MR guidance prepares to enter endovascular realm

Interventional MRI is an established clinical tool for the biopsy of lesions that are difficult or impossible to delineate or that cannot be reached easily by any other modality. Liver and breast lesions often fall into the first category. Subdiaphragmatic liver lesions benefit particularly from the free choice of imaging planes offered by MRI.

MR-guided endovascular interventions are seldom performed in humans, despite encouraging results from animal studies. Potential advantages include high soft tissue contrast, the ability to perform unenhanced and contrast-enhanced angiography, the ability to acquire physiological data such as flow and ventricular function, and promises of “molecular imaging.”

The biggest obstacle to broader clinical acceptance of MR-guided endovascular intervention is the lack of MR-compatible instruments. Researchers have commonly made their own devices for animal studies, or used dedicated prototypes that are not commercially available for clinical studies.

Only a few devices used routinely in conventional angiography are MR-compatible. Most catheters are braided metal to improve torque and steerability. Such braiding can turn catheters into radiofrequency (RF) antennae, increasing the risk of their heating up and introducing artifacts on images. Nitinol guidewires face the same problem (Figure 1).

Endovascular MR-guided interventions have been promoted as a way of sparing patients and practitioners from ionizing radiation. Procedures that would typically be followed on fluoroscopy were carried out under realtime MRI guidance in animals, allowing interventional radiologists to gain practical experience. The dosereduction argument was not sufficiently compelling, though, and the majority of endovascular x-ray–guided interventions have not been moved to the MRI suite. One notable exception is the diagnosis and treatment of patients with congenital heart disease. In general, however, the method has not made the critical step from the research laboratory into the clinical arena.

The development of MR-compatible electrical conductors, coupled with the advent of molecular imaging, promises to open opportunities for interventional MRI in environments where other imaging modalities cannot be used. In other words, interventional MRI would be the only technique on offer, rather than an alternative to x-ray guidance. The three applications attracting the most interest are:
• endovascular treatment of congenital heart disease;
• electrophysiological interventions; and
• targeted delivery of drugs, cells, and/or genes for tissue repair.

TECHNICAL REQUIREMENTS

Endovascular interventions require real-time imaging. The temporal resolution should be close to that obtained with x-ray fluoroscopy so that instruments can be monitored and potential complications assessed. A frame rate of approximately six images per second is needed for safe catheter guidance.

Real-time MRI is usually obtained by combining rapid imaging strategies, such as radial or spiral techniques, that are rather insensitive to motion and fill the data space (k-space) in an efficient way, with smart reconstruction methods that increase the apparent frame rate. The sliding window technique is one of numerous ways of achieving this combination.

The two main strategies for following interventions on MRI are passive visualization, which relies on the imaging features of inserted devices, and active visualization, which makes use of small RF coils that have been integrated in the devices being tracked.

Passive visualization techniques delineate interventional devices as signal voids on bright blood images (true-FISP or FLASH sequences). Small markers made from iron particles, nitinol, or dysprosium can be added to the device to enhance visualization (Figure 2). The main advantage of this strategy is its immediate applicability. No modifications to the scanner are required, and devices made from nonconducting materials will be MR-compatible.

The main drawback of passive visualization is the need to continually interact with the imaging system. The slice position must be adjusted manually when following the catheter tip. If the end of the catheter has not been labeled clearly and has moved out of the imaging window, it could be confused with another part of the catheter shaft.

The catheter tip’s location can be detected and tracked automatically when using active visualization. This allows the slice position to be adjusted automatically too. A wire connection must be made to the scanner, though, which usually requires hardware to be modified. Another drawback is the high cost of the devices, which are disposable.

CONGENITAL HEART DISEASE

Treatment options for congenital heart disease have improved considerably over the past few decades, allowing patients to reach adulthood. A clinical examination and noninvasive imaging methods can be used together to guide treatment decisions.

Repeated cardiac catheterization procedures are required to measure physiological parameters and assess the right time for reintervention. This patient group, however, is highly vulnerable to the effects of ionizing radiation. A single fluoroscopy-guided cardiac catheterization procedure carries a one in 1000 risk of solid tumor development in children aged five years or younger.^1,2 The individual anatomy of patients with congenital heart disease is also usually highly complex, especially after palliative surgery.

Orientation on fluoroscopic images can be difficult in such cases because the anatomical structures are superimposed on each other in this projection technique and chambers cannot be directly identified due to the missing soft tissue contrast. The use of MRguided cardiac catheterization is consequently worthwhile in these patients.

A protocol for MR-guided cardiac catheterization, including calculation of pulmonary vascular resistance, has been established clinically.² Standard MRcompatible, multipurpose, nonbraided balloon catheters can be employed. The excellent soft tissue contrast and anatomical visualization afforded by MRI facilitates catheterization. MRguided diagnostic catheterization also allows flow to be measured, unlike fluoroscopy.

MR-compatible devices, including a prototype guidewire, have also been used to dilate coarctation in human subjects.³ The combination of data obtained from hemodynamic catheterization, MRI (flow and ventricular function), and delineation of anatomy beyond luminography leads to improved diagnoses and greater capacity for intervention in patients with complex congenital heart disease.

ELECTROPHYSIOLOGY

Radiofrequency ablation (RFA) is the first-line therapy for supraventricular arrhythmias. Interventions that are aimed at identifying arrhythmic substrate and ablating such foci are currently performed using a combination of x-ray fluoroscopy and electrophysiological mapping.

Ablation strategies are now shifting and anatomical targets are being identified instead of barely electrical substrates. For example, practitioners might want to ablate chunks of vital myocardium within scar tissue in the ventricles that could potentially be involved in the tachycardia circuit.

