Anthony Z. Faranesh

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. Magn Reson Med 54:289–298, 2005. Published 2005 Wiley‐Liss, Inc.

Real-time MRI-guided right heart catheterization in adults using passive catheters

AIMS 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. CONCLUSION 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.

Antegrade Percutaneous Closure of Membranous Ventricular Septal Defect Using X-Ray Fused With Magnetic Resonance Imaging

OBJECTIVES We hypothesized that X-ray fused with magnetic resonance imaging (XFM) roadmaps might permit direct antegrade crossing and delivery of a ventricular septal defect (VSD) closure device and thereby reduce procedure time and radiation exposure. BACKGROUND Percutaneous device closure of membranous VSD is cumbersome and time-consuming. The procedure requires crossing the defect retrograde, snaring and exteriorizing a guidewire to form an arteriovenous loop, then delivering antegrade a sheath and closure device. METHODS Magnetic resonance imaging roadmaps of cardiac structures were obtained from miniature swine with spontaneous VSD and registered with live X-ray using external fiducial markers. We compared antegrade XFM-guided VSD crossing with conventional retrograde X-ray-guided crossing for repair. RESULTS Antegrade XFM crossing was successful in all animals. Compared with retrograde X-ray, antegrade XFM was associated with shorter time to crossing (167 +/- 103 s vs. 284 +/- 61 s; p = 0.025), shorter time to sheath delivery (71 +/- 32 s vs. 366 +/- 145 s; p = 0.001), shorter fluoroscopy time (158 +/- 95 s vs. 390 +/- 137 s; p = 0.003), and reduced radiation dose-area product (2,394 +/- 1,522 mG.m(2) vs. 4,865 +/- 1,759 mG.m(2); p = 0.016). CONCLUSIONS XFM facilitates antegrade access to membranous VSD from the right ventricle in swine. The simplified procedure is faster and reduces radiation exposure compared with the conventional retrograde approach.

Transatrial Intrapericardial Tricuspid Annuloplasty

OBJECTIVES This study sought to demonstrate transcatheter deployment of a circumferential device within the pericardial space to modify tricuspid annular dimensions interactively and to reduce functional tricuspid regurgitation (TR) in swine. BACKGROUND Functional TR is common and is associated with increased morbidity and mortality. There are no reported transcatheter tricuspid valve repairs. We describe a transcatheter extracardiac tricuspid annuloplasty device positioned in the pericardial space and delivered by puncture through the right atrial appendage. We demonstrate acute and chronic feasibility in swine. METHODS Transatrial intrapericardial tricuspid annuloplasty (TRAIPTA) was performed in 16 Yorkshire swine, including 4 with functional TR. Invasive hemodynamics and cardiac magnetic resonance imaging (MRI) were performed at baseline, immediately after annuloplasty and at follow-up. RESULTS Pericardial access via a right atrial appendage puncture was uncomplicated. In 9 naïve animals, tricuspid septal-lateral and anteroposterior dimensions, the annular area and perimeter, were reduced by 49%, 31%, 59%, and 24% (p < 0.001), respectively. Tricuspid leaflet coaptation length was increased by 53% (p < 0.001). Tricuspid geometric changes were maintained after 9.7 days (range, 7 to 14 days). Small effusions (mean, 46 ml) were observed immediately post-procedure but resolved completely at follow-up. In 4 animals with functional TR, severity of regurgitation by intracardiac echocardiography was reduced. CONCLUSIONS Transatrial intrapericardial tricuspid annuloplasty is a transcatheter extracardiac tricuspid valve repair performed by exiting the heart from within via a transatrial puncture. The geometry of the tricuspid annulus can interactively be modified to reduce severity of functional TR in an animal model.

Patient-Adaptive Reconstruction and Acquisition in Dynamic Imaging with Sensitivity Encoding (PARADISE)

MRI of the human heart without explicit cardiac synchronization promises to extend the applicability of cardiac MR to a larger patient population and potentially expand its diagnostic capabilities. However, conventional nongated imaging techniques typically suffer from low image quality or inadequate spatio‐temporal resolution and fidelity. Patient‐Adaptive Reconstruction and Acquisition in Dynamic Imaging with Sensitivity Encoding (PARADISE) is a highly accelerated nongated dynamic imaging method that enables artifact‐free imaging with high spatio‐temporal resolutions by utilizing novel computational techniques to optimize the imaging process. In addition to using parallel imaging, the method gains acceleration from a physiologically driven spatio‐temporal support model; hence, it is doubly accelerated. The support model is patient adaptive, i.e., its geometry depends on dynamics of the imaged slice, e.g., subjects heart rate and heart location within the slice. The proposed method is also doubly adaptive as it adapts both the acquisition and reconstruction schemes. Based on the theory of time‐sequential sampling, the proposed framework explicitly accounts for speed limitations of gradient encoding and provides performance guarantees on achievable image quality. The presented in‐vivo results demonstrate the effectiveness and feasibility of the PARADISE method for high‐resolution nongated cardiac MRI during short breath‐hold. Magn Reson Med, 2010.

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Adaptive noise cancellation to suppress electrocardiography artifacts during real-time interventional MRI.

To develop a system for artifact suppression in electrocardiogram (ECG) recordings obtained during interventional real‐time magnetic resonance imaging (MRI).

