The vast majority (>80%) of lower extremity arterial disease is due to atherosclerotic peripheral arterial occlusive disease (APAOD). APAOD is a major health care problem in Western society with an estimated prevalence in the general population of 2.5% in persons over 50 years of age. In persons over 70 years of age, the prevalence is estimated at about 7% (1).

Patients who have complaints of APAOD usually present with a history of intermittent claudication. This term is derived from the Latin claudicatio and means “to limp.” Intermittent claudication is caused when blood flow to exercising leg and calf muscles is insufficient compared to metabolic demands. Significant disease in the aortoiliac arteries (Fig. 21-1) typically leads to cramping and pain in buttocks and thighs, while more distally located disease (e.g., tibioperoneal occlusive disease) is often associated with cramping in the foot. Upon cessation of exercise, complaints usually disappear rapidly. The clinical course of intermittent claudication in terms of progression of disease in the symptomatic limb is usually benign since only about a quarter of patients will ever significantly deteriorate (1). With an intervention rate of approximately 5%, only 1% to 3% of all patients with intermittent claudication will ever undergo a major amputation (1).

About 5% or less of patients with intermittent claudication progress to chronic critical ischemia, that is, the oxygen and nutrient supply of the distal lower extremity fall below the level for maintenance of normal cellular processes in resting conditions. Clinically, this is manifested by rest pain and tissue loss (i.e., nonhealing ulcers and gangrene).

The incidence of chronic critical ischemia is estimated to be between 300 and 1,000 per million per year in the general population (1). Because of the severity of complaints, an invasive intervention is attempted in all but the worst cases. Despite advances in endovascular and vascular surgical therapy, however, the rate of major amputation in the general population remains in excess of 0.03% in industrialized countries (2).

The diagnosis of APAOD is made on the basis of the typical history, physical examination (palpation of arterial pulsations), and measurement of the ankle-brachial index (ABI) (1,3). The severity of APAOD is commonly classified according to Fontaine (Table 21-1). More recently, the Society for Vascular Surgery and the International Society for Cardiovascular Surgery introduced a classification, named after Rutherford, that also incorporates hemodynamic and performance criteria (4) (Table 21-2).

When a patient presents to the general practitioner or the vascular surgeon with complaints of APAOD, the first-line treatment consists of modification of obvious cardiovascular risk factors such as smoking, hypertension, hypercholesterolemia, and the institution of exercise training (5,6,7). Generally, options for invasive intervention are considered when complaints become too limiting to pursue ordinary activities.

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 since tissue perfusion does not meet basic metabolic demands, even at rest.

Although only a small minority of patients with APAOD eventually undergo invasive treatment, the estimated annual number of percutaneous and surgical procedures performed for PAOD in the United States alone was over 100,000 in 1986, with sharp increases expected (8), illustrating the large scope of the problem and impact on people’s lives.

In contrast to the gradual course of disease perceived with intermittent claudication and chronic critical ischemia is the entity of acute limb ischemia. Acute limb ischemia denotes a sudden and rapid decline in limb perfusion, usually producing new or worsening signs and symptoms; often, limb viability is threatened. In patients with APAOD, acute limb ischemia is most often caused by either an embolus or thrombosis. The severity of acute limb ischemia depends on the location and extent of occlusion and the degree to which pre-existing collaterals can be recruited (1).

Approximately 20% of chronic arterial occlusions are based on diseases other than atherosclerosis that cause luminal narrowing and/or occlusion. The presence, location, and progression of arterial stenoses and occlusions may reflect an underlying systemic disease or may be an expression of regional inflammatory or degenerative processes.

Lower extremity arterial diseases other than APAOD include aneurysmal disease, popliteal entrapment syndrome, cystic adventitial disease, arterial fibrodysplasia, nonspecific aortoarteritis (Takayasu disease), and a host of uncommon vasculitides, the most important of which is thromboangiitis obliterans (Buerger’s disease) (9). In addition, congenital connective tissue diseases such as Marfan syndrome, Ehlers-Danlos syndrome, pseudoxanthoma elasticum, homocystinuria, and neurofibromatosis may have peripheral arterial involvement.

