The Evaluation of Peripheral Arterial Disease with Intravascular Ultrasound

Abstract

Intravascular ultrasound (IVUS) has emerged as a dynamic imaging modality that provides real-time visualization for catheter-based interventions. The image presentation of IVUS permits detailed assessment of plaque and vessel morphology and their response to intervention. IVUS also provides accurate quantitative information regarding lumen area, plaque area, and vessel diameters. In addition, in vivo assessment of atherosclerotic plaques and restenosis has changed the understanding of peripheral arterial disease. In the following review, the utility of IVUS in the treatment of peripheral arterial disease will be reinforced.

VASCULAR DISEASE MANAGEMENT 2011;8(4):E81–E86

Introduction

Digital angiography has paved the road for technical advances in endovascular therapy, and most vascular specialists still consider angiography to be the “gold standard” for defining peripheral arterial anatomay.^1,2Despite providing an accurate roadmap and planar representation of the vessel lumen, angiography provides very little information about the vessel wall or plaque lining the vessel. Furthermore, angiography provides only limited information on the interaction of endovascular devices with the arterial wall. While angiography is necessary for vessel navigation and treating specific anatomic regions, intravascular ultrasound (IVUS) compliments angiography by yielding cross-sectional imaging with improved resolution.

IVUS provides detailed in vivo information regarding plaque shape, plaque composition and overall plaque burden, which have all been evaluated with pathologic confirmation. Foremost, IVUS is an adjunct for determining the adequacy of endovascular interventions, and when treating endovascular failures, IVUS is an invaluable resource for interrogating the potential etiology of failure. Following the advances in endovascular tools, IVUS has provided a wealth of in vivo information that has furthered the development of medical therapy, debulking devices, angioplasty balloons and stents. The following review will illustrate the utility of IVUS for the treatment of peripheral arterial disease (PAD).

Device and Software Considerations

Two manufacturers currently support IVUS catheter systems for use in the peripheral arterial bed (Table 1). Both companies (Volcano Corporation, Rancho Cordova, California, and Boston Scientific Corporation, Natick, Massachusetts) offer low-frequency catheters that are utilized for aortic and venous imaging, but their higher-frequency catheters offer detailed image resolution needed for smaller vessels.

Both companies offer catheters that can be delivered through 5 Fr or 6 Fr sheaths, typically required for iliac artery and infrainguinal arterial interventions. The Boston Scientific catheters have a clear-coated catheter that houses the IVUS catheter and has a wire channel that runs next to the IVUS catheter. The operator must be aware of the potential wire artifact that occurs with this system and be able to recognize its occurrence. In addition, the clear-coated catheter creates a space between the imaging catheter and blood, which is prone to trapping air. Therefore, it is imperative to continually flush the catheter to eliminate air artifact in the system. On the other hand, Volcano catheters are deployed over-the-wire, which eliminates artifact secondary to the wire. The 0.018-inch catheter is a classic over-the-wire system, whereas the 0.014-inch catheter is a rapid-exchange catheter.

There are two different IVUS design strategies: solid-state versus mechanical-state catheters that account for the differences between the two manufacturers. The solid-state catheters rely on miniaturized phased-array elements oriented circumferentially at the tip of the catheter. The elements receive backscattered ultrasound and the signals are routed to a computer terminal, which constructs real-time images. The advantages of a multi-element catheter include: no movable parts (does not require rotation to acquire images of the vessel) and an over-the-wire configuration. The Volcano catheters are based on a solid-state design. The mechanical-state design holds a single rotating element at the tip of the catheter, which captures signals with each revolution. Utilizing this design requires a flexible cable that maintains constant rotation of the transducer element, and it requires flushing the system to eliminate any microbubbles that can be the source of air artifact. Boston Scientific catheters rely on the mechanical-state design.

Both catheter systems provide excellent image resolution, and both catheters obtain the best images when the transducer is perpendicular to the vessel wall. Typically, images are obtained when performing a manual pull-back, as the catheter is more likely to center in the lumen. Another issue regarding image quality unique to mechanical-state IVUS is non-uniform rotational distortion (NURD); this occurs in tortuous vessels, which places stress on the catheter creating non-uniform rotation. Boston Scientific has combated this distortion with an automatic software correction that helps eliminate NURD.

Both IVUS systems require a computer console with a representative software package. Typical measurements obtained with IVUS include: lumenal diameters, lumenal cross-sectional area, vessel wall diameters, vessel wall area, plaque shape, plaque length, and plaque volume. In addition, the operator can determine the presence of thrombus, intimal disruption, dissection, and ulceration. The Volcano system also offers color flow with both the 0.018-inch and the 0.014-inch catheters. Unlike transcutaneous duplex ultrasound, color flow does not detect velocity shifts; the software relies on changes in a single image from one frame to the next frame (typically 30 frames/second are measured). The change detected in repetitive frames is represented in red, and in areas of stenosis the color changes to orange. In addition, Volcano offers virtual histology software that characterizes plaque morphology. The software relies on IVUS images created by the intensity and frequency of returning signals that vary depending on the type of tissue surrounding the catheter. The representative images have been validated in pathologic specimens of coronary arteries in order to delineate plaque characteristics into four categories: fibrous, fibro-fatty, necrotic-lipid and calcific. The software assigns a color to each profile and labels the plaque chosen for interrogation.³

