Interventional cardiovascular magnetic resonance: still tantalizing

Surgical procedures afford direct exposure for visualization (optical imaging) of target tissue and access for mechanical intervention. This permits instant recognition of important complications like bleeding to allow immediate correction during the procedure. Unfortunately surgical exposure is morbid, meaning it produces physiological and geometric derangement, discomfort, immobilization, and risk.

While the actual risk of radiation injury remains controversial, even low-level exposure to ionizing radiation is thought to contribute to the long-term risk of malignancy [1, 2]. Children are considered more sensitive to radiation and may live longer to experience radiation toxicity. Children requiring catheterization for congenital heart disease often require multiple procedures over time. Chromosomal damage was evident in the peripheral blood of children exposed to catheterization-related radiation [3].

Diagnostic MR utilizes longer image acquisition (for example ECG-gated segmented MR) and off-line reconstruction for higher image quality. Real-time MR combines acquisition, reconstruction, and display to provide operators images with low latency, empirically less than 250 ms compared with 100 ms for X-ray fluoroscopy. X-ray fluoroscopy produces 15 relatively sparse frames per second with a pixel matrix of 1024 × 1024 and a field of view of 8–40 cm. In real-time MR, the imaging matrix (and thus spatial resolution) is reduced in size to support an imaging speed between 5 and 10 frames per second [4]. Even at a reduced pixel imaging matrix such as 192 × 128 at 8 acquired frames per second, real-time MR is comparably information-rich. Most modern real-time MR implementations employ balanced steady state free precession (SSFP, also known as TrueFISP, bFFE, or FIESTA) techniques because of efficient use of magnetization, high SNR, and short repetition times. Fast spin echo techniques produce excellent image quality, but are less attractive for real-time applications because of higher specific absorption rates (SAR) of heat from radiofrequency energy and longer acquisition times. In addition to conventional rectilinear sampling strategies, spiral and radial trajectories are also well-suited for real-time imaging [5, 6].

Image acquisition speeds may be accelerated through partial and/or parallel acquisition schemes. Partial acquisitions asymmetrically skip some data acquisition in either the frequency (partial echo) or phase encoding direction, and the missing data is synthesized with techniques such as homodyne reconstruction [7] or projection onto convex sets [8]. Parallel acquisition schemes acquire undersampled datasets by skipping some phase-encoding lines, and exploit the sensitivity profiles of multiple coils to reconstruct the missing data. The two most commonly used algorithms for parallel image reconstruction are SENSE [9, 10] and GRAPPA [11]; with specialized coil arrays and sufficient computational horsepower, four-fold acceleration rates are typically achieved [12] (vide infra). The computational demands on image reconstruction are greatly increased, but real-time interactive imaging with TSENSE has been demonstrated using computers with multiple CPUs [13].

The major commercial MR systems provide real-time SSFP capability with interactive graphic slice prescription during continuous scanning. Some interventional implementations use separate external reconstruction computer systems operating in parallel, having bidirectional links for scan control, providing rapid image reconstruction. Guttman, McVeigh, and Ozturk developed such a comprehensive interactive real-time MR reconstruction system for interventional applications at NIH [14]. This system features real-time imaging of multiple slices and displays these slices in their relative three-dimensional position. Perhaps most important is the ability independently to process and highlight signals from individual receiver channels, especially those attached to intravascular devices [15]. Highlighted devices are then easily distinguished from each other and surrounding tissue, providing high user confidence in iCMR guidance. Other interactive features we have found useful include device-only projection imaging, electrocardiographic gating to suspend cardiac motion and saturation pre-pulses to enhance the appearance of gadolinium during injections into arteries, devices, or myocardium having late gadolinium enhancement. Image-acceleration is controlled interactively. It has proven useful to apply subtraction masks for interactive real-time digital-subtraction MR angiography [16].