Congenital and acquired clotting disorders may also manifest themselves with symptoms of peripheral arterial disease. Rare causes of peripheral arterial disease are primary tumors, radiation therapy, and the iliac syndrome in cyclists. An acute arterial occlusion always necessitates a prompt search for atrial fibrillation, ulcerative endocarditis, and mural thrombi overlying the site of myocardial infarction.

Peripheral CT angiograms can be obtained with any MDCT scanner (4-channel and above). No special hardware is required. With a standardized scanning protocol programmed into the scanner, peripheral CTA is a robust technique for elective and emergency situations. When patients are mobile, the study can easily be performed in 10 to 15 minutes of room time. The short acquisition time of 25 to 50 seconds makes it possible to scan acutely ill patients (e.g., in the emergency room setting) as well.

In general, peripheral CTA acquisition parameters follow those of abdominal CTA. Unless automated tube-current modulation is available (which is strongly recommended), a tube voltage of 120 kV and tube amperage of up to 300 mA (depending on the scanner) is used for peripheral CTA, which results in a similar radiation exposure and dose (12.97 mGy, 9.3 mSv) as abdominal CTA (24). Breath holding is required only at the beginning of the CT acquisition through the abdomen and pelvis. Lower amperage (and/or voltage) can and should be used in slim patients. In obese patients, tube voltage and tube current often need to be increased. A medium to small imaging field-of-view (FOV) (using the greater trochanter as a bony landmark) and a medium-soft reconstruction kernel are generally used for image reconstruction.

One (or more) dedicated “peripheral CTA” acquisition and contrast medium injection protocol(s) should be established for each scanner and programmed into the scanner. A full scanning protocol consists of (a) the digital radiograph (“Scout” or “Topogram”); (b) an optional nonenhanced acquisition; (c) one series for a test bolus or bolus triggering; (d) the actual CTA series; and (e) a second, optional (“late phase”) CTA acquisition (only initiated on demand) in the event of nonopacification of distal vessels (Fig. 21-2).

The patient is placed feet first and supine on the couch of the scanner. In order to keep the image reconstruction FOV small, and also to avoid off-center stair-step artifacts (32), it is important to carefully align the patient’s legs and feet close
to the isocenter of the scanner. Tape may be required to hold a patient’s knees together. While cushions can be used to stabilize the extremities to the patient’s comfort, large cushions under the knees should not be used to keep the FOV small.

Also—as in conventional angiography—excessive plantar-flexion of the feet is avoided to prevent an artifactual stenosis or occlusion of the dorsalis pedis artery (“ballerina sign”) (33). The standard anatomic coverage extends from the T12 vertebral body level (to include the renal artery origins) proximally through the patient’s feet distally (Fig. 21-2). The average scan length is between 110 and 130 cm. Smaller scan ranges (e.g., mid-thigh to feet) or a smaller FOV (one leg only) may be selected in specific clinical situations, such as in popliteal arterial entrapment syndrome, or trauma.

In patients with suspected popliteal arterial entrapment syndrome, we use a sling of bedsheet under the patient’s forefoot to allow for a provocation maneuver with contraction of the calf muscles against the sheet, which is pulled by the patient during the scan time (Fig. 21-3). Two contrast medium injections (80 mL each) and three CT acquisitions (arterial phase with provocation for the first injection, arterial and venous phases for the second injection, respectively) are given.