Vascular Pathology

Plaque shape. The degree of plaque asymmetry within the vessel is one of the most underappreciated factors in the context of treating vascular disease with interventional devices. The shape of the plaque cannot be fully appreciated, even with bi-planarangiography of the diseased segment. Atherosclerotic plaques develop largely in areas of low wall shear stress, which is most commonly encountered at flow dividers with areas of flow separation. Most peripheral arteries are curved arterial segments that lend themselves to flow separation throughout the length of the vessel such that the internal curvature of the vessel is subjected to less wall shear stress than the outer curvature. A primary example is the superficial femoral artery as it traverses from the thigh to the popliteal fossa. Figure 1A illustrates an example of an eccentric plaque in the superficial femoral artery. Based on angiography alone, this would be interpreted as stenosis, but without the axial images, the operator is unable to fully appreciate the anatomy of the stenosis. In addition, Figure 1B illustrates an example of concentric plaque within the superficial femoral artery.

Plaque morphology. One of the main advantages of IVUS is the ability to objectively assess plaque morphology. Understanding the morphology of the plaque being treated has several implications for the treatment of peripheral vascular disease. Qualitative assessment of echogenicity alone can be inaccurate due to the similarities of echogenicity between different tissue compositions: thrombus, lipids, fibrous material and calcium. Analyzing the raw radiofrequency data obtained from IVUS allows the development of radiofrequency spectral profiles for different tissue types. This process, “virtual histology,” allows the objective classification of plaque morphology into categories: fibrous, fibro-fatty, necrotic-lipid and calcific.

Virtual histology has most commonly been applied to the coronary vascular bed,^4,5 and the algorithm has been validated for carotid arteries.⁶ Kashyap et al have contributed a large body of work in the evaluation of peripheral arterial disease, and his group has used a modified algorithm to study peripheral arteries.^7–9 When compared to angiographic assessment, surgeons overestimated the extent of plaque calcification in femoral-popliteal segments, whereas IVUS classified the majority as fibrous plaques based on their radiofrequency profile. In a post-mortem amputation study, Bishop et al identified increasing calcification with increasing distance from the popliteal artery, irrespective of known clinical risk factors (diabetes, hyperlipidemia and chronic kidney disease).⁹

Plaque burden. The disassociation of angiographic findings and histologic analysis has been documented in both the coronary and peripheral vascular territories. Necropsy studies in patients who had previously undergone coronary angiography determined that 33% of patients were found to have coronary atherosclerosis unidentified by angiography.¹⁰ In the peripheral vascular bed, Bishop et al studied a select group of patients who had undergone angiography prior to amputation. The angiograms were compared to perfusion fixed arterial histology obtained from amputation specimens.⁴ Angiography underestimated stenosis severity and arterial diameter and was discordant from actual plaque architecture.^8,9

Comparing the maximal diameter stenosis from angiography to the maximal area stenosis from IVUS, angiography consistently underestimates the degree of stenosis by 10%. This difference in interpretation may account for some of the false-negative studies (33–39%) identified in post-mortem histological studies compared to angiography.^8,10

Qualitative variables assessed by angiography are replaced with an objective IVUS measurement. For instance, when determining the overall length of plaque stenosis, angiography underestimates the length of stenosis as much as 5 mm. Similarly, plaque concentricity is severely underestimated by angiography.⁷The high level of resolution of IVUS provides information that cannot be compared to angiography or any other surface imaging modality.

Clinical Applications for Peripheral Arterial Disease

Angioplasty and stenting. The treatment of peripheral arterial disease (PAD) is now as heterogenous as the disease process. Treatment options include medical therapy, exercise therapy, angioplasty, atherectomy, stents, stent grafts and eventually drug-coated balloons and drug-eluting stents. Limitations of angiographic evaluation may account for the widely disparate results of treatment for PAD. In the treatment of femoral-popliteal disease, trials comparing medical therapy versus angioplasty for the treatment of claudication have failed to demonstrate a difference in symptom relief or walking distance over 2–6 years of follow-up.^11–13 This may reflect either recurrent disease or remnant occlusive disease that was not completely treated initially. The BASIL trial compared surgical bypass to percutaneous transluminal angioplasty in the treatment of chronic limb ischemia due to infra-inguinal disease. No demonstrable differences were identified in patency or amputation-free survival.¹⁴ However, 20% of patients in the angioplasty arm were technical failures and a high fraction of angioplasty patients required secondary procedures. Lastly, the addition of self-expanding stents and stent grafts has improved the immediate angiographic result, but has failed to demonstrate an improvement in long-term patency, ambulatory status, and amputation free survival.^15–17 No matter which modality is utilized (angioplasty, atherectomy, stenting, or covered stenting); the primary patency rate is relatively fixed at approximately 50–80% over 2 years. IVUS may provide the information needed to improve upon femoral-popliteal artery interventional outcomes, which currently suffer from limited durability.^14,17

