PREVALENCE AND EPIDEMIOLOGY

Atherosclerotic PAD is an important health care problem in Western society, with an estimated prevalence of about 3% of the general population in those older than 50 years. The prevalence rises to about 15% to 20% of the general population in those older than 70 years.¹

ETIOLOGY AND PATHOPHYSIOLOGY

Patients with PAD typically present with a history of intermittent claudication. This term is derived from the Latin claudicatio, which means to limp. Claudication typically consists of cramping and pain in the buttocks, thighs, and lower legs that occurs with exercise (e.g. walking or climbing stairs). In these symptomatic patients with PAD, peripheral arterial blood flow is unable to augment to meet the increased metabolic demands of the lower extremity muscles during exercise. On cessation of exercise, these complaints typically disappear rapidly because arterial flow at rest is typically sufficient to meet the patient’s basal metabolic needs.

In a minority of patients with intermittent claudication, the PAD will subsequently progress to critical ischemia, whereby even at rest the lower extremity arterial flow is insufficient to meet basal resting metabolic needs (i.e., oxygen and nutrient demand) of the lower extremity. Clinically, this is manifested by pain at rest and, in more severe cases, as nonhealing ulcers, cellulitis, and even gangrene. See Chapter 113 for an extensive discussion of the clinical aspects of PAD.

MANIFESTATIONS OF DISEASE

Clinical Presentation

The diagnosis of PAD is made on the basis of the typical history, physical examination (palpation of arterial pulsations), and measurement of the ABI. When a patient presents to the general practitioner or vascular surgeon with complaints of PAD, first-line treatment consists of modification of and/or treatment for atherosclerotic risk factors, such as smoking, hypertension, hypercholesterolemia, and the institution of (supervised) exercise training.²^,³ Only when the patient’s complaints become too limiting to pursue regular activities will invasive interventional treatments be considered. For patients with intermittent claudication, the decision to intervene is largely dependent on relative criteria (patient and surgeon preference), but for patients with chronic critical ischemia, the need to intervene is more urgent because tissue perfusion does not meet basic metabolic demands, even at rest. Of 100 patients presenting with PAD, 5 eventually undergo percutaneous or surgical treatment.¹ Although this is only a small minority of patients with PAD, the estimated annual number of percutaneous and surgical procedures performed for PAD in the United States alone was well over 200,000 in 2000, with sharp increases expected.⁴

Imaging Indications and Algorithm

Because the diagnosis of PAD is usually made from the typical history, physical examination, and ABI measurements, the need for imaging of the peripheral arteries only arises when a percutaneous or surgical intervention is considered. Imaging is needed to explore the extent of the disease process (e.g., number, location, and severity of atherosclerotic lesions) and to plan the correct approach for therapy.⁵

Traditionally, the standard of reference for imaging PAD has been x-ray catheter angiography, which initially had been through a translumbar aortic approach. In 1953, the transfemoral approach was developed by Seldinger, in which arterial access is gained through the superficial or common femoral artery.⁶ Having been refined and technically optimized, this is the procedure most widely used in state of the art angiography today, and is still considered the standard of reference. When combined with digital subtraction techniques, high-resolution projection arteriograms of the peripheral arterial circulation can be obtained in a routine fashion. However, substantial rates of local and systemic procedure-related complications have sparked the search for noninvasive alternatives to IA DSA.

Patients with PAD are best served when they undergo as little testing as possible to establish a diagnosis and plan the appropriate therapy. The key clinical question is whether patients are candidates for a simple local procedure (e.g., percutaneous transluminal angioplasty or local endarterectomy) to treat focal disease or, alternatively, whether the disease is too diffuse and long segmented so that it requires a more extensive or complex procedure such as aortofemoral bypass surgery. CE MRA is well-suited for this purpose and can serve as the primary imaging modality for patients with PAD because it provides the necessary information for proper diagnosis and procedural decision making.

Imaging Techniques and Findings

Radiography

Conventional radiographs may demonstrate calcific deposits in the vessel wall but, in general, there is no role for dedicated radiography in the assessment of suspected peripheral arterial disease.

Ultrasound

DUS is widely used to determine the location, length, and severity of aortoiliac and femoropopliteal stenoses and obstructions. Duplex ultrasound was developed in the 1980s as an alternative to invasive angiography to avoid the inherent complications associated with the latter procedure. With DUS, the severity of a stenosis can be determined by using peak systolic velocity (PSV) measurements in arteries with reduced luminal diameter, PSV ratio at the site of stenosis and adjacent normal artery, end-diastolic velocity, and other less firmly established criteria. The sensitivity and specificity of DUS are generally moderate to high, ranging from 70% to 90%.⁷ However, a relatively recent meta-analysis,⁸ as well as a large prospective comparison study between CE MRA and DUS in 295 patients,⁹ has found that CE MRA is more sensitive and specific compared with DUS for the detection of PAD.

