Non-invasive imaging techniques in lower extremity artery disease

Background

A variety of imaging tests are available for lower extremity artery disease (LEAD). Duplex ultrasound (DUS), computed tomography angiography (CTA) and magnetic resonance angiography (MRA) can all provide useful information non-invasively. But what is the place of imaging tests in this scenario?

The ankle-brachial index (ABI) is the first diagnostic step after clinical examination. An ABI <0.90 has 75% sensitivity and 86% specificity to diagnose LEAD [1,2]. Sometimes when clinically suspected, a normal ABI does not definitely rule out a diagnosis of LEAD; further post-exercise ABI and/or imaging tests are necessary. In addition, imaging tests can be useful in patients with a high ABI (>1.40) associated with medial calcification [2,3].

The objectives of imaging techniques in LEAD are as follows:

1) identifying sites of stenosis,

2) defining the degree of arterial obstruction,

3) characterising the morphology, exact location and extent of the disease,

4) evaluating distal run-off and collateral circulation.

Fundamentally, this information is useful for patients with symptomatic LEAD. Imaging helps to localise the lesions targeted for revascularisation (which may require invasive haemodynamic confirmation), the selection of appropriate equipment or adjunctive devices, and the choice of arterial access site (i.e., antegrade versus retrograde common femoral access, retrograde pedal access, etc.). These considerations will determine the patient position on the table as well as room preparation, and can help to minimise procedure duration, contrast use, and radiation exposure [4,5].

After revascularisation, either endovascular or surgical, imaging techniques provide information on the permeability of the ducts and the presence of complications.

The choice of the examination should be determined using an individualised approach to the anatomic assessment for each patient, including risk-benefit assessment of each study type.

Imaging tests for lead diagnosis

LEAD imaging tests can provide anatomical information on the arterial stenosis together with their haemodynamic repercussions, depending on the modality chosen. In general, techniques must be combined in order to achieve a proper evaluation of each patient.

Duplex ultrasound 

Duplex ultrasound (DUS) is usually the first-line imaging modality for screening. It assesses peripheral artery stenosis. DUS provides extensive information on arterial anatomy and haemodynamics, and includes B-mode echography and Doppler modalities. The lesions are located by two-dimensional (2D) ultrasonography and colour Doppler mapping, while the degree of stenosis is estimated mostly by Doppler waveform, peak systolic velocities and velocity ratio analysis [2].

The most commonly used criteria for identifying arterial stenosis >50% are peak systolic velocity (PSV) >200 cm/s, PSV ratio >2.0, and aliasing and spectral broadening seen with colour Doppler [6]. High-grade stenosis (PSV >300 cm/s, PSV ratio across the stenosis >3.5 and/or monophasic post-stenosis flow) is common in the case of >70% proximal arterial obstruction [2,7].

Advantages: DUS provides anatomic and haemodynamic information non-invasively, it has great availability, renal function does not affect the safety of the test, it is the least costly imaging technique and it can be performed by the patient’s bed. No side effects or adverse events have been reported. Excellent tolerance and lack of radiation exposure make DUS the method of choice for routine follow-up [8].

Pitfalls: Due to severe artery calcification, it is sometimes challenging to differentiate high-grade stenosis from complete occlusion. In addition, extensive calcification may result in incomplete examinations.

DUS presents limited accuracy for iliac disease due to body habitus and bowel gas. A normal DUS at rest should be completed by another imaging test when iliac stenosis is suspected [7,8].

The major limitation of DUS compared with other imaging techniques is that it does not provide full arterial imaging as a clear roadmap, as do the other techniques [2].

Finally, the technique is operator-dependent and proper training is mandatory. Therefore, complete DUS scanning of the entire arterial network can be time-consuming.

Accuracy: DUS is an accurate technique for LEAD; it presents a sensitivity of 85-90% and a specificity of >95% to detect stenosis >50%. No significant differences were found between the above-the-knee and below-the-knee lesions [9].

More recent techniques, such as flow imaging or live three-dimensional (3D) echography, as well as intravascular ultrasound for plaque characterisation, require further investigation; their use is still limited in LEAD [2].

When surgical revascularisation is planned, DUS is also important to address vein quality for bypass substitutes. It is also the method of choice for routine follow-up after revascularisation, especially to assess the surveillance of venous grafts [2,7].

In all cases, the information provided by DUS should be combined with ABI measurement, and multiple criteria should be used for reliable estimation of stenosis.

