Intravascular Ultrasonography Procedures

Intravascular ultrasonography (IVUS) is an invasive imaging procedure that provides intravascular images of the coronary arteries and other blood vessels. Intravascular ultrasonography has played a critical role in enhancing the understanding of coronary atherosclerosis pathophysiology and has facilitated the refinement of diagnostic and therapeutic strategies for various vascular pathologies. Intravascular ultrasonography has become increasingly important in both clinical and research applications,[1] and it has played an integral role in the evolution of interventional cardiology.[2, 3] Intravascular ultrasonography in interventional cardiology is an adjunctive procedure to coronary angiogram; as such, any contraindication to coronary angiography applies to intravascular ultrasonography as well.

In general, risks and discomforts involved in IVUS include those associated with all catheterization procedures. Major complications, including dissection or vessel closure, are rare (<0.5%). The most frequently reported complication is transient coronary spasm (occurring in 1-3% of examinations), which responds to intracoronary glyceryl trinitrate.

(See the image below.)

An expert consensus committee commissioned by the American College of Cardiology, in collaboration with the European Society of Cardiology, has provided a framework for standardization of nomenclature, methods of measurement, and reporting of intravascular ultrasonography results.[4]

Preinterventional intravascular ultrasonography imaging allows the assessment of plaque distribution, ostial involvement, lumen and vessel area and diameters, extent of calcification, and the presence of thrombi or dissections.[5, 6, 7] It can alter strategy and the decision to use a particular device.

Two major trials, the Strategy for Intracoronary Ultrasound-Guided PTCA and Stenting (SIPS) trial and the Balloon Equivalent to Stent (BEST) study evaluated the potential benefit and demerits between ultrasound-guided balloon angioplasty and routine stenting.[8, 9] In the SIPS trial, approximately 50% of patients in each group received a stent at the time of the index procedure. Acute gain was greater in the IVUS-guided group than in the angiography-guided group, but angiographic 6-month follow-up revealed no difference in the primary endpoint of minimum lumen diameter. Although no difference was noted in the secondary endpoint of short-term target lumen revascularization, long-term clinical follow-up showed a significant decrease in clinically driven target lumen revascularization in the ultrasound group compared with the angiography group. In the BEST trial, at 6 months, 20 of 119 patients in the aggressive balloon angioplasty group and 21 of 116 patients in the routine stent implantation group had restenosis, along with no statistical difference in minimal luminal diameter or lumen cross-sectional area, thus fulfilling the prespecified criteria for noninferiority.

Although intravascular ultrasound-guided balloon angioplasty is a noninferior alternative to routine stenting, this approach is certainly more time consuming and requires meticulous attention to detail and expertise in intravascular ultrasonography image acquisition and interpretation. These studies have made apparent that the crossover rate is high, with more than 50% of patients requiring adjunctive stent implantation. In routine clinical practice, stent implantation has gained preference over intravascular ultrasound-guided balloon angioplasty.[10]

The Multicenter Ultrasound Stenting in Coronaries (MUSIC) study established the safety and feasibility of intravascular ultrasound-guided stent implantation.[11] Fitzgerald et al evaluated whether routine ultrasound guidance of stent implantation improved clinical outcome as compared to angiographic guidance alone in the Can Routine Ultrasound Influence Stent Expansion (CRUISE) trial.[12] Although no clinical outcome benefits were demonstrated with routine use of intravascular ultrasonography, a more effective stent expansion was noted when compared with angiographic guidance alone .

Casella et al conducted a meta-analysis of studies done on this topic and demonstrated that intravascular ultrasound-guided stent implantation has a neutral effect on long-term death and nonfatal myocardial infarction compared with an angiographic optimization.[13] However, it was noted that intravascular ultrasound-guided stenting significantly lowers 6-month angiographic restenosis and target vessel revascularizations.