Computed Tomography

Recent advances in CT technology have enabled fast and robust CT angiography (CTA) of the peripheral vascular tree. Although there are fewer reports comparing CTA with conventional angiography for the detection of PAD as compared with CE MRA, it is widely believed that CTA is a valid and reliable method.¹⁰ The drawback of CTA is the enormous number of data sets that it generates—up to several thousand images per patient—and that heavily calcified arteries demand extensive user interaction to assess the underlying degree of stenosis adequately. In addition, the newest generation of multidetector row CT scanners is so fast that the contrast bolus may progress more slowly down the leg than the CT acquisition, leading to suboptimal opacification of the distal lower extremity arteries. For an in-depth discussion of CTA of the peripheral arteries, including these issues, see Chapter 115.

Magnetic Resonance Angiography

Although there are a variety of different MR angiography techniques, CE MRA is the most widely used method. Phase contrast (PC) and time of flight (TOF) MRA ¹¹ were the subjects of intense investigation about a decade ago, but the intrinsic drawbacks associated with these methods, such as long imaging times and their propensity to overestimate the degree and length of arterial stenoses, have led to the abandonment of these techniques in favor of CE MRA. The superiority of CE MRA over other MRA methods for peripheral artery imaging has been confirmed in several meta-analyses.¹²^,¹³

Recent concerns related to nephrogenic systemic fibrosis (NSF) have resulted in an increased interest in noncontrast-enhanced balanced steady-state free precession (bSSFP)–based techniques as alternatives for CE MRA. Although these techniques are promising, there are very limited data with regard to their diagnostic accuracy and clinical utility for imaging patients with PAD. Preliminary data have indicated that the value of these techniques lies in their high negative predictive value.

Contrast-Enhanced Magnetic Resonance Angiography of the Peripheral Arteries

The challenge for imaging patients with PAD is the need for imaging over an extended field of view (FOV) that begins at least from the level of the aortic bifurcation to the distal runoff vessels (ankles, feet), a region that typically requires imaging over three overlapping FOVs (abdomen-pelvis, thighs, and calves-feet). Current CE MRA techniques using some combination of bolus chase or stepping table CE MRA can usually cover the peripheral arterial tree within 15 minutes. However, adequate planning of peripheral CE MRA is essential. Operators must not only ensure proper anatomic coverage of the overlapping three-dimensional MRA volumes but also adjust the various imaging parameters to provide high image quality and spatial resolution for optimal benefit of the arterial phase of the contrast medium bolus. The exact spatial location of the three-dimensional CE MRA imaging volumes that cover the vascular tree of interest is determined on scout or localizer images. Scout scans are usually axial, thick-slice, low-resolution two-dimensional TOF scans or, more recently, steady-state free precession (SSFP) acquisitions. Acquisition of scout views in a sagittal or coronal orientation can also be useful. The advantage of using two-dimensional TOF images is that the vascular anatomy can be selectively viewed on postprocessed maximum intensity projections (MIPs). When the three-dimensional CE MRA volumes are prescribed, transverse source images should always be reviewed to ensure that all relevant vascular structures are included in the imaging volume. Failure to do so can result in the exclusion of relevant anatomy from the imaging volume.

Vascular Anatomy Considerations

In most patients, the anteroposterior coverage needed is usually less than 10 cm. When imaging in the presence of an aortic aneurysm, iliac arterial elongation, collateral bridging iliac or superficial femoral arterial obstructions, or femorofemoral crossover bypass graft, the anteroposterior (AP) coverage needed to depict these vessels may be markedly increased (up to 15 to 20 cm). Review of the transverse localizer images ensures that these structures are not excluded from the three-dimensional CE MRA imaging volume. This is particularly important if a patient has a femorofemoral crossover bypass graft because these grafts are usually not seen on axial TOF MIPs because of in-plane saturation artifacts. Particular attention should be paid to prescription of the MRA imaging volumes in patients with extra-anatomic bypass grafts because the grafts often extend beyond the traditional boundaries of a routine peripheral CE MRA and the scan volumes will need to be modified to include the grafts. Other patients that demand special attention are those with (thoraco-)abdominal aortic aneurysms in whom flow may be markedly slower compared with patients without an aortic aneurysm. If the scan delay (i.e., time period between the initiation of the contrast bolus injection and the beginning of MRI) is too short, there will be incomplete opacification of the abdominal aorta and its branches. This problem can be solved by use of a longer scan delay or a multiphase MRA acquisition technique (i.e., time-resolved MRA).

Synchronization of Three-Dimensional Contrast-Enhanced Magnetic Resonance Angiography Acquisition with Contrast Arrival

For successful CE MRA, care must be taken to synchronize peak arterial enhancement with image data acquisition, specifically acquisition of the central k-space data. The time of peak arterial enhancement is a function of many variables, the most important of which are injection rate and volume, amount and rate of saline flush,¹⁴ and cardiac output.¹⁵ Because the time of peak arterial enhancement can vary substantially among patients, the CE MRA examination needs to be tailored to the individual contrast arrival time. This is important for two main reasons: (1) to prevent “ringing” image artifacts and poor arterial opacification, which may occur if imaging is performed too early; and (2) to prevent suboptimal arterial enhancement and excessive venous and/or background enhancement, which occurs if imaging is performed too late.