IVUS has demonstrated superior technical outcomes in the coronary literature, and in combination with drug-eluting stent technology, the subacute stent thrombosis rate has been reduced from 20% to negligible rates.¹⁸ Several studies documented an unexpectedly high (approximately 80%) percentage of stents that were incompletely expanded, incompletely apposed or asymmetrically expanded.^19,20 These in vivo observations lead to high-pressure balloon angioplasty in order to correct these measures in the coronary bed. Likewise, IVUS could potentially translate to improved technical outcomes in peripheral arterial beds. Experience in the peripheral arteries highlights the difficulties of determining the beginning and end of disease with angiography, which may lead to inadequate treatment of the occlusive process. Sizing of endovascular devices, balloons and stents is based upon luminal rather than true vessel diameters. Thus, patients may return for treatment of remnant rather than recurrent disease.

Buckley and colleagues have demonstrated that utilizing IVUS as an adjunct to iliac angioplasty and stenting improves iliac artery patency rates.^21,22 In the group that was treated with both angiographic and IVUS assessment, 20 of 49 patients (41%) were found to have underdeployed stents by IVUS even though they appeared to be adequately apposed based on angiography. This group (angiography + IVUS) experienced a 100% primary patency rate at 3 years, whereas the group of patients treated based on angiography alone experienced an 82% primary patency rate.²¹ There were 4 early failures in the angiography-alone group, and all 4 patients were documented to have underdeployed stents on IVUS at the time of re-intervention. They concluded that IVUS helped define arterial diameter and adequacy of stent deployment leading to improved patency and obviating the need for secondary procedures.²¹

The ability to assess stent expansion and stent apposition is extremely challenging when utilizing angiography alone. Figure 2 illustrates a case of failed stent expansion that was recognized at the time of the procedure and treated with a balloon-expandable stent. Figure 3 illustrates a case of failed stent apposition that was not recognized in the initial procedure. This error partly contributed to acute stent thrombosis requiring thrombolysis and repeat angioplasty and stenting. After reviewing these 2 cases, it is clear that IVUS provides the surgeon with additional information above and beyond that of angiography, which should translate to better results.

Restenosis. IVUS has provided an in vivo tool for evaluating the mechanisms of restenosis. The primary mode of restenosis has uniformly been attributed to aggressive neointimal hyperplasia, which proliferates from an endothelial-derived process. Utilizing IVUS for follow-up evaluation of restenosis, the exact etiology of restenosis can be determined in individual patients. IVUS studies have identified another primary process contributing to restenosis: contraction of the treated vessel or negative remodeling. Several studies have documented the loss of vessel size or contraction of the vessel following intervention.^23,24 In coronary artery restenosis patients, loss of lumen cross-sectional area correlated strongly with loss of external elastic lamina area and was only weakly associated with increased plaque/media volume. In addition, patients who experienced an increase in external elastic lamina area were less likely to develop restenosis and experienced a positive adaptive response to intervention.²³Therefore, there are two mechanisms accounting for late luminal loss following endovascular interventions: an aggressive neointimal response and negative remodeling of the treated segment.

Future Developments

Combined therapeutic devices have been primarily directed at treating chronic total occlusions. The most common reason for technical failure is the inability to re-enter the true lumen beyond the occlusion. The Pioneer Catheter (Medtronic Vascular, Santa Rosa, California) integrates IVUS in a dual-lumen 6 Fr catheter in order to direct the wire back under direct vision into the true lumen of the vessel. Other logical strategies would incorporate atherectomy devices with IVUS so that recanalization could be directly visualized. In addition, this would allow debulking eccentric plaques without disrupting normal intima on the opposing vessel wall. There are combined IVUS/atherectomy devices being tested for the coronary arteries. In addition, incorporating IVUS into a wire would allow continuous imaging with current therapies; this modification has also been under active investigation.²⁵

Currently available IVUS software provides excellent axial images, and provides longitudinal, stacked images of the vessel lumen acquired during a pullback. The quality of the longitudinal reconstructions is variable. Improved software reconstructions will eventually allow three-dimensional reconstruction of IVUS imaging and “on-the-fly” modification for immediate interpretation during treatment. As the software becomes more advanced, it will also conform to image onlays and fusion with other imaging modalities.

Summary

IVUS has played an important role in the examination of in vivo peripheral vascular disease. This technology has provided an examination of plaque distribution, vessel remodeling and response to interventional treatment. In addition, IVUS serves as a technical adjunct for endovascular procedures that has demonstrated superior outcomes compared to angiography alone. In some instances, IVUS may be used as a therapeutic device in order to complete endovascular procedures. Incorporating IVUS into wires or combined devices along with improving upon image acquisition and processing will further extend current applications.

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From the Department of Vascular Surgery, San Antonio Military Medical Center, San Antonio, Texas. The author reports no conflicts of interest regarding the content herein. Address for correspondence: Zachary M. Arthurs, MD, Department of Vascular Surgery, San Antonio Military Medical Center, 24835 Cloudy Creek, San Antonio, TX 78255. E-mail: arthursz@mac.com