In their appraisal of intravascular ultrasonography and its application in routine angioplasty, Oxford et al have noted that intravascular ultrasonography is better than contrast angiography in key procedural variables, such as measurement of postdeployment stent dimensions, confirming complete stent apposition, and excluding edge dissections that may predispose to both early and late complications, including in-stent restenosis.[14] At present, no guidelines exist on the routine use of intravascular ultrasound-guided angioplasty, but the interventionist should weigh the risks and benefits of this procedure before its application. The clinical usefulness of ultrasound guidance in stent deployment maintains its value. Particularly in small vessels, bifurcation stenting, ostial lesions, long segments, and in left main stenting, ultrasound can provide beneficial guidance.[15, 16]

Intravascular ultrasound plays a vital role in characterization of plaque structures and planning of debulking (atherectomy) procedures by differentiating between superficial (intimal) and deep calcium deposits .[17] Intravascular ultrasonography has emerged as superior to routine angiography at guiding selective plaque removal.[18] Rotational atherectomy is preferred over directional atherectomy in superficial calcification.[19]

Intravascular ultrasonography consists of a miniature ultrasound-mounted catheter that is connected to an electronics console to reconstruct the images transmitted by sound waves. The ultrasound signal is produced by passing an electrical current through the piezoelectric (pressure-electric) crystalline material of the transducer that expands and contracts when electrically excited.

After reflection from tissue, part of the ultrasound energy returns to the transducer. The received signal is converted to electrical energy and sent to an external signal processing system for amplification, filtering, scan conversion, user-controlled modification, and graphic presentation. The ultrasound beam upon reflection remains fairly parallel for a distance (near field) and then begins to diverge (far field). The quality of ultrasound images is greater in the near field because the beam is narrower and more parallel, the resolution is greater, and the characteristic backscatter (reflection of ultrasound energy) from a given tissue is more accurate.Therefore, larger transducers with lower frequencies are used for examination of large vessels because they create a deeper near field.

(See the video below.)

A catheter consists of a miniaturized transducer and a console that reconstructs the image. High ultrasound frequencies are used, typically centered at 20-50 MHz and providing excellent resolution.

Monorail rapid exchange intracoronary ultrasound catheters have an outer diameter ranging between 2.6 and 3.5 Fr (0.87-1.17 mm diameter) and can be advanced through a 6-Fr guide catheter.

Two different types of transducers exist for intravascular ultrasonography: the mechanically rotating transducer and the electronically switched multielement array system.

A single rotating transducer is driven by a flexible drive cable at 1,800 rpm (30 revolutions per second) to sweep a beam almost perpendicular to the catheter. At approximately 1-degree increments, the transducer sends and receives ultrasound signals. They require flushing with saline to provide a fluid pathway for the ultrasound beam, because even small air bubbles can degrade image quality. In most mechanical systems, the transducer spins within a protective sheath while the imaging transducer is moved proximally and distally. This facilitates smooth and uniform mechanical pullback.

Electronic systems use an annular array of small crystals rather than a single rotating transducer. The transducers are activated sequentially to generate the image. The coordinated beam generated by groups of elements is known as a synthetic aperture array. The currently available electronic system provides simultaneous colorization of blood flow.

The imaging console includes components and software necessary to convert the ultrasonography signal to a graphic image on the monitor. Three display modes are currently available. Cross-sectional tomographic views are single-cut cross-sectional images; these are limited by spatial orientation and cannot provide information regarding the length and distribution of plaque. With longitudinal imaging (L mode), computerized image reconstruction techniques present a series of evenly spaced ultrasound images along a single-cut plane to approximate the longitudinal appearance of the artery. Motorized transducer pullback and digital storage of cross-sectional images are necessary for L mode.[20] Three-dimensional (3D) reconstructions of data are also available.[21]

Regarding patient preparation, local anesthesia and minimal general sedation are used, and the patient should lie supine on the angiogram table.

The patient must be anticoagulated, usually with heparin, before inserting the guidewire into the coronary artery. Unless it is contraindicated, image acquisition should be performed after administrating intracoronary nitroglycerin to avoid catheter-induced spasm.

Standard coronary interventional techniques and equipment (guiding catheter and 0.014-inch angioplasty guidewire) are used for catheter delivery for intracoronary ultrasound examination. The catheter is placed distal to the segment of interest. Subsequently, the operator retracts the transducer, either manually or with a motorized pullback device. During pullback, images are obtained and recorded digitally for analysis.

