Basic Principles

IVUS imaging systems use reflected sound waves to visualize the vessel wall in a two-dimensional, tomographic format, analogous to a histologic cross-section. These systems use significantly higher frequencies than noninvasive echocardiography, achieving greater radial resolutions at the expense of limited beam penetration. The resolution, depth of penetration, and attenuation of the acoustic pulse by tissue are dependent on the geometric and frequency properties of the transducer. Current IVUS catheters used in the coronary arteries have center frequencies ranging from 20 to 45 megahertz (MHz), providing theoretical lower limits of resolution (calculated as half the wavelength) of 31 and 19 µm, respectively. In practice, the radial resolution is at least two to five times poorer (80 to 150 µm), determined by factors such as the length of the emitted pulse and the position of the imaged structures relative to the transducer. There are two basic catheter designs, based on solid-state or mechanical approaches (Fig. 58-1). Both types of catheters generate a 360-degree, cross-sectional image plane that is perpendicular to the catheter tip.

Figure 58-1 Diagrams of the two basic imaging catheter designs: solid-state (A) and mechanical (B).

Head-to-Head Comparisons

Mechanical systems have traditionally offered advantages in image quality compared with the solid-state systems because of the higher center frequencies and the larger effective aperture of a transducer element. Particularly, near-field resolution is excellent with mechanical catheters so that the digital subtraction of the ring-down artifact is not required. In addition, a stationary outer sheath of mechanical catheters allows the transducer to be moved through a segment of interest in a precise and controlled manner. Conversely, the longer rapid-exchange design of the solid-state catheter may track better than the short rail design of the mechanical systems in complex coronary anatomy. The distance of the transducer from the catheter tip is shorter than that of mechanical systems, which may also be beneficial in IVUS-guided intervention of chronic total occlusion (CTO) of lesions. The solid-state catheter includes no moving parts and, thus, is free from nonuniform rotational image distortion (NURD) (Fig. 58-2). This artifact can occur with mechanical systems when bending of the drive cable interferes with uniform transducer rotation, causing a wedge-shaped, smeared image to appear in one or more segments of the image. This may be corrected by straightening the catheter and motor drive assembly, lessening tension on the guiding catheter, or loosening the hemostatic valve of the Y-adapter.

Figure 58-2 Common image artifacts. A, A “halo” or a series of bright rings immediately around the mechanical intravascular ultrasound (IVUS) catheter (arrow) is usually caused by air bubbles that need to be flushed out. B, Radiofrequency noise (arrows) appears as alternating radial spokes or random white dots in the far-field. The interference is usually caused by other electrical equipment in the cardiac catheterization laboratory. C, “White cap” artifacts caused by side lobe echoes (arrows) originate from a strong reflecting surface, such as metal stent struts or calcification. Smearing of the strut image can lead to the mistaken impression that the struts are protruding into the lumen, potentially interfering with area measurements and the assessment of apposition, dissection, and so on. D, Non-uniform rotational distortion (NURD) results in a wedge-shaped, smeared appearance in one or more segments of the image (between 9 and 4 o’clock in this example).

Overall, however, in both systems, technical improvements are continuously being made, and good quality images can be achieved by either of them in the majority of cases. With both systems, serial cross-sectional images can be reconstructed into a longitudinal display mode, and both still frames and video images can be digitally archived on local storage memory or a remote server using Digital Imaging and Communications in Medicine (DICOM) Standard 3.0. Recently, both systems have begun installation directly into the cine-angiogram system, enabling operators to quickly and easily incorporate IVUS interrogations into their interventional procedures. With this preinstalled IVUS system, IVUS is always on and ready, obviating the need for console transport between labs. Additionally, the system’s tableside controller enables operator control of the device within the sterile field, facilitating direct investigation and exact location of a lesion of interest during the procedure.