Computed tomography angiography

Computed tomography angiography (CTA) is an anatomic imaging test. Similar to digital subtraction angiography (DSA), CTA displays a “roadmap” of the vascularisation (lesion localisation and severity, together with upstream/downstream status), which is essential for determining interventional strategies [2,10].

This technique provides information regarding the characterisation of stenosis, such as localisation, number and length of occlusive lesions, degree of calcification and arrangement of the calcium component, quality of distal run-off, and also about extravascular findings.

Adequate peripheral CTA can be performed with a 16-detector row CT scanner. However, currently most of the equipment uses 64, 128 or 256 detector rows. The coverage of peripheral CTA includes the abdominal aorta from the celiac trunk to the foot. These types of study always require the use of intravenous iodine contrast for adequate assessment of the arterial lumen.

One of the important technical points of the study is to inject an appropriate iodine concentration inside the vessel lumen to depict small vessels (1-2 mm) and differentiate vessel lumen from wall calcification. The bolus arrival is automatically detected at the level of the proximal abdominal aorta and the image acquisition is triggered with a delay varying between 6 and 10 seconds to ensure that the distal arteries will be properly opacified. A delayed acquisition covering knee, leg and foot is a good alternative when distal opacification is likely to be suboptimal on the first pass [10].

The interpretation of CTA is based on the axial images and the use of advanced post-processing techniques. While volume-rendered 3D reconstruction of the arterial tree provides a global overview for rapid identification of pathology, maximum intensity projection (MIP) images provide similar views to traditional angiography and are useful for qualitative assessment of the degree of stenosis. The usefulness of both volume-rendered and MIP images is limited by obscuration of the vessels by bones. Thus, automated software techniques for bone removal have been implemented, although they still require some degree of manual correction. Either automated or interpreter-generated centrelines in the vessel of interest can be placed to obtain curved planar reformations, providing both longitudinal and cross-sectional views of the vessel, which are useful for quantitative measurements [7,11].

Advantages: Rapid non-invasive acquisition (<5 minutes), higher spatial resolution that allows good evaluation of calcifications, stents, bypasses and concomitant aneurysms; it enables scanning of the entire vascular tree in a limited period and 3D reformatting. The capacity of CTA to visualise the arterial wall, as well as the lumen, gives the interpreter a greater degree of certainty when arriving at less common diagnoses [12].

Pitfalls: This method does not provide haemodynamic data for each lesion, has a high radiation dose and uses iodinated contrast agents. However, while nephrotoxicity can be limited by minimising contrast agent volume and ensuring adequate hydration before and after imaging, the benefit of acetyl-cysteine to limit nephrotoxicity is uncertain [2,13]. In addition, severe calcification may overestimate stenosis severity, mostly in distal arteries. Furthermore, the possibility of allergic reactions, the higher costs and the limited availability of this imaging test should be taken into account.

Accuracy: The reported sensitivity and specificity of CTA to detect aorto-iliac stenosis >50% were 96% and 98%, respectively, with similar sensitivity (97%) and specificity (94%) for the femoropopliteal region [2,14,15].

Magnetic resonance angiography 

Magnetic resonance angiography (MRA) provides functional and morphological information that is useful to distinguish anterograde from retrograde perfusion and to estimate stenosis severity. As with CTA, MRA examinations are indicated when a revascularisation therapy is planned or when DUS results are inconclusive.

There are three MRA sequences for peripheral artery imaging: 1) flow-dependent techniques without contrast agent based on proton inflow (time-of-flight), 2) phase shift of the flowing protons (phase contrast angiography), and 3) contrast-enhanced (gadolinium) MRA [10].

The non-contrast techniques (phase contrast and time-of-flight sequences) have inferior resolution and are susceptible to motion artefacts and stenosis overestimation. For these reasons, the contrast-enhanced MRA acquisition sequence is currently preferred.

Advantages: MRA is extremely useful in patients with mild to moderate chronic kidney disease (CKD). Compared with CTA, MRA does not need iodine contrast and has higher soft tissue resolution.