Motorized pullback devices allow withdrawal at a constant speed (between 0.25 mm/s; most frequently 0.5 mm/s), which is essential in serial studies. Motorized pullbacks permit length and volumetric measurements and provide uniform and reproducible image acquisition for multicenter and serial studies. However, inadequate examination of important regions of interest can occur because the transducer does not remain for long at any specific site in the vessel.

A standard intravascular ultrasound image consists of 3 main components: catheter, lumen, and arterial wall. An ultrasound reflection is generated at a tissue interface if an abrupt change in acoustic impedance occurs. In the normal artery, 2 such interfaces are usually observed: one at the border between blood and the leading edge of the intima and a second at the external elastic membrane, which is located at the media-adventitia border. In patients younger than 40 years, the reported normal value for intimal thickness is typically between 0.15 and 0.25 mm.[22] Most investigators use 0.25 to 0.50 mm as the upper limit of normal.

(See the videos below.)

Border identification

Recognizing that all ultrasound techniques, including intravascular ultrasonography, require measurements to be performed at the leading edge of boundaries, never the trailing edge, is important. In muscular arteries such as the coronary arteries, frequently 3 layers exist.[23] The innermost layer consists of a complex of intima and internal elastic membrane. This innermost layer is relatively echogenic as compared to the lumen and media. The trailing edge of the intima (which would correspond to the internal elastic membrane) cannot always be distinguished clearly. Moving outward from the lumen, the second layer is the media. The third and outer layers consist of the adventitia and periadventitial tissues, respectively. The boundary separating the true adventitia from surrounding perivascular tissues is less well defined on intravascular ultrasonography images.

Lumen measurements

Lumen measurements are performed using the interface between the lumen and the leading edge of the intima. Generally, the leading edge of the innermost echogenic layer should be used as the lumen boundary. The following basic measurements can be recorded depending upon the operator’s preference:

• Lumen cross sectional area (CSA): The area bounded by the luminal border

• Minimum lumen diameter: The shortest diameter through the center point of the lumen

• Maximum lumen diameter: The longest diameter through the center point of the lumen

• Lumen eccentricity: 1 [(Maximum lumen diameter – minimum lumen diameter)/maximum lumen diameter]

• Lumen area stenosis: (Reference lumen CSA – minimum lumen CSA)/reference lumen CSA

The reference segment used should be specified as proximal, distal, largest, or average.

Further special measurements facilitated by intravascular ultrasonography are as follows:

• External elastic membrane measurements

• Atheroma measurements

• Calcium measurements

• Stent measurements (a postdeployment minimal stent area of 5 mm2 predicts increased likelihood of angiographic restenosis)

• Remodeling

• Length measurements

Atheroma morphology

Although intravascular ultrasonography cannot be used to detect and quantify specific histologic contents, certain image patterns can be very useful in estimating the morphology and content of the atheroma.

Soft (echolucent) plaques refer to the acoustic signal that arises from low echogenicity instead of plaque’s structural characteristics. Although a zone of reduced echogenicity generally results from high lipid content in a mostly cellular lesion, it could also result from a necrotic zone within the plaque, an intramural hemorrhage, or a thrombus.[23, 24]

Fibrous plaques have an intermediate echogenicity between soft (echolucent) atheromas and highly echogenic calcific plaques.[22] Generally, the greater the fibrous tissue content, the greater the echogenicity of the tissue.

Ultrasound imaging is more sensitive than fluoroscopy for coronary calcification detection.[25] Large calcifications may be associated with lesion stability. In contrast, microcalcifications are frequently found in lipid-rich necrotic core areas of unstable plaques and may not be well reflected in intravascular ultrasonography images.[26]

Plaques frequently contain more than one acoustical subtype.

A thrombus is usually recognized as an intraluminal mass, often with a layered, lobulated, or pedunculated appearance.[27] However, in vitro studies have revealed limitations of intravascular ultrasonography in the diagnosis of thrombi (sensitivity of 57% and specificity of 91%), considerably inferior to a conventional angiogram.[28] Intravascular ultrasonography is still unreliable in differentiating acute thrombi from echolucent plaques because of the similar echogenicity and texture of lipid-laden tissue, loose connective tissue, and stagnant blood.

