovascular interventions  2011;4(12):1326-1334.
The aim of this study was to close ventricular septal defects (VSDs) directly through the chest wall using magnetic resonance imaging (MRI) guidance, without cardiopulmonary bypass, sternotomy, or radiation exposure.
Surgical, percutaneous, and hybrid management of VSD each have limitations and known morbidity.
Percutaneous muscular VSDs were created in 10 naive Yorkshire swine using a transjugular laser catheter. Under real-time MRI guidance, a direct transthoracic vascular access sheath was introduced through the chest into the heart along a trajectory suitable for VSD access and closure. Through this transthoracic sheath, muscular VSDs were occluded using a commercial nitinol device. Finally, the right ventricular free wall was closed using a commercial collagen plug intended for arterial closure.
Anterior, posterior, and mid-muscular VSDs (6.8 ± 1.8 mm) were created. VSDs were closed successfully in all animals. The transthoracic access sheath was displaced in 2, both fatal. Thereafter, we tested an intracameral retention sheath to prevent this complication. Right ventricular access ports were closed successfully in all, and after as many as 30 days, healed successfully.
Real-time MRI guidance allowed closed-chest transthoracic perventricular muscular VSD closure in a clinically meaningful animal model. Once applied to patients, this approach may avoid traditional surgical, percutaneous, or open-chest transcatheter (“hybrid”) risks.
PMCID: PMC3670769  PMID: 22192373
hybrid surgical procedures; imaging in the catheterization laboratory; interventional cardiology; interventional MRI; perventricular; ventriculoseptal defect
5.  Transthoracic delivery of large devices into the left ventricle through the right ventricle and interventricular septum: preclinical feasibility 
We aim to deliver large appliances into the left ventricle through the right ventricle and across the interventricular septum. This transthoracic access route exploits immediate recoil of the septum, and lower transmyocardial pressure gradient across the right versus left ventricular free wall. The route may enhance safety and allow subxiphoid rather than intercostal traversal.
The entire procedure was performed under real-time CMR guidance. An “active” CMR needle crossed the chest, right ventricular free wall, and then the interventricular septum to deliver a guidewire then used to deliver an 18Fr introducer. Afterwards, the right ventricular free wall was closed with a nitinol occluder. Immediate closure and late healing of the unrepaired septum and free wall were assessed by oximetry, angiography, CMR, and necropsy up to four weeks afterwards.
The procedure was successful in 9 of 11 pigs. One failed because of refractory ventricular fibrillation upon needle entry, and the other because of inadequate guidewire support. In all ten attempts, the right ventricular free wall was closed without hemopericardium. There was neither immediate nor late shunt on oximetry, X-ray angiography, or CMR. The interventricular septal tract fibrosed completely. Transventricular trajectories planned on human CT scans suggest comparable intracavitary working space and less acute entry angles than a conventional atrial transseptal approach.
Large closed-chest access ports can be introduced across the right ventricular free wall and interventricular septum into the left ventricle. The septum recoils immediately and heals completely without repair. A nitinol occluder immediately seals the right ventricular wall. The entry angle is more favorable to introduce, for example, prosthetic mitral valves than a conventional atrial transseptal approach.
PMCID: PMC4174899  PMID: 23331459
Catheterization; Interventional cardiovascular MR; Structural heart disease
6.  Mitral cerclage annuloplasty, a novel transcatheter treatment for secondary mitral valve regurgitation: Initial results in swine 
Structured Abstract
We developed and tested a novel transcatheter circumferential annuloplasty technique to reduce mitral regurgitation in porcine ischemic cardiomyopathy.
Catheter-based annuloplasty for secondary mitral regurgitation exploits the proximity of the coronary sinus to the mitral annulus, but is limited by anatomic variants and coronary artery entrapment.
The procedure, “cerclage annuloplasty,” is guided by MRI roadmaps fused with live X-ray. A coronary sinus guidewire traverses a short segment of basal septal myocardium to reenter the right heart where it is exchanged for a suture. Tension is applied interactively during imaging and secured with a locking device.
We found two feasible suture pathways from the great cardiac vein across the interventricular septum to create cerclage. Right-ventricular septal reentry required shorter fluoroscopy times than right atrial reentry, which entailed a longer intramyocardial traversal but did not cross the tricuspid valve. Graded tension progressively reduced septal-lateral annular diameter but not end-systolic elastance or regional myocardial function. A simple arch-like device protected entrapped coronary arteries from compression even during supra-therapeutic tension.