MRI active guidewire with an embedded temperature probe and providing a distinct tip signal to enhance clinical safety

BackgroundThe field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.035” (0.89 mm) guidewire for MRI right and left heart catheterization at 1.5 T that has an internal probe to monitor temperature in real-time, and that has both tip and shaft visibility as well as suitable flexibility.MethodsThe design has an internal fiberoptic temperature probe, as well as a distal solenoid to enhance tip visibility on a loopless antenna. We tested different tip-solenoid configurations to balance heating and signal profiles. We tested mechanical performance in vitro and in vivo in comparison with a popular clinical nitinol guidewire.ResultsThe solenoid displaced the point of maximal heating (“hot spot”) from the tip to a more proximal location where it can be measured without impairing guidewire flexion. Probe pullback allowed creation of lengthwise guidewire temperature maps that allowed rapid evaluation of design prototypes. Distal-only solenoid attachment offered the best compromise between tip visibility and heating among design candidates. When fixed at the hot spot, the internal probe consistently reflected the maximum temperature compared external probes.Real-time temperature monitoring was performed during porcine left heart catheterization. Heating was negligible using normal operating parameters (flip angle, 45°; SAR, 1.01 W/kg); the temperature increased by 4.2°C only during high RF power mode (flip angle, 90°; SAR, 3.96 W/kg) and only when the guidewire was isolated from blood cooling effects by an introducer sheath. The tip flexibility and in vivo performance of the final guidewire design were similar to a popular commercial guidewire.ConclusionsWe integrated a fiberoptic temperature probe inside a 0.035” MRI guidewire. Real-time monitoring helps detect deleterious heating during use, without impairing mechanical guidewire operation, and without impairing MRI visibility. We therefore need not rely on prediction to ensure safe clinical operation. Future implementations may modulate specific absorption rate (SAR) based on temperature feedback.

Robust automatic rigid registration of MRI and X-ray using external fiducial markers for XFM-guided interventional procedures

PURPOSE In X-ray fused with MRI, previously gathered roadmap MRI volume images are overlaid on live X-ray fluoroscopy images to help guide the clinician during an interventional procedure. The incorporation of MRI data allows for the visualization of soft tissue that is poorly visualized under X-ray. The widespread clinical use of this technique will require fully automating as many components as possible. While previous use of this method has required time-consuming manual intervention to register the two modalities, in this article, the authors present a fully automatic rigid-body registration method. METHODS External fiducial markers that are visible under these two complimentary imaging modalities were used to register the X-ray images with the roadmap MR images. The method has three components: (a) The identification of the 3D locations of the markers from a full 3D MR volume, (b) the identification of the 3D locations of the markers from a small number of 2D X-ray fluoroscopy images, and (c) finding the rigid-body transformation that registers the two point sets in the two modalities. For part (a), the localization of the markers from MR data, the MR volume image was thresholded, connected voxels were segmented and labeled, and the centroids of the connected components were computed. For part (b), the X-ray projection images, produced by an image intensifier, were first corrected for distortions. Binary mask images of the markers were created from the distortion-corrected X-ray projection images by applying edge detection, pattern recognition, and image morphological operations. The markers were localized in the X-ray frame using an iterative backprojection-based method which segments voxels in the volume of interest, discards false positives based on the previously computed edge-detected projections, and calculates the locations of the true markers as the centroids of the clusters of voxels that remain. For part (c), a variant of the iterative closest point method was used to find correspondences between and register the two sets of points computed from MR and X-ray data. This knowledge of the correspondence between the two point sets was used to refine, first, the X-ray marker localization and then the total rigid-body registration between modalities. The rigid-body registration was used to overlay the roadmap MR image onto the X-ray fluoroscopy projections. RESULTS In 35 separate experiments, the markers were correctly registered to each other in 100% of the cases. When half the number of X-ray projections was used (10 X-ray projections instead of 20), the markers were correctly registered in all 35 experiments. The method was also successful in all 35 experiments when the number of markers was (retrospectively) halved (from 16 to 8). The target registration error was computed in a phantom experiment to be less than 2.4 mm. In two in vivo experiments, targets (interventional devices with pointlike metallic structures) inside the heart were successfully registered between the two modalities. CONCLUSIONS The method presented can be used to automatically register a roadmap MR image to X-ray fluoroscopy using fiducial markers and as few as ten X-ray projections.

Integration of cardiac and respiratory motion into MRI roadmaps fused with x-ray

PURPOSE Volumetric roadmaps overlaid on live x-ray fluoroscopy may be used to enhance image guidance during interventional procedures. These roadmaps are often static and do not reflect cardiac or respiratory motion. In this work, the authors present a method for integrating cardiac and respiratory motion into magnetic resonance imaging (MRI)-derived roadmaps to fuse with live x-ray fluoroscopy images, and this method was tested in large animals. METHODS Real-time MR images were used to capture cardiac and respiratory motion. Nonrigid registration was used to calculate motion fields to deform a reference end-expiration, end-diastolic image to different cardiac and respiratory phases. These motion fields were fit to separate affine motion models for the aorta and proximal right coronary artery. Under x-ray fluoroscopy, an image-based navigator and ECG signal were used as inputs to deform the roadmap for live overlay. The in vivo accuracy of motion correction was measured in four swine as the ventilator tidal volume was varied. RESULTS Motion correction reduced the root-mean-square error between the roadmaps and manually drawn centerlines, even under high tidal volume conditions. For the aorta, the error was reduced from 2.4 ± 1.5 mm to 2.2 ± 1.5 mm (p < 0.05). For the proximal right coronary artery, the error was reduced from 8.8 ± 16.2 mm to 4.3 ± 5.2 mm (p < 0.001). Using real-time MRI and an affine motion model it is feasible to incorporate physiological cardiac and respiratory motion into MRI-derived roadmaps to provide enhanced image guidance for interventional procedures. CONCLUSIONS A method has been presented for creating dynamic 3D roadmaps that incorporate cardiac and respiratory motion. These roadmaps can be overlaid on live X-ray fluoroscopy to enhance image guidance for cardiac interventions.