Pitfalls: Motion artefacts are more frequent, partly because acquisitions of MRA sequences are more time-consuming and it is necessary that the patient maintain the same position during the acquisition of the study. A relative disadvantage includes a tendency to overestimate stenosis because of flow turbulence, and metal clips can cause artefacts that mimic vessel occlusions [7]. Contraindications include claustrophobia, pacemakers and implantable cardioverter defibrillators (except magnetic resonance imaging compatible devices). Gadolinium contrast agents cannot be used in the case of severe renal failure (GFR <30 mL/min/1.73 m²). In the latter case, the risk of nephrogenic systemic fibrosis following gadolinium administration should not be underestimated [2,16].

Of note, MRA cannot visualise arterial calcifications, which may be a limitation for the selection of the anastomotic site for a surgical bypass.

Additionally, poor visualisation of steel stents, the higher cost of the method and its limited availability are also limiting factors to consider [2].

Accuracy: The sensitivity and specificity of MRA are ~95% for diagnosing segmental stenosis and occlusion [17,18].

Digital subtraction angiography  

Not long ago, digital subtraction angiography (DSA) was considered the standard reference in vascular imaging. Given its invasive character and risk of complications, it has mostly been replaced by other less invasive imaging methods [2].

DSA is rarely required for diagnostic purposes and is used only in highly specific situations with discordant non-invasive imaging results.

Currently, its main use is in combination with endovascular therapy. It is also often needed to evaluate below-the-knee arteries in patients with chronic limb-threatening ischaemia, given the limitation of other imaging tools to detect ankle/pedal segments suitable for distal bypass [2].

In certain clinical settings, non-invasive imaging studies for anatomic assessment (i.e., DUS, CTA or MRA) may not be available due to lack of local resources or expertise, hence DSA is the only option. In addition, there are clinical scenarios in which imaging tests may be perceived as conferring greater risk to the patient than invasive angiography (e.g., a patient with advanced chronic kidney disease for whom contrast dose for invasive angiography would be lower than that required for CTA) [8].

Other imaging techniques: positron emission tomography

Positron emission tomography (PET) is useful for the diagnosis of arteritis (Takayasu disease, giant cell arteritis) but not for assessment of atherosclerotic lesions in clinical practice [2].

Test – selection process

The particular modality of choice depends on many factors, including patient demographics and comorbidities, availability and modernity of respective imaging equipment, level of training and confidence of the operating technologists, and local interest and expertise of the vascular team. Each of these factors must be considered when choosing the best imaging examination for an individual patient [19].

In general, DUS is the first imaging test chosen once LEAD has been diagnosed by performing an ABI evaluation.

Next, fundamentally when it is necessary to know the entire vascular tree or in case of aorto-iliac involvement, CTA is the method of choice. Likewise, MRA presents similar diagnostic accuracy. In two studies with patients presenting intermittent claudication, it has been shown that CTA provides the same information as MRA at a lower cost [10,20].

Finally, invasive angiography is indicated when there are controversial results between the different imaging methods or when an endovascular revascularisation strategy is planned.

The accuracy of these imaging modalities is summarised in Table 1 [20] and their main characteristics are shown in Table 2 [7].

Angiography, either non-invasive or invasive, should not be performed for the anatomic assessment of patients with LEAD who do not evidence leg symptoms, since delineation of anatomy will not change treatment for this population [8].

Table 1.  Comparison between different imaging techniques for arterial stenosis >50% in LEAD [9,14,17].

Table 2. Comparison of different imaging tests for patients with LEAD [7].

CTA: computed tomography angiography; DSA: digital subtraction angiography; DUS: duplex ultrasound; MRA: magnetic resonance angiography; +: low; ++:  intermediate; +++: high.

Special situations: acute limb ischaemia

When assessing acute limb ischaemia, the initial imaging test is chosen case by case, based on the patient’s characteristics (renal function, allergy to iodinated contrasts) and the availability of resources in each centre.

The imaging method depends on its immediate availability, making DUS and DSA the most frequently used techniques in these situations [2,8].

In case of associated neurological deficit, urgent revascularisation is mandatory and imaging should not delay the intervention [2,8].

Conclusions

In individuals with clinically suspected LEAD, the ankle-brachial index is indicated as a first-line test for diagnosis. In order to confirm and characterise the disease, DUS is usually the preferred imaging test. When a revascularisation strategy is being planned, accurate details of lesion distribution and distal run-off are necessary to plan interventions. Magnetic resonance and computed tomography angiography replace invasive catheter angiography for the mapping of peripheral occlusive arterial disease.

Finally, data from an anatomical imaging test should always be analysed in conjunction with symptoms and haemodynamic tests prior to any treatment decision.