Cerclage reduced mitral regurgitation fraction (from 22.8 ± 12.7% to 7.2 ± 4.4%, p=0.04) by slice-tracking velocity-encoded MRI. Flexible cerclage reduced annular size but preserved annular motion. Cerclage also displaced the posterior annulus towards the papillary muscles. Cerclage introduced reciprocal constraint to the left ventricular outflow tract and mitral annulus that enhanced leaflet coaptation.
A sample of human coronary venograms and CT angiograms suggested that most have suitable venous anatomy for cerclage.
Transcatheter mitral cerclage annuloplasty acutely reduces mitral regurgitation in porcine ischemic cardiomyopathy. Entrapped coronary arteries can be protected. MRI provided insight into the mechanism of cerclage action.
PMCID: PMC3034128  PMID: 19660696
Image guided intervention; Catheter-based intervention, non-coronary; Magnetic resonance imaging; Multimodality image fusion
7.  Real-Time MRI Guided Laser Atrial Septal Puncture in Swine 
Even in experienced hands, X-ray guided needle atrial septal puncture risks non-target perforation and pericardial tamponade. Real-time MRI offers potentially superior target imaging and multiplanar device tracking. We report initial preclinical experience with real-time MRI-guided atrial septal puncture using a MRI-conspicuous blunt laser catheter that perforates only when energized.
Materials and Methods
We customized a clinical excimer laser catheter (0.9mm Clirpath, Spectranetics) with a receiver coil to impart MRI visibility at 1.5T. Seven swine underwent laser transseptal puncture under real-time MRI. MRI signal-to-noise profiles were obtained of the device in vitro. Tissue traversal force was tested with a calibrated meter. Position was corroborated by pressure, oximetry, angiography, and necropsy. Intentional non-target perforation simulated serious complication.
Embedded MRI-antennae accurately reflected the position of the laser catheter tip and profile in vitro and in vivo. Despite increased profile from the microcoil, the 0.9mm laser catheter traversed in vitro targets with similar force (0.22 ± 0.03N) compared with the unmodified laser.
Laser puncture of the atrial septum was successful and accurate in all animals. The laser was activated an average 3.8 ± 0.4 seconds before traversal. There were no sequelae after 6 hour observation. Necropsy revealed 0.9mm holes in the fossa ovalis in all animals.
Intentional perforation of the aorta and of the atrial free wall was evident immediately.
MRI-guided laser puncture of the interatrial septum is feasible in swine, and offers controlled delivery of perforation energy using an otherwise blunt catheter. Instantaneous soft-tissue imaging provides immediate safety feedback.
PMCID: PMC2587284  PMID: 18725098
Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard “closed-bore” 1.5T scanner.
Methods and Materials:
Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T2-weighted MRI.
Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V100) achieved was 94% (mean, 92%; 95% confidence interval, 89–95%). The urethral V125 ranged from 0% to 18% (median, 5%), and the rectal V75 ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients.
High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.
PMCID: PMC2396328  PMID: 15275727
Prostate cancer; Brachytherapy; MRI; Image guidance
9.  Real-Time Magnetic Resonance Imaging–Guided Stenting of Aortic Coarctation With Commercially Available Catheter Devices in Swine 
Circulation  2005;112(5):699-706.
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.
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.
PMCID: PMC1513629  PMID: 16043639
angioplasty; catheterization; coarctation; heart defects; congenital; stents
10.  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.
Materials and Methods
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 one 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.
PMCID: PMC1463249  PMID: 16532499
11.  Real-Time MRI-Guided Endovascular Recanalization of Chronic Total Arterial Occlusion in a Swine Model 
Circulation  2006;113(8):1101-1107.
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, magnetic resonance imaging (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 6–8 weeks, two underwent direct necropsy analysis for histology, three underwent primary X-ray-guided CTO recanalization attempts, and the remaining 14 underwent rtMRI-guided recanalization attempts in a 1.5T interventional MRI system. rtMRI 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 ± 1.6cm. rtMRI-guided CTO recanalization was successful in 11/14 swine and only 1/3 swine using X-ray alone. After unsuccessful rtMRI (n = 3), X-ray-guided attempts also were all unsuccessful.
