Progress in PAD: Where MR Steps In

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occluded-SFA-cropped.jpg - occluded-SFA-cropped
Contrast-enhanced magnetic resonance angiogram (MRA) shows a segment of irregular severe narrowing in the distal right superficial femoral artery (green arrow) and complete occlusion of the left superficial femoral artery (green arrow). Multiple large and small collateral vessels (blue arrow) reconstitute the left superficial femoral artery at the level of the adductor canal.
Source: J Am Coll Cardiol Img 2013; 6:687-694

In the assessment of peripheral artery disease (PAD), the initial test requires only a blood pressure cuff and CT angiography (CTA) to noninvasively image small vessels. This would seem to leave MRI to play a bit part, but as techniques improve, MR’s role in both clinical use and research grows more important.

PAD is characterized by blockages in blood vessels in the lower extremities caused by atherosclerosis. More than 200 million people worldwide suffered from the condition in 2010, a number that rose by 23.5 percent in the previous decade (The Lancet online Aug. 1, 2013). Low- and middle-income countries demonstrate the greatest PAD burden, but the condition still affects approximately 8 million patients in the U.S. While interventions can reintroduce blood flow to the legs, tens of thousands of people still must undergo amputations.

For most patients, pain in the lower extremities that could be symptomatic of PAD is first evaluated by ankle-brachial index testing. This simple test compares blood pressure in the feet to blood pressure in the arm, and in cases of PAD, ankle pressure.

Imaging becomes more important when patients are candidates for revascularization through stent or surgery, and digital subtraction angiography (DSA) and CTA lead as the imaging modalities for evaluating PAD. Cassidy Duran, MD, of Methodist DeBakey Heart & Vascular Center in the Methodist Hospital in Houston, says a prejudice developed against MR angiography (MRA) because of the limitation of the traditional 2D time-of-flight technique. Since it is dependent on flow to capture the image, time-of-flight MRA tends to overestimate stenosis in patients with reduced flow.

“When you’re imaging a patient who may have very poor velocities down in the runoff vessels to the feet, it all breaks down and you don’t know what to make of it,” says Duran.

Enter contrast-enhancement with gadolinium, which cardiologists at Duran’s institution use to perform 3D MRA in PAD patients. “Initially there was a lot of excitement about MR and gadolinium because it allowed you to get a contrast enhanced image in a patient whose kidneys made them not a good candidate for receiving iodinated contrast,” she says.

But gadolinium cannot circumvent all the roadblocks related to kidney function. While it does not cause contrast-induced nephropathy like iodinated contrast, exposure to gadolinium can result in a separate, but still painful and debilitating syndrome, nephrogenic systemic fibrosis (NSF). This prompted Duran and colleagues to look for another alternative for patients at-risk for NSF. What they found was Feraheme, an FDA-approved drug for the intravenous treatment of iron deficiency anemia in chronic kidney disease patients. Feraheme’s molecular structure also makes it useful as an imaging agent, though this is currently an off-label use. Duran and colleagues found Feraheme works as well as gadolinium for imaging peripheral vasculature, and she expects the FDA to approve it as an agent soon, speeding its further adoption.

Contrasting techniques

Aside from Feraheme, another contrast agent making waves is gadofosveset, a blood pool agent. Whereas standard contrast agents are extracellular and are removed by the kidneys, gadofosveset binds to the protein albumin and remains in the intravascular space, explains James Carr, MD, of the Department of Radiology at Northwestern University-Feinberg School of Medicine in Chicago.“Because it’s bound to albumin, the contrast agent circulates for a prolonged period of time, therefore you get the effect of the contrast agent for much longer than you would get with a standard agent,” says Carr.

The intravascular half-life of gadofosveset is up to 60 minutes and this extended period of time allows for images with increased spatial resolution. Limited spatial resolution was one of the drawbacks of MRA compared with CTA, notes Carr.

In an article reviewing the use of gadofosveset, Carr and colleagues wrote that MRA performed using gadofosveset with both a first-pass (which includes the abdomen, pelvis and thighs) and equilibrium phase five to 10 minutes after contrast injection yielded a sensitivity and specificity of 97 percent for detection of significant disease in the lower extremities (J Vasc Surg 2013;57:837-841).

Noncontrast MRA is currently flexing its muscle in trials and ECG-gated quiescent-interval single-shot (QISS) MRA is a promising new technique that has nearly equal efficacy to contrast enhanced MRA, says Carr.