The choice of acquisition parameters (detector configuration/pitch) and the corresponding reconstruction parameters (section thickness/reconstruction interval) depends largely on the type and model of the scanner. Table 21-4 provides an overview of peripheral CTA acquisition parameters for a wide range of MDCT scanners and reflects our clinical
experience with 4-, 16-, and 64-channel Siemens MDCT scanners (Siemens Medical Solutions, Erlangen, Germany), and 4-, 8,- and 16-channel General Electric MDCT scanners (General Electric Healthcare, Milwaukee, WI). Detector configuration is denoted as number of channels times channel width (e.g., 4 ÷ 2.5 mm); section thickness (STh) and reconstruction interval (RI) are expressed as STh/RI (e.g., 3 mm/1.5 mm).

The time interval between the beginning of the intravenous contrast medium injection and the arrival of the bolus in the aorta—referred to as the contrast medium transit time (t_CMT)—is very variable between patients with coexisting cardiocirculatory disease and may range from 12 to 40 seconds. Individualizing the scanning delay is thus generally recommended in peripheral CTA. A patient’s individual t_CMT can be reliably determined with a small test-bolus injection or estimated by using automated bolus-triggering techniques. The scanning delay may then be chosen to equal the t_CMT (the scan is thus initiated as soon as contrast medium arrives in the aorta), or the scanning delay may be chosen at a predefined interval after the t_CMT. For example, the notation “t_CMT + 5s” means that the scan starts 5 seconds after contrast medium has arrived in the aorta.

The additional challenge in patients with PAOD is related to the well-known fact that arterial stenoses, occlusions, or aneurysms anywhere between the infrarenal abdominal aorta and the pedal arteries may substantially delay downstream vascular opacification (36,37). More specifically, in a group of 20 patients with PAOD, it was found that the transit times of IV-injected contrast medium to travel from the aorta to the popliteal arteries ranged from 4 to 24 seconds (average: 10 seconds), which corresponds to bolus transit speeds as fast as 177 mm/second to as slow as 29 mm/second, respectively (38).

The clinical implication for peripheral CTA is that when a table speed of ∼30 mm/second is selected, it is very unlikely (though not impossible) that the data acquisition is faster than the intravascular contrast medium bolus. With increasing acquisition speeds, however, the scanner table may move faster than the intravascular contrast medium column, and the scanner may thus outrun the bolus (Fig. 21-7). Of note, “outrunning-the-bolus” has only been reported in one study, which used a table speed of 37 mm/second (26),
but it has not been reported in five other published studies on peripheral CTA, all of which used table speeds of 19 to 30 mm/second (24,25,27,28,39).

For the following discussion, it is thus useful to arbitrarily categorize injection strategies for peripheral CTA into those for “slow” acquisitions (≤30 mm/second table speed) and those for “fast” acquisitions (>30 mm/second table speed). Sixty-four-channel MDCT injection strategies will be discussed separately.

Detector configuration settings of 4 ÷ 2.5 mm, 8 ÷ 1.25 mm, and 16 ÷ 0.625 mm all translate into an acquisition speed of approximately 30 mm/second. Such a table speed usually translates into a scan time of approximately 40 seconds for the entire peripheral arterial tree. Because the data acquisition follows the bolus from the aorta down to the feet, the injection duration can be chosen approximately 5 seconds shorter than the scan time. For example, for a 40-second acquisition, a 35-second injection duration is sufficient. This would translate into 140 mL of contrast medium if a constant injection rate of 4 mL/second was used. If the beginning of the data acquisition is timed closely to the contrast arrival time in the aorta (using a test bolus or bolus triggering), biphasic injections achieve more favorable enhancement profiles, with improved aortic enhancement. As an example, our current protocol for a submillimeter acquisition with a Siemens 16-channel scanner is shown in Table 21-5). A similar concept is used for the 64-channel Siemens scanner at our institution as well.