Recanalization of long CTO is feasible entirely using rtMRI guidance. Low profile clinical-grade devices will be required to translate this experience to humans.
Endovascular recanalization of chronic total arterial occlusion (CTO) is challenging under conventional X-ray guidance because devices are advanced almost blindly. MRI can image CTO borders and luminal contents, and could potentially guide these procedures. We test the feasibility of real-time MRI guided wire traversal in a swine model of peripheral artery CTO using custom active MRI catheters.
PMCID: PMC1428785  PMID: 16490819
Real-time magnetic resonance imaging; Interventional MRI; Magnetic Resonance Imaging/methods
12.  Measurement of Skeletal Muscle Perfusion During Postischemic Reactive Hyperemia Using Contrast-Enhanced MRI With a Step-Input Function 
The regional distribution of skeletal muscle blood flow was measured during postischemic reactive hyperemia using Gd-DTPA contrast-enhanced (CE) MRI. The release of an occlusive thigh cuff was used to deliver a step-input of contrast concentration that was coincident with the onset of reactive hyperemia. A first-order tracer kinetic equation was used to estimate the unidirectional influx constant, Ki (ml/100 g/min), and the distribution volume of Gd-DTPA in the tissue, ve, from T1-weighted images acquired with saturation recovery (SR) steady-state free precession (SSFP) and spoiled gradient-echo (SPGR) protocols. The capillary permeability surface (PS) area increased significantly during reactive hyperemia, which facilitated rapid extraction of Gd-DTPA during the first pass. Regional muscle group studies from 11 normal volunteers yielded blood flow (Ki) values of 108.3 ± 34.1 ml/100 g/min in the gastrocnemius, 184.3 ± 41.3 ml/100 g/min in the soleus, and 122.4 ± 34.4 ml/100 g/min in the tibialis anterior. The distribution volumes (ve) in the corresponding muscle groups were respectively 8.3% ± 2.1%, 9.3% ± 1.9%, and 7.9% ± 1.8% from the kinetic model, and 8.8% ± 2.4%, 9.1% ± 1.9%, and 7.2% ± 1.4% from tissue relaxometry studies. Bulk blood flow studies in the same volunteers using phase-contrast velocimetry (popliteal artery) yielded significantly lower flow values, but with a correlation coefficient R2 = 0.62 and P = 0.004.
PMCID: PMC1356658  PMID: 16032661
blood flow; peripheral artery disease; claudication; angiogenesis; MRI
13.  Invasive Human Magnetic Resonance Imaging: Feasibility During Revascularization in a Combined XMR Suite 
We tested the feasibility and safety of invasive magnetic resonance imaging (MRI) during peripheral angioplasty. Real-time MRI can image soft tissue and may potentially guide therapeutic procedures without ionizing radiation or nephrotoxic contrast. MRI-guided diagnostic catheterization has been described recently, but safe and conspicuous catheter devices are not widely available. An active guidewire, which serves as an MRI receiver antenna, might be useful to guide catheterization or even to image atheroma. We describe a combined interventional suite offering both X-ray fluoroscopy and real-time MRI. We used a 0.030″ active guidewire receiver coil for invasive MRI after X-ray lesion traversal in patients undergoing percutaneous iliofemoral artery revascularization. Intra-vascular MRI was compared with noninvasive MRI, X-ray angiography, and intravascular ultrasound (IVUS). Seven eligible patients consented to participate, but three were excluded because of lengthy revascularization procedures. Four remaining patients safely underwent combined X-ray fluoroscopy and real-time magnetic resonance imaging (XMR) transport, continuous monitoring, and all imaging modalities. There was no device dislodgment, contamination or evidence of heating. The intravascular MRI coil was well visualized except at the tip, but did not provide superior mural imaging compared with IVUS. Therefore, because an adequate safety and workflow experience was obtained, enrollment was terminated after only four subjects. Invasive MRI is feasible and apparently safe during peripheral angioplasty. Patients can safely be transported and monitored in an XMR interventional suite. An active quarter-wavelength guidewire coil does not provide superior imaging compared with IVUS, but provides satisfactory guide-wire visualization. These tools may prove useful for advanced therapeutic procedures in the future.
PMCID: PMC1317610  PMID: 15736247
interventional magnetic resonance imaging; angioplasty; invasive imaging; catheterization; peripheral artery disease

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