Santos and colleagues at Stanford University have developed a real-time MR system (RTHawk), which allows dynamic switching between pulse sequences and reconstruction algorithms [17]. This system enables the user to rapidly switch between low spatial resolution localizers and high spatial resolution images, analogous to "fluoroscopy" and "cineangiography" X-ray modes. The system also accommodates active device tracking by interspersing 3 orthogonal projections for device localization and real-time overlay of the device position on anatomical images.

Device-scanner interaction also can be automated. For example, the group at Case Western Reserve University automatically increases temporal resolution and field of view when rapid device motion is detected, then increases spatial resolution and decreases field of view when device motion is low [18]. The effect is to "zoom in" and slow down for more accurate imaging during fine device positioning [18].

Our investigational interventional procedures are guided by multiple slices acquired and displayed in rapid succession. A three-dimensional volume-rendering of the slices conveys their relative positions. Updates of individual slices can be paused or reactivated as needed during a procedure. This type of display can further be enhanced by permitting the user interactively to apply point markers on important anatomic features or targets, make measurements on-line, and combine with prior roadmap images to make rapid before-after comparisons.

Many of these concepts have been incorporated into an "Interactive Front End" system developed by Christine Lorenz of Siemens Medical Systems and available for investigational use [19].

iCMR operators have two general imaging approaches. For some applications, imaging is directed at target pathology, while devices are manipulated in or out of the desired target slice. Alternatively, the real-time imaging slice can automatically track catheter movements and alter the slice prescription so as always to keep the desired catheter device in view, while changing the view of the neighboring anatomy. Ideally, both imaging techniques should be available to the operator. We have found a "projection-mode" feature useful during catheter manipulations within target slices. When parts of catheter devices move outside of a typical thin-slice image, they are no longer visible to the operator. By toggling projection-mode (which switches to thick-slice or non slice-selective imaging), the catheter can be "found" and manipulated back into the target slice. Combining an "adaptive" projection mode (automatically orthogonal to the selected viewing angle) with multi-slice three-dimensional rendering has been especially useful (Figure 1).

This section attempts to answer questions raised during site visits. Readers are cautioned our recent first-hand experience is limited to one system vendor.

iCMR would probably already be in widespread use if conspicuous and safe clinical-grade catheters were readily available. The gap reflects the complexity of such devices and limited perceived return on industry investment.

Interventional MR catheter devices (Figure 3) are typically classified as "passive" or "active" depending on whether they are visualized based on intrinsic materials properties (passive) or based on signals from embedded receiver coils and electronics (active). Hybrids and combinations are also attractive options. The different approaches are summarized in Table 1.

As mentioned above, because most iCMR procedures use two-dimensional thin slices, parts of a flexible catheter may move outside the selected imaging slice. This is especially important with regards to the tip of a catheter. In this way iCMR and two-dimensional ultrasound-guided procedures differ substantially from projection X-ray fluoroscopy-guided procedures. In iCMR we compensate using interactive projection modes.

Because MR affords flexible contrast and views at the expense of reduced temporal resolution or signal-noise, certain procedures are well suited for ICMR. These include tissues that are large or thick-walled relative to attainable fields of view (such as heart and aorta), tissue targets imaged with high contrast compared with surrounding tissue (such as myocardium against blood), and targets that are relatively immobile (such as peripheral arteries). Structures that can be contained within a single imaging plane (such as straight segments of iliac arteries) can be imaged rapidly, compared with small tortuous structures such as coronary arteries, which are difficult to image in real-time. Ventricular myocardium is especially attractive in spite of cardiac and respiratory motion because it is large, thick-walled, and well depicted with high contrast using SSFP compared with cavitary blood. Conversely, thin-walled cardiac atria are difficult to image even using segmented MR.

Speuntrup et al[81] delivered passively-visualized stainless steel stents in coronary arteries of normal swine. The devices and target proximal coronary arteries were imaged superbly using SSFP at 1.5 T despite cardiac motion and small targets. Unfortunately, barring significant technical breakthroughs, meaningful human coronary interventional procedures are unlikely to be performed under iCMR guidance. X-ray fluoroscopy offers high temporal (33–66 ms) and spatial (200–500 μm) resolution, allowing operators to navigate sophisticated 0.35 mm (0.014") diameter guidewires through small, heterogeneous, tortuous, calicified, and even occluded coronary arteries.