The ability of x-ray fluoroscopy to visualize anatomical structures and verify the ablating catheter’s position is rather limited, owing to the lack of soft tissue contrast. This has prompted clinicians to request an MRI or CT examination prior to the procedure so that the images can be matched with the mapping system. Results have not always been completely satisfactory, and registration errors have hampered catheter guidance.

The parallel evolution in ablation strategies, as mentioned above, has also prompted demand for an imaging modality capable of visualizing such areas while ablation is ongoing.

Real-time MRI has been suggested as a way of meeting these clinical needs. Images acquired during the procedure present the actual anatomy, rendering coregistration with fiducial markers unnecessary. Ventricular scars can be visualized in 3D so that catheter/tissue contact can be assessed directly.

MR-guided ablation requires reliable visualization of the catheter and contact recording of the intracardiac electrocardiogram (mV range) during scanning and ablation. Recording of ECG data from the endocardial surface rather than from remote locations is indispensable because the arrhythmogenic focus must be exactly identified for successful ablation.

The signal-to-noise ratio of the intracardial ECG signal can be significantly enhanced by using ECG signal filtering.⁴ RF filters and shielding can help avoid image distortion.⁵ The contact electrocardiogram obtained from the catheter tip must be coregistered reliably to its location in the cardiac chamber. This goal has been achieved through the use of active catheter tracking, whereby coordinates of signals from catheter microcoils can be superimposed simultaneously on anatomic images.⁶ Areas treated with RFA can be detected immediately on T2- weighted images and on T1-weighted images after intravenous injection of contrast.⁵

Future applications for MR-guided RFA could include the ablation of arrhythmogenic foci in patients who have congenital heart disease, such as single ventricles treated after a Fontane operation.

Another promising indication is ablation strategies aiming at anatomical structures, such as isolation of pulmonary veins. In this case, pulmonary veins are gapless and circled with ablation foci, in order to introduce a barrier for excitation pulses generated in arrhythmogenic foci in the ostium of a pulmonary vein. MRI guidance will decrease the time taken for intervention. This should reduce the overall number of complications, which has been shown to correlate with lengthy procedures. MR-compatible ablation systems are currently being developed. The development of safe conductors for intracardial ECG mapping and ablation are key to the success of all MR-guided electrophysiological procedures.

THERAPY DELIVERY

Different strategies in development for local therapy delivery are likely to culminate in a concept that can be realized exclusively with interventional MRI.

Revascularization therapy for coronary artery occlusion has matured over several decades. Bypass operations and stent placement are performed widely and to a high standard. The long-term morbidity of patients with myocardial infarction remains low, however, owing to the remodeling of the left ventricle. Therapeutic efforts have consequently focused on the reduction of scar tissue after myocardial infarction.

Clinical studies have shown that intramyocardial injection of stem cells, collected previously from the patient, can improve global left ventricular function. ⁷ This strategy works by increasing the quantity of contractile myocytes and/or supplying capillaries. Stem cell injection is typically carried out during bypass surgery.

A catheter-based approach for the injection of cells or genes is an appealing solution. This would allow repeated injections rather than the single-shot approach currently employed during surgery. The modality used for image guidance should be able to delineate the target area (the myocardial infarction site), visualize the catheter, and depict the distribution of the injected material.

Fluoroscopy and ultrasound can each fulfill one of these criteria, whereas MRI is capable of all three.^8-10 The injected substance must be labeled prior to intravenous administration. Fluids are commonly doped with extracellular contrast media,⁹ while cells have been labeled with ultrasmall iron oxide particles.8 USPIO-tagged cells can be followed up on MRI even weeks after the initial injection.¹¹

Another indication for MR-guided therapy delivery is the application of drugs to vessel walls during angioplasty of peripheral arteries. Delivery of such agents has been shown to reduce postangioplasty restenosis significantly.¹²

An animal study dilated peripheral vascular stenoses while a solution containing MR contrast medium and Evans blue dye (a tissue dye) was applied to the vessel wall.¹³ Distribution of the contrast medium in the vessel wall was visible on MRI (Figure 3) and resembled that of the tissue dye as seen on autopsy, facilitating assessment of the delivery location.

MRI will be used in the future to characterize plaque and then monitor delivery of whichever therapeutic agent was indicated by the imaging results in the vessel wall. Such a therapy is not possible under x-ray guidance because the vessel wall cannot be delineated well enough.

MRI has been used in preclinical studies to guide the injection of pancreatic islet cells, immunoisolated by encapsulation in magnetocapsules, into the portal vein.¹⁴ The extent of engraftment of the magnetocapsules into the liver could potentially be monitored over time with MR. Such an approach would be valuable for the treatment of patients with type I diabetes.

HIGH FIELD BENEFITS

Raising the MRI field strength to 3T would increase the signal-tonoise ratio, which in turn could be invested in higher spatial resolution. This could be advantageous for vessel wall imaging. Better delineation and characterization of plaque components may aid decision-making when faced with alternative therapeutic options, dilatation with or without local delivery of drugs or stent placement, for example.

Initial animal studies have already shown the feasibility of performing endovascular interventions at 3T (Figure 4). The combination of molecular imaging with interventional MRI, to guide the local delivery of labeled substances to selectively marked targets, for example, is a highly promising direction. Molecular imaging has a higher sensitivity at high field strengths due to the SNR gain.

Devices that are MR-safe at 1.5T must be reevaluated if they are to be used with a 3T system. This is particularly important for any devices containing metal.¹⁵