Imaging Procedures

Before IVUS imaging, an intravenous injection of 5000 to 10,000 units of heparin or equivalent anticoagulation should be administered, as well as intracoronary (IC) nitroglycerine (100 to 300 mg), to reduce the risk for spasm. Mechanical catheters require a saline flush before insertion to eliminate any air in the protective sheath. Incomplete flushing can leave microbubbles adjacent to the transducer, resulting in poor image quality once the catheter is inserted (see Fig. 58-2). In either approach, image integrity should be checked before inserting the catheter. With a solid-state catheter, the catheter tip is first positioned in the aorta or a large proximal coronary vessel (not adjacent to any vessel wall) so that the ring-down artifact (a “halo” surrounding the catheter) can be electronically subtracted from the image before entering the coronary artery. If a significant ring-down artifact is observed with a mechanical catheter, microbubbles within the protective sheath may be suspected, requiring repeated saline flush procedures until the artifact is removed (see Fig. 58-2). The technique for delivering IVUS catheters is generally similar to that used for standard angioplasty or stent catheters. The imaging element is advanced distal to the area of interest, and the length of the target vessel is systemically scanned by withdrawal of the entire catheter (solid-state system) or by retracting the transducer within the protective sheath (mechanical system) over a standard 0.014-inch angioplasty guidewire. Automated pull-back devices withdraw the imaging element at a steady rate of 0.5 or 1.0 mm per second, which allows accurate axial registration of each cross-section for serial studies or precise longitudinal distance measurements.

Three-Layered Appearance of Arterial Wall

The interpretation of IVUS images relies on the fact that the layers of a diseased arterial wall can be identified separately. Particularly in muscular arteries, such as the coronary tree, the media of the vessel stands out as a dark band compared with the intima and adventitia (Fig. 58-3). Media are less distinctly seen by IVUS in elastic arteries such as the aorta and the carotid, so differentiation of the layers in those vessels can be problematic. However, most of the vessels currently treated by catheter techniques are muscular or transitional, and identification of the medial layer is usually possible (this includes the coronary, ilio-femoral, renal, and popliteal systems).

Figure 58-3 Intravascular ultrasound (IVUS) image (A) and schematic diagram (B) demonstrate the classic three-layered appearance of the intima (plaque), the media, and the adventitia. In many cases, the media can be difficult to resolve clearly in some portion of the image, but in this particular image, it stands out in all sectors. Note the speckled appearance of the blood within the lumen, particularly near the luminal border.

The relative echolucency of the media compared with the intima and the adventitia gives rise to a three-layered appearance (bright–dark–bright) (see Fig. 58-3). The lower ultrasound reflectance of the media is caused by the presence of less collagen and elastin than in the neighboring layers. Because the intimal layer reflects ultrasound more strongly compared with the media, a spill-over effect, known as “blooming,” is seen in the image. This results in a slight overestimation of the thickness of the intima and a corresponding underestimation of the medial thickness. Conversely, the media–adventitia border is accurately rendered because a step-up in echo reflectivity occurs at this boundary and no blooming appears. The adventitia and periadventitial tissues are similar enough in echo-reflectivity that a clear outer adventitial border cannot be defined.

Several deviations from the classic three-layered appearance are encountered in practice. In truly normal coronary arteries from young patients, echo-reflectivity of the intima and the internal lamina may not be sufficient to resolve a clear inner layer. This is particularly true when the media has a relatively high content of elastin. However, most adults seen in the cardiac catheterization laboratory (cath lab) have enough intimal thickening to show a three-layered appearance, even in angiographically normal segments. At the other end of the spectrum, patients with a significant plaque burden have thinning of the media underlying the plaque, often to the degree that the media is indistinct or undetectable in at least some part of the IVUS cross-section. This problem is exacerbated by the blooming phenomenon. Even in these cases, however, the inner adventitial boundary (at the level of the external elastic lamina) is generally identifiable. For this reason, most IVUS studies measure and report the plaque-plus-media area as a surrogate measure for plaque area alone. Adding in the media represents only a tiny percentage increase of the total area of the plaque.

Image Orientation

Another important aspect of image interpretation is determining the position of the imaging plane within the artery. The IVUS beam penetrates beyond the artery, providing images of perivascular structures, including the cardiac veins, the myocardium, and the pericardium. These structures have a characteristic appearance when viewed from various positions within the arterial tree, so they provide useful landmarks with regard to the position of the imaging plane (Fig. 58-4). The branching patterns of the arteries are also