Simple peripheral angioplasty is conducted effectively under X-ray guidance, so iCMR guidance is not compelling as a standalone application. Widely available, iCMR might be an attractive radiation-free alternative that also adds the ability to image uncommon complications such as peri-vascular hemorrhage.

MR has been used to conduct transluminal angioplasty [31, 82‐85] and stenting [51, 69, 86‐92] in animal models of iliac, renal, and carotid arteries.

The team at the University of Regensberg has performed MR guided angioplasty and stenting in humans, using only passive devices, of iliac [93] and of femoropopliteal [94] atherosclerotic lesions.

The aorta is the largest artery, and proximal aortic interventions are complex under any circumstances. X-ray alone is imperfect in visualizing complex three-dimensional aneurysms. Endovascular repair for aortic aneurysm is limited in part by endoleak due to inflow or outflow malapposition. Raman and colleagues [95] used MR to guide simple endograft tube repair of abdominal aortic aneurysm in pig models. Homemade temporarily-active endograft devices, which were depicted with color-highlighting until they were disconnected as RF coils after deployment, were more straightforward to use and more successful than comparable passive endograft devices. Endograft treatment under MR restored a normal lumen contour and laminar flow. Moreover, MR demonstrated device apposition to the target aortic wall and allowed interrogation for endoleak.

Eggebrecht and colleagues in Essen, Germany, elegantly applied iCMR to guide the placement of stent grafts in an animal model of thoracic aortic dissection [96]. They used off-the-shelf passive clinical self-expanding Gore TAG endografts without a guidewire. MR clearly revealed the true and false lumens of the dissected aorta, guided stent-graft deployment, and demonstrated stent-graft obliteration of the dissection and false lumen. This was an excellent demonstration of the value of simultaneous tissue and device imaging to guide a complex procedure (Figure 6).

Our team used active guidewires to treat an animal model of aortic coarctation with platinum-iridium stents [51]. Passive balloons filled with dilute gadolinium appeared bright over this active guidewire, and MR was helpful in displaying both target tissue and stent system during deployment. Velocity-encoded MR confirmed the hemodynamic results of the procedure. More important, MR provided immediate evidence of life-threatening rupture after intentional overstretch of the coarctation. In patients this recognition would provide precious additional time for rescue. Of note, the same procedure was far less effective when conducted using passive instead of active guidewires (Figure 4). Other teams [97‐99] have modeled passive aortic endograft deployment in vitro or in vivo.

Krueger, Kuehne, and colleagues in Berlin performed balloon angioplasty of aortic coarctation lesions in patients during MR. This was an important first clinical step toward wholly MR-guided treatment of this congenital lesion [22] (Figure 7).

Perhaps more compelling are applications that exploit the ability of MR to visualize vascular spaces not conspicuous using X-ray. X-Ray with radiocontrast identifies the arteries up- and down-stream of the occlusion, but the occluded segment itself has no lumen to fill with radiocontrast and therefore remains invisible to the operator. "Blind" device manipulation risks procedural failure and arterial perforation. MR can visualize both patent and occluded artery segments, as well as the wall, lumen content, and adjacent structures, so it is attractive to guide recanalization [100].

Raval and colleagues created an animal model of peripheral artery chronic total occlusion in swine. They recanalized these lesions using homemade active devices under MR, even though they were fairly unsuccessful using X-ray and high-performance clinical guidewires [101]. MR helped operators traverse complex occlusions while keeping equipment inside the walls of the target artery. This is especially important in recanalization of tortuous peripheral artery occlusions, such as the iliac arteries.

Clinical-grade devices are currently under development to translate this experience into humans [102]. The group in Sunnybrook Hospital has developed a novel forward-looking catheter coil to guide recanalization using orthogonal solenoids.