To ensure acquisition of central k-space views during peak arterial enhancement, a two-dimensional time-resolved test bolus technique can be used. More recently, real-time bolus monitoring software packages have been introduced by all major MRI system vendors, and these are now considered the state of the art for CE MRA (e.g., BolusTrak, Philips Medical Systems, Best, The Netherlands; CareBolus, Siemens Medical Solutions, Erlangen, Germany; and Fluoro Trigger, General Electric Healthcare, Waukesha, Wisc). Instead of injecting a small amount of contrast material in a separate test bolus scan, real-time bolus monitoring allows the operator to time the imaging for the CE MRA in real time using a single contrast injection of the total volume of contrast material. Using real-time bolus monitoring, the operator monitors the contrast bolus progression and initiates MRA scanning when the desired signal enhancement in the target arterial bed has been reached. Automated bolus detection algorithms that do not require operator initiation of scanning are also available and are equally successful for achieving proper CE MRA timing.

Strategies to Optimize Vessel to Background Contrast

For multistation peripheral CE MRA (i.e., bolus chase CE MRA), the arterial T1 shortening associated with the sustained injection of a 0.1- to 0.3-mmol/kg dose of a standard (0.5 M) gadolinium-chelate contrast agent is generally insufficient to view the arteries preferentially over the extended FOVs over that of background tissue, especially in distal infrapopliteal arteries. The elimination of signal from background tissues, especially fat, because it has the shortest T1, is typically necessary for successful multistation peripheral CE MRA. The most commonly used technique to suppress background signal is image subtraction of nonenhanced mask three-dimensional MRA images from those of similarly acquired contrast-enhanced three-dimensional CE MRA. Although image subtraction decreases the signal-to-noise ratio by a factor of about 1.4 (v2 when the number of signals acquired is 1), vessel to background contrast improves to the extent that whole-volume MIPs become clinically useful, especially when using injection rates below 1.0 mL/sec.¹⁶ A disadvantage of using mask scans is that patients may move in between acquisition of the mask and contrast-enhanced parts of the scan, which can lead to subtraction misregistration artifacts. Subtraction misregistration artifacts may also occur if table positioning between the precontrast mask and postcontrast CE MRA is not accurate, on the order of 1 mm or less.

Because the T1 of fat is close to that of contrast-enhanced arterial blood, another way to suppress background tissue is by spectral saturation of signal from protons in fat. Although a fat saturation prepulse can be integrated into the three-dimensional CE MRA sequence, this takes a significant amount of time, which in turn must be offset by decreasing spatial resolution to achieve the same desired overall acquisition duration. Results of using fat saturation pulses are mixed and their use can, therefore, not be universally recommended.¹⁷^,¹⁸

A dedicated peripheral vascular surface coil is mandatory for high-quality imaging of the pelvic and lower leg arteries. Image quality and anatomic coverage are vastly improved when compared with imaging without these dedicated lower extremity coils.¹⁹

Strategies to Decrease Venous Enhancement

Venous contamination is an important problem for CE MRA. This problem is particularly prevalent in patients with cellulitis or arteriovenous fistulas or malformations.²⁰ Venous and background soft tissue contamination of arterial illustration are particularly prevalent in patients with diabetes mellitus.²¹ Diabetic patients, furthermore, are more likely to have limb-threatening ischemia and to require peripheral distal bypass surgery, making them prime candidates for preoperative peripheral artery imaging using CE MRA.

The most straightforward way of preventing venous enhancement is by shortening the MRA acquisition duration. This should be done, first of all, by lowering the repetition time (TR) and echo time (TE) to the shortest possible value, without excessively increasing bandwidth. In addition, partial Fourier or fractional echo imaging can be used. When doing peripheral CE MRA (i.e., bolus chase CE MRA using three consecutive overlapping stations), it is particularly important to image the proximal two stations (aortoiliac and upper legs) as fast as possible. This affords a relatively longer scan period for high spatial resolution imaging of the smaller distal lower extremity (infrapopliteal) arteries. Use of centric or elliptical centric k-space filling schemes for this third and terminal station minimizes venous enhancement, despite the lateness of imaging relative to the overall contrast bolus duration. With the introduction of multielement surface coils, whereby multiple reception coils are used simultaneously to collect data, acquisition speed can be increased further by applying parallel imaging algorithms.

To avoid the limitations of imaging three consecutive stations, an alternative approach is to use two separate injections for peripheral CE MRA. In this approach, the distal lower legs (calves-feet or infrapopliteal region) are imaged during the first contrast medium bolus, and then a second contrast medium injection is administered to image the remaining two more proximal stations (the aortoiliac region and upper legs) using a two-station bolus chase CE MRA method. A benefit of this hybrid approach ²²

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