9. Advanced Peripheral Artery Vessel Wall Imaging and Future Directions

Adrián I. Löffler¹ and Christopher M. Kramer²

(1)

Division of Cardiovascular Medicine, University of Virginia Health System, Charlottesville, VA, USA

(2)

Division of Cardiovascular Medicine and Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, VA, USA

Adrián I. Löffler

Email: al2ys@virginia.edu

Christopher M. Kramer (Corresponding author)

Email: ckramer@virginia.edu

Keywords

Peripheral arterial diseasePlaque imagingUltrasoundComputed tomography angiographyMagnetic resonance imaging

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 [1]. 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 [2]. A recent histopathologic study has suggested that atherothromboembolic disease is a primary feature of PAD [3]. 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)

IVUS is 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 [4]. 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) [5]. 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 [6]. 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 [10]. 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 [10]. Another limitation is its invasiveness and higher costs as it requires an invasive peripheral angiogram.

../images/466148_1_En_9_Chapter/466148_1_En_9_Fig1_HTML.jpg — Fig. 9.1

Atheroma morphology by IVUS. Soft (left), mixed fibrous and calcified (center), and heavily calcified atheromas (right) are illustrated. (From Nissen and Yock [5]; with permission from Wolters Kluwer Health, Inc.)

Computed Tomography Angiography (CTA) and FDG-Positron Emission Tomography/CT (FDG-PET/CT)

CTA has 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% [11]. The presence of dense focal calcifications in the arterial wall can lead to overestimation of the degree of stenosis [12]. 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 [13]. 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 [2]. 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) [2]. 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.

../images/466148_1_En_9_Chapter/466148_1_En_9_Fig2_HTML.jpg — Fig. 9.2

Lower limb ¹⁸F-NaF imaging: non-contrast CT (*top left*) with a rim of calcification of the vessel, ¹⁸F-NaF PET (*top right*), and fused ¹⁸F-NaF PET/CT (*bottom left*) of the superficial femoral artery (*arrow*) at the level of the adductor canal, demonstrating significant vessel uptake in this symptomatic patient. In addition, there is prominent uptake seen in the vessel at the same level on the coronal image (*bottom right*). (Reprinted from Evans et al. [2], page 7; http://creativecommons.org/licenses/by/4.0/; no changes were made)

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 [2]. 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 [14]. This demonstrated excellent reproducibility of ¹⁸F-FDG uptake as 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 [15].

../images/466148_1_En_9_Chapter/466148_1_En_9_Fig3_HTML.jpg — Fig. 9.3

(Reprinted from Silvera et al. [15]; with permission from Elsevier) (a) Transverse MR and FDG-PET/CT images demonstrating a collagen rich plaque of the right common carotid artery. The T2-weighted (T2W) image demonstrates the right common carotid artery (white arrow), the jugular vein (“v”), the sterno-cleido-mastoid muscle (‡) and the thyroid cartilage (†). Carotid artery wall appears hyperintense on T2W (white arrow) and on proton density weighted (PDW) images. CT confirms the absence of calcification in the artery wall. The right common carotid artery is displayed on the computed tomography (CT) and on the fused positron emission tomography/CT (PET/CT) images (white dashed circle). (b) Transverse MR images and corresponding FDG-PET/CT images indicate a carotid artery lipid-rich necrotic core plaque, hypointense on T2W (white arrow) and on PDW images. CT image demonstrates the absence of calcification. The white dashed circle demonstrates FDG uptake into the entire artery section on the PET/CT image

Magnetic Resonance Imaging (MRI)

Contrast-Enhanced Techniques

Contrast-enhanced magnetic resonance 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 [16]. 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 [10]. 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 [10]. 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 gadolinium from undergoing this technique.