Detector configuration settings of 8 ÷ 2.5, 16 ÷ 1.25, or 16 ÷ 1.5 translate into acquisition speeds of 45 to 65 mm/second, which—in some individuals—may be faster than the contrast medium bolus travels through a diseased peripheral arterial tree. In order to prevent the CT acquisition to outrun the bolus, it is necessary to allow the bolus a “head start.” This is accomplished by combining a fixed injection duration of 35 seconds to fill the arterial tree and a delay of the start of the CT acquisition relative to the time of contrast medium arrival in the aorta (t_CMT). The faster the acquisition, the longer this “diagnostic delay” should be chosen. We use such a strategy with a GE 16-channel scanner with a 16 ÷ 1.25 mm protocol, pitch 1.375, and
0.6-second gantry rotation period (table speed: 45mm/second). The protocol as well as its generalization to other “fast” acquisitions is shown in Table 21-6. An example of arterial opacification using this approach by using fast scans is shown in Figure 21-5. The limitation of using a very long “diagnostic delay” (>15 seconds between contrast medium arrival and scan initiation) is undesirable opacification of the renal and portal veins and the inferior vena cava.

While 32-, 40-, and 64-channel CT systems theoretically allow acquisition speeds of 80 mm/second and more, we deliberately acquire our peripheral CT angiograms at a much slower pace, by prescribing a fixed scan time of 40 seconds for each scan. For a 40-second scan time, we select a gantry rotation of 0.5 seconds and a pitch <1. Automated tube-current modulation is used in this setting to avoid increased radiation dose and also to control image noise (within and across patients). The advantage of always selecting the same 40-second scan time is that it can be combined with fixed (biphasic) injections of 35 seconds duration. The injection flow rates and volumes are then individualized to patient weight, such as shown in Table 21-7. Examples of image quality and opacification are shown in Figure 21-6.

All of the above acquisition and contrast medium injection strategies reduce the risk of outrunning the bolus but do not eliminate it. An example of a patient with extremely delayed flow, most likely caused by decreased cardiac output and altered flow dynamics due to his bilateral iliac and popliteal artery aneurysms, and diffuse arteriomegaly is demonstrated in Figure 21-8. The risk of obtaining nondiagnostic studies is addressed by preprogramming a second CTA acquisition (covering the popliteal and infrapopliteal vasculature) into the scanning protocol. This acquisition is initiated by the CT technologist immediately following the main CTA acquisition only if he or she does not see any contrast medium opacification in the distal vessels.

The above injection strategies combine individual scan timing (using bolus tracking/test-bolus) in the aorta, with empiric (non-individualized) parameter selection to adjust for a broad range of possible bolus transit speeds down to the feet. Other approaches—using more or less individualization—are also possible. For example, protocols with a fixed, long scanning delay (28s) have been used successfully in the past, notably before automated bolus tracking technique was available on the first 4-channel scanners (28).

On the other end of the spectrum are attempts to individualize both the scanning delay and the scanning speed based on both aortic and the popliteal transit times, determined individually with two test boluses (40). All of the above injection protocols can also be used in patients without occlusive disease, but deliberately delaying the scan or slowing down the acquisition is not imperative in this setting. For example, two small injections (60 to 80 mL/ second) with short scan times (5 to 6 seconds) for the two arterial acquisitions in popliteal entrapment syndrome are sufficient.

Opacification of deep and superficial veins can be observed in peripheral CTA (24) and is more likely to occur with longer scan times and in patients with active inflammation (e.g., from infected or nonhealing ulcers). Given the rapid arteriovenous transit times observed angiographically in some patients (41), venous opacification cannot be completely avoided. As arterial enhancement is always stronger than venous enhancement when the injection is timed correctly (24), and with adequate anatomic knowledge and postprocessing tools, venous enhancement rarely poses a diagnostic problem.

