In the field of peripheral arterial disease (PAD), the ankle-brachial index (ABI) is considered the gold standard imaging modality for initial screening or diagnosis of lower extremity PAD based on current clinical practice guidelines . While the ABI is an excellent study for diagnosing peripheral arterial occlusion, it has limited utility for assessing arterial wall disease. Being able to directly measure plaque and peripheral arterial remodeling in arterial walls may be better suited for defining disease burden. It is widely recognized that PAD is more complicated than a flow-limiting process and that atheromatous plaque is a nidus for inflammation with consequent risk of plaque rupture . A recent histopathologic study has suggested that atherothromboembolic disease is a primary feature of PAD . We will review the current imaging techniques presently used for vessel wall imaging including intravascular ultrasound (IVUS), fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), and magnetic resonance imaging (MRI).
Intravascular Ultrasound (IVUS)
IVUSis an imaging technique that uses a transducer or probe attached to a catheter that generates real-time ultrasound waves and provides a 360-degree cross-sectional view of arteries . Whereas angiography portrays only a 2D profile of the lumen, ultrasound allows for real-time cross-sectional image acquisition of vessel wall atheromatous plaques, intimal thickening, media and adventitia (Fig. 9.1) . IVUS can also be used to define plaque morphology (i.e., soft, fibrous, calcified, or mixed) and identify presence or absence of a lipid core in the plaque . IVUS has been studied for measuring regression or regression of atherosclerosis and restenosis after percutaneous interventions [4, 7–9]. IVUS historically was the gold standard for quantitative and qualitative evaluation of the vascular wall and lumen . However, IVUS is not suitable in the peripheral vasculature as approximately 50% of vessel segments aren’t quantifiable due to extensive vessel wall calcifications resulting in dorsal echo extinction . Another limitation is its invasiveness and higher costsas it requires an invasive peripheral angiogram.
Computed Tomography Angiography (CTA) and FDG-Positron Emission Tomography/CT (FDG-PET/CT)
CTAhas the advantage of higher spatial resolution compared to ultrasound. Since the arrival of multidetector scanners and multiple cross-sectional imaging allowing for rapid acquisition times, the use of CTA has grown. CTA also allows for three-dimensional (3D) imaging of the peripheral arterial tree which can be useful when planning revascularization strategies. CTA has shown to be effective in identifying >50% stenotic lesions in PAD with a sensitivity of 95% and specificity of 96% . The presence of dense focal calcifications in the arterial wall can lead to overestimation of the degree of stenosis . Other limitations of CTA include the need for iodinated contrast and ionizing radiation exposure.
FDG-PET/CT can be used to evaluate atherosclerotic plaque composition in the superficial femoral artery . PET utilizes positron-emitting radiotracers that encounter electrons in neighboring tissues that lead to annihilation reactions resulting in emission of gamma photons which are detected by scintillation detectors on the scanner. The regions of tracer uptake detected by PET need to be co-registered with CT (PET/CT) or MRI (PET/MRI) to link the region of uptake with an anatomical location. The advantage of PET is that it can directly measure the metabolic processes within plaque . Different radiotracers can be used to target and measure the distinct metabolic features of atherogenesis such as macrophage-mediated inflammatory change (18F-fluorodeoxyglucose), hypoxia (18F-fluoromisonidazole), and microcalcification (18F-sodium fluoride) . Figure 9.2 shows a highly calcified superficial femoral artery (SFA) on CT with the uptake of 18F-sodium fluoride (18F-NaF) on PET in the calcified plaque region of the vessel.
18F-fluorodeoxyglucose (FDG) is the mainstay radioligand in PET imaging and thus has been the most commonly used radiotracer in atherosclerosis. FDG is an analogue of glucose which accumulates intracellularly via glucose transporter member (GLUT) 1 and 3 in proportion to demand for glucose. GLUT 1 and 3 are upregulated during atherogenesis due to hypoxia within the plaque core . A small study of 20 patients underwent PET/CT of the iliac, femoral, and carotid arteries 90 minutes after 18F-FDG administration with repeat imaging 2 weeks later . This demonstrated excellent reproducibility of 18F-FDG uptakeas a marker of inflammation within vessel wall plaque. This technique along with complementary MRI has been used to classify plaque into three different groups, collagen, lipid-rich necrotic core, and calcium, as shown in Fig. 9.3 .
Magnetic Resonance Imaging (MRI)
Contrast-enhanced magneticresonance angiography and CT angiography are both useful for diagnosing and assessing PAD; however, they don’t provide information on arterial remodeling and can underestimate the extent of atherosclerosis . Furthermore, contrast agents limit the use of both of these modalities in certain patients, including those with advanced chronic kidney disease. Below we will summarize different MRI techniques that have been developed for arterial wall assessment.
MRI has the advantage of lack of radiation exposure and thus can be used for serial arterial wall assessments. Technical advances have enabled improved spatial resolution which permits imaging of structures smaller than 1 mm in diameter with MRI . This paved the path for new studies using MRI for noninvasive assessment of atherosclerotic plaque in vivo [17, 18]. Meissner et al. studied high-resolution MRI in the femoral arterial segments of patients with PAD and compared it to IVUS . MRI was performed at 1.5 T with a three-dimensional (3D) time-of-flight sequence with in-plane resolution of 0.78 × 0.49 mm2. When compared with IVUS,they demonstrated precise assessment of cross-sectional lumen area and extent of calcification in PAD. Figure 9.4 demonstrates how hypointense plaque can be clearly differentiated from the hyperintense lumen. This technique however does require gadolinium contrast for 3D contrast-enhanced angiography to allow for exact position of the MR imaging slices. This would preclude patients with stage 4 or 5 chronic kidney disease or allergic reactions to gadoliniumfrom undergoing this technique.