The intimal hyperplasia characteristic of early in-stent restenosis often appears as tissue with very low echogenicity, at times less echogenic than the blood speckle in the lumen. Appropriate system settings are critical to avoid suppressing this relative nonechogenic material. The intimal hyperplasia of late in-stent restenosis often appears more echogenic.

Evaluating dissections and other complications after intervention

Intravascular ultrasound is commonly used to detect and direct the treatment of dissections and other complications after intervention. Intravascular ultrasonography allows for detailed classification of dissection and assessing the severity of the dissection. Additionally important characteristics of a dissection, such as the presence of a false lumen, the identification of mobile flap(s), the presence of calcium at the dissection border, and dissections in close proximity to stent edges are identified distinctly by intravascular ultrasonography.

Unstable lesions and ruptured plaques

Although no definitive features define a plaque as vulnerable on intravascular ultrasonography, a hypoechoic plaque without a well-formed fibrous cap is presumed to represent potentially vulnerable atherosclerotic lesions.[29]

In patients studied after an acute coronary syndrome, ultrasound imaging may reveal ulceration, often with remnants of the ruptured fibrous cap evident at the edges of the ulcer. Various other appearances are common, including fissuring or erosion of the plaque surface.

Unusual lesion morphology

Intravascular ultrasonography can be used to characterize unusual lesion morphology, such as aneurysms, pseudo-aneurysms, and true versus false lumens.

Ambiguous lesions

Intravascular ultrasonography lends itself to the identification of technically difficult lesions, such as intermediate lesions of uncertain stenotic severity or ostial stenosis and disease at branching sites. The application of intravascular ultrasonography in these circumstances depends on the interventionist. Intravascular ultrasonography can also be helpful for delineating lesions involving tortuous vessels and left mainstem lesions. Intravascular ultrasonography has a particularly important role in defining areas with intraluminal filling defects, angiographically hazy lesions, sites with plaque rupture, and lesions with local flow disturbances. Intravascular ultrasonography can be used to determine vein graft morphology in situ as well.

Of particular note is the role of intravascular ultrasound in establishing the mechanisms of in-stent restenosis. Restenosis after balloon angioplasty is largely driven by concentric geometric remodeling, with neointimal hyperplasia playing a lesser role. However, in-stent restenosis is almost exclusively the consequence of exuberant neointimal proliferation.[30, 29]

Intravascular ultrasonography measurement of minimum stent area is recognized as the most powerful predictor of long-term patency and clinical outcomes.[29] Intravascular ultrasonography observations were instrumental in the development of strategies to treat in-stent restenosis, including intracoronary brachytherapy. Most importantly, they led to the development of drug-eluting stents. Drug-eluting stents have dramatically reduced neointimal proliferation and the incidence of in-stent restenosis.[31]

Assessment of transplant vasculopathy

Posttransplantation coronary artery disease is the leading cause of death beyond the first year after cardiac transplantation, with a reported incidence of nearly 20% per year.[32] Intravascular ultrasonography not only allows assessment of early plaque accumulation before luminal stenosis develops in comparison to other diagnostic methods, but studies have also demonstrated an association between the severity of disease by ultrasound and clinical outcomes.[33] Patients with more severe disease on intravascular ultrasonography studies had an increased incidence of death, myocardial infarction, or retransplantation.[34, 35]

Aortic, carotid, and peripheral vascular disease

The role of intravascular ultrasonography in noncoronary vascular disease is expanding. The various unique limitations of traditional angiography in defining the anatomy of peripheral vessels can be circumvented by intravascular ultrasonography.[36] With routine angiography, often angulated or orthogonal views are not possible and foreshortening is not apparent. Heavy calcification in arteries deep within the thorax, abdomen, pelvis, and thigh can obscure the vessel borders even after digital subtraction. Intravascular ultrasonography can provide additional details on the lesion in such cases.

Nevertheless, several intravascular ultrasound artifacts or limitations are yet to be resolved, including catheter obliquity, limited spatial resolution in very large vessels, and severe acoustic shadowing by calcific plaque.