Reviewing of transverse CT slices is mandatory for the assessment of extravascular abdominal or pelvic pathology. This is facilitated by reconstructing an additional series of contiguous 5-mm thick sections through the abdomen and pelvis. Browsing through the stack of source images is also helpful to gain a first impression on vascular abnormalities, and in select cases—such as in patients with only minimal or no disease, in patients with trauma, or in patients with suspected acute occlusions, source image viewing may be sufficient. Relevant extravascular anatomy, such as the course and position of the medial head of the gastrocnemius muscle in popliteal entrapment syndrome, is readily depicted on the axial images and often inapparent on projection (e.g., MIP) images. Source images may also serve as a reference when 2D- or 3D-reformatted images suggest artifactual lesions. For the majority of cases with vascular disease, however, transverse image viewing is both inefficient and less accurate (27) than viewing reformatted images.

Vascular abnormalities have to be interpreted in the context of a patient’s symptoms, stage of disease, and with respect to the available treatment options. For those familiar to reading
conventional angiograms, the clinical aspect of interpreting a peripheral CTA is usually straightforward. However, visual perception and interpretation of well-known abnormalities in a new and different format (such as VR or CPR images) requires adaptation and familiarity with the specific techniques used.

Probably the most important pitfall related to the interpretation of peripheral CT angiograms is related to using narrow viewing window settings in the presence of arterial wall calcifications or stents. Even at wider-than-normal “CT-angiographic” window settings (Window level/width: 150 Hounsfield units [HU]/600 HU), high-attenuation objects (calcified plaque, stents) appear larger than they really are (“blooming”—due to the point-spread-function of the scanner), which may lead to an overestimation of a vascular stenosis or suggest a spurious occlusion.

When scrutinizing a calcified lesion or a stented segment by using any of the cross-sectional grayscale images (transverse source images, MPR, or CPR), a viewing window width of at least 1500 HU may be required (Fig. 21-9). Interactive window adjustment on a PACS viewing station or on a 3D workstation are most effective because when printed on film, window settings are usually too narrow.

In the setting of extensive atherosclerotic or media calcification within small crural or pedal arteries, such as those found in diabetic patients and in patients with end-stage renal disease, the lumen may not be resolved regardless of the window/level selection. In these circumstances,
other imaging techniques, notably MRI, may be preferable to CTA.

Other interpretation pitfalls result from misinterpretation of editing artifacts (inadvertent vessel removal) in MIP images and pseudostenosis and/or occlusions in CPRs due to inaccurate centerline definition. Most of these artifacts are obvious or easily identified when additional views, complementary viewing modalities, or source images are reviewed.

Imaging the lower extremity vasculature demands anatomic coverage of well over 100 cm. As the typical maximum FOV in current commercially available MR scanners is on the order of 40 to 45 cm, the peripheral vascular tree exceeds this by a factor of two to three times. In conventional intra-arterial imaging where the imaging FOV is even smaller, this problem is solved by using a stepping table approach with multiple injections of contrast material or a bolus-chase approach, whereby the bolus of contrast material is filmed and followed down the lower extremity by rapid table translation between several contiguous locations (48). Contrast-enhanced (CE) peripheral MRA essentially uses the same two strategies to image the peripheral vasculature.

When planning a peripheral MRA study, the relative needs for temporal resolution, spatial resolution, and signal-to-noise ratio (SNR) must be balanced. In general, higher main magnetic field strengths, higher maximum gradient amplitudes, and faster gradient systems allow for better imaging protocols to depict peripheral arterial disease. These system attributes are more important for CE MRA, which is currently considered the state-of-the-art for imaging the peripheral vascular tree, than for nonenhanced MRA.

A minimal main magnetic field strength of 1.0 T is needed for peripheral MRA. Systems with powerful gradients offer the greatest efficiency and flexibility.

The use of surface coils increases the SNR and is most important for imaging the tibial vessels, particularly at 1.0 T and 1.5 T. This SNR boost can be invested in temporal or spatial resolution or in combinations of the two. An increase in spatial resolution increases arterial conspicuity and improves disease characterization in small, distal, diseased arteries. An increase in temporal resolution helps to avoid venous enhancement and can display collateral filling patterns to good vantage.