Non-surgical replacement of heart valves has become feasible, despite challenges in miniaturization, access, and image-guided positioning. MR might aid in positioning relative to vital structures such as coronary artery ostia. Kuehne and colleagues [103] have reported preliminary experience deploying a passively-visualized nitinol-based aortic valve prosthesis from a transfemoral approach in healthy swine. Their work demonstrates the value of combined device and tissue imaging for precise placement of critical prostheses. Such work may have value in complex pulmonary valve implants in patients with prior surgery for congenital heart disease.

Horvath, Guttman, and McVeigh at NIH have pursued operative MR guidance for cardiac surgery [104]. Using a minimally invasive incision to access the apex of the beating left ventricle, they have implanted commercial bioprosthetic heart valves mounted on stent devices into the aortic valve position. MR aided in axial and rotational positioning of the valve prosthesis with relation to the aortic annulus and coronary artery ostia. The same team is enhancing an MR-compatible robot for surgical applications [105]. MR-trackable thoracoscopes have been described to combine MR-derived anatomic "context" with optical imaging and direct instrument access [106].

Diagnostic catheterization in patients with congenital heart disease is more complex and challenging than in adults with acquired heart disease, and may not be guided by ordinary anatomic predictions. Hearts after multiple palliative interventions have additional morphological complexity.

Schalla and colleagues at University of California San Francisco simulated clinical-grade pediatric diagnostic catheterization in an animal model of atrial septal defect, using active-tracking catheter devices. They combined invasive hemodynamic measurements with velocity-encoded MR [107]. Others have reported less complex procedures in animals [108, 109].

The pioneering clinical diagnostic MR catheterization at Kings College London remains the landmark in the field [110]. Since this first report, they have conducted hundreds of diagnostic catheterization procedures in children using passive devices and CO₂-filled balloons in a combined X-ray and MR suite (Figure 3d). In addition, they routinely conduct interventional procedures overlaying MR-derived roadmaps with live X-ray (see X-ray Fused with MR or XFM, below). Patients undergoing MR-assisted catheterization suffered significantly less radiation exposure than those undergoing conventional X-ray procedures.

The Kings College team [111, 112] as well as Kuehne and colleagues [113] at Berlin Charité Hospital have used MR catheterization to make critical vessel-specific determinations of pulmonary vascular flow and resistance in patients with congenital heart disease or pulmonary artery disease. These may overcome inherent limitations of oximetry-derived measurements.

At least three teams have described iCMR guided deployment of nitinol occluder devices in animal atrial septal defects [114‐116]. This application may not be superior to conventional or newer ultrasound guidance. Ventricular septal defect suffers additional morphological and procedural complexity that may benefit from iCMR.

An especially attractive application of iCMR is the intentional violation of ordinary tissue spaces. A simple step in this direction is to connect adjacent vascular structures during atrial septal puncture. Arepally and colleagues at Johns Hopkins University [117] first described MR guided puncture of the interatrial septum using an active Brockenbrough-style needle. Our lab [45] conducted similar transseptal puncture and balloon septostomy, with MR assessment of the intracardiac shunts created. MR has particular value in specific identification and location of the "dangerous" tip compared with two-dimensional ultrasound. We did similar atrial septal puncture using an ablative laser catheter with an active-imaging distal tip coil [118], which by virtue of its flexibility could be applied in the future to more challenging geometry and more elaborate procedures.

Arepally and colleagues also used a similar active needle to effect a transcatheter mesocaval shunt, connecting the vena cava and the superior mesenteric vein using a nitinol connector [117]. They have also used this approach to deliver iron-labeled pancreatic beta-cell microcapsules under MR guidance to treat a model of islet-cell deficiency diabetes mellitus [119].

Using a unique double-doughnut MR configuration containing an integrated flat-panel X-Ray fluoroscopy system, Kee and colleagues at Stanford conducted preclinical [120] and clinical [121] transjugular intrahepatic portosystemic shunt (TIPS) procedures, which connect the hepatic and portal venous circulations in portal hypertension syndromes. MR guidance reduced the number of unsuccessful punctures, which can be hazardous.

Used this way, iCMR might enable non-surgical connections between other non-adjacent vascular structures, for example connecting the subclavian and pulmonary arteries, or the aorta and femoral arteries. Catheter-based extra-anatomic bypass might be an attractive alternative to open-surgical bypass, and is under active development. MR should permit inspection of vascular and extravascular spaces, the trajectory of connecting devices, and instantaneous assessment of the adequacy of catheter-based anastomoses.

Several labs [25, 122‐129] have used iCMR and active or passive catheters to deliver cells and other materials into specified targets in normal and infarcted animal hearts. As described above, thick myocardial walls and high contrast with blood during SSFP MR afford excellent image guidance, and targeting based on multiple factors including late gadolinium enhancement, wall motion abnormalities, thickness, or anatomic position. Labeling or admixing injectate with contrast agents helps to confirm successful delivery, to assess intramyocardial redistribution, to assure confluent treatment volumes, or to avoid inadvertent injection overlap. The long-term value of exogenous intracellular contrast for tracking cell fate is at best controversial [130, 131]. Promising therapeutic cell preparations have not yet been identified at the time of this writing. Should precise targeting be valuable for a future cell preparation, iCMR could be a valuable delivery tool.

In this family of procedures, cardiac rhythm pathways are mapped and interrupted by focused energy delivery or surgery. In catheter approaches, plans or even maps are routinely constructed using intracardiac electrograms and/or adjunctive X-ray, ultrasound, or imported tomographs. Multipolar pacing and ablation catheters are then guided by combinations of these images and maps and even can be directed by external magnetic deflection. Ablation lesions are interactively assessed by local heating and the impact on local and regional electrograms and rhythms, but not generally by imaging. In a surgical approach, anatomic myocardial segments are insulated from others under direct visualization. iCMR might afford surgical-style anatomic imaging guidance to catheter procedures, in positioning and in depicting actual ablation lesions during procedures [132].

MR with or without late gadolinium enhancement might have clinical value in identifying early tissue response to radiofrequency ablations [133‐135], ablation lesions and perhaps lines of continuity as an imaging correlate of functional electrophysiologic block in thin walled atrial tissue [132, 136, 137], and the complex substrate of ventricular tachycardia [138]. MR already is in widespread clinical use overlaid with live X-ray or electroanatomical maps [139‐142].

Henry Halperin's team at Johns Hopkins University first described active-imaging MR catheters with appropriate filtering to acquire intracardiac electrograms during real-time MR [143]. In a recent landmark study, they obtained first-in-man intracardiac electrograms in patients during MR [144] (Figure 8).

Vivek Reddy and colleagues at Massachusetts General Hospital in collaboration with General Electric [36] developed and tested novel real-time MR tracking of electrophysiology catheters in animals overlaid on high-resolution time-resolved MR images of myocardium obtained in the same system (Figure 9).

iCMR has been used to deploy prophylactic inferior vena cava filters in order to arrest ascending thromboembolism [145‐148] and to visualize captured embolic material.

MR also has been used to guide visceral artery embolization, such as kidney segments, and affected parenchyma [149, 150]. The Northwestern University team has coated polyvinyl alcohol particles with gadolinium chelates to monitor transcatheter arterial embolization procedures [151].

MR may have incremental value in tissue monitoring and assessment during and after interventional procedures, affecting for example renal [152] and myocardial parenchyma [153].

Clinically, Omary and colleagues at Northwestern University have been active in conducting clinical embolotherapy procedures in a combined X-ray and MR suite. MR perfusion assessment helped guide uterine artery embolization for leiomyoma (fibroids) [154]. Similarly they have used MR to monitor hepatic chemoembolization procedures for malignancy [155].

Bozlar and colleagues at University of Virginia [156] reported an innovative application of selective intraarterial contrast enhanced MR angiography. They subtracted intraarterial gadolinium MR contrast images from systemic (intravenous) contrast images to identify feeding collateral arteries in a pelvic arteriovenous malformation. Solely diagnostic applications of selective intraarterial contrast enhanced MR angiography [157] are less compelling than those combined with therapeutic procedures [16].

Fahrig and colleagues at Stanford University developed a hybrid X-ray and MR system based on a double-donut MR scanner, with an X-ray source and detector mounted inside the magnet bore [158, 159]. Images can be acquired alternately from X-ray and MR without moving the patient, providing images that are automatically co-registered. Several innovations have come out of the development of this system, such as X-ray transparent aluminum MR coils [160]. This system has been used clinically for transjugular intrahepatic portosystemic shunt (TIPS) creation [121] as described above. In addition, a system based on a 1.5 T closed bore system, with the X-ray gantry mounted just outside the magnet has been proposed [161].

MR roadmaps can be combined with live X-ray fluoroscopy using a conventional clinical environment and conventional catheter equipment, to provide additional anatomic landmarks and functional information to guide procedures [162, 163].

In addition to the registration of the MR and X-ray coordinate systems, the X-ray system must be calibrated to compensate for image distortions. These orientation-dependent distortions are caused by C-arm imperfections (e.g. pincushion distortions, gantry fatigue) and the influence of the MR system's main magnetic field on the X-ray image intensifier. Using two-dimensional and three-dimensional phantoms with fiducial markers at known locations, warping polynomials may be calculated which can be used for distortion correction [164, 165]. These distortions are less important using contemporary flat-panel X-ray detectors.

In order to merge MR and X-ray images, the coordinate systems of each must be aligned. The approach taken by Razavi is to use a calibration phantom, which can accommodate X-ray or MR compatible markers, to compute the transformation between MR scanner space and X-ray table space. The position of the X-ray components are tracked using infrared emitting diodes placed on the X-ray C-arm and table. An additional marker may be placed on the patient's chest to allow for adjustments to the registration to be made in case of gross patient motion [140, 162].

In our lab, registration is accomplished by placing multi-modality external fiducial markers either directly on the patient's skin or in an elastic band around the patient's torso. The markers contain a mixture of iodinated X-ray contrast and gadolinium based MR contrast, so that they can easily be identified in both imaging modalities. A three-dimensional MR T1-weighted acquisition and a set of multiple baseline X-ray projections are used to register the two coordinate systems. Using custom built software, the three-dimensional positions of the markers are automatically reconstructed from the MR and X-ray images, correspondence between the markers is established, and a three-dimensional rigid registration algorithm is used to align the MR coordinate system with the X-ray coordinate system.

Relevant anatomic landmarks (e.g. myocardial surfaces, the great vessels, cardiac valves) and treatment sites (e.g. ventricular septal defect, myocardial infarct, injection target) are segmented on MR images and can be color-coded. Two-dimensional projections of these three-dimensional contours are constructed based on the X-ray gantry orientation, registration calculations, and calibration data. These projections are overlaid on the X-ray fluoroscopy images and displayed in the angiography suite (Figure 10). Position information from the X-ray system (c-arm angle, table position, magnification factor) is used automatically to adjust the displayed MR derived contours with the fluoroscopic images during a procedure.

The Kings College London team uses X-ray Fused with MR (XFM) to provide soft tissue context to clinical electrophysiology procedures [162] and pediatric interventional procedures. Our lab has used XFM to guide cell delivery to infarct targets with millimeter precision, using targets such as infarct borders or zones of excessive thinning [166]. We also have used XFM to guide a novel antegrade approach to catheter-based repair of membranous ventricular defect in swine (Figure 10), which significantly shortened X-ray exposure compared with the conventional retrograde approach [167], as well as a novel approach to catheter-based mitral annuloplasty involving an intramyocardial guidewire trajectory. In patients we have used XFM to facilitate biopsy of high risk cardiac structures, and to aid in recanalization of chronic total peripheral artery occlusion [163].

A significant limitation of the XFM type roadmap approaches is that out-of-date roadmap information can be misleading or hazardous. Roadmap information can be distorted by rigid devices, by changes in the underlying tissue structure related to the intervention, and from uncorrected cardiac and respiratory motion.