Phased-array surface body- or torso coils can be used to image the lower leg. In addition, dedicated multistation peripheral vascular coils with coverage exceeding 100 cm are widely available (Fig. 21-12). In cases where a protocol targets a single foot, a head or knee coil can be effective (Fig. 21-13). Several authors have shown that the use of such coils benefits signal-to-noise and anatomical coverage (49,50,51).

An important technical advance for CE MRA, enabled with the use of localized coils, is parallel imaging (52,53,54). Parallel imaging speeds up data acquisition by replacing the relatively slow spatial encoding through the use of gradients with a faster spatial encoding that uses coil sensitivity profiles. In theory, acquisition duration can be decreased by a factor R equal to the number of coil elements. However, the acceleration is offset by a reduction in the SNR equal to √R.

Several different MRA techniques have been described to image the peripheral vascular tree. These are (a) phase contrast (PC) MRA, (b) time-of-flight (TOF) or inflow MRA, (c) 3D half-Fourier fast spin echo MRA, (d) balanced steady state free precession (bSSFP) MRA and, (e) CE MRA. The latter technique is currently by far the most widely used, although noncontrast techniques are being re-examined to address recent concerns about nephrogenic systemic fibrosis associated with gadolinium administration. A discussion of this reaction can be found in Chapter 22. A summary of the relative merits and shortcomings of MRA techniques can be found in Table 21-8, and detailed descriptions are found in Chapter 2.

In nearly all of the reported studies on peripheral CE MRA, conventional 0.5 M extracellular contrast agents have been used. The intravascular half-life of commercially
approved agents is about 90 seconds (110). Enough contrast must be injected to decrease the T1 of blood to values smaller than those of stationary background tissues. To selectively depict the vasculature, this means that the T1 of blood must be reduced to a value well below that of fat (T1 at 1.5 T = 270 ms).

Typically, between 0.1 and 0.3 mmol/kg of contrast agents is injected (i.e., between 15 and 45 mL for a 75-kg patient), followed by 15 to 30 mL saline injection to flush contrast from injection tubing and veins into the central venous and arterial circulations.

When a TR 2D test-bolus approach is used to image the lower legs and pedal arteries first, usually around 5 to 7 mL of contrast is used, followed by a slightly larger saline flush volume, to make sure that the contrast medium is flushed from tubing and veins into the central circulation. When a hybrid approach is used, the lower legs are usually imaged with 15 to 20 mL of contrast medium and the aortoiliac and upper leg arteries with 20 to 25 mL.

An empirical strategy that works well in clinical practice is to prescribe the contrast injection duration to last for about 40% to 60% of the acquisition duration.

The amount of contrast to be injected as well as injection speed and amount of saline flush depend on variables such as the scan duration and technique used (i.e., single vs. multiple injection). Various single and multiple-phase injection rates and different saline flush volumes have been used successfully.

In general, either a fixed rate of about 1.0 mL/s is used or dual-phase injections with higher initial injection rates of up to 2.0 mL/second for 10 to 20 mL of the contrast medium with a lower rate for the remaining contrast (as low as 0.5 mL/second) (51,111). On older and slower systems, the injection rate is usually kept to well below 1.0 mL/second (73,74).

In a recently published study, Boos and associates (80) found that increasing the amount of contrast injected as well as saline flush volume increases bolus length and improves small vessel conspicuity but does not necessarily result in higher vessel-to-background contrast (80). Conversely, injecting a fixed amount of contrast agent faster leads to a more compact and shorter bolus duration. In another study, Czum et al. (112) demonstrated that by using a dual-phase injection in which the first part of the contrast bolus is injected slowly (0.7 mL/second) and the second part of the injection is faster also improves vessel conspicuity. Sample injection protocols for standard three-sequential-station imaging, a hybrid protocol, and a 2D test bolus protocol are listed in Table 21-9. More details about MR contrast media and administration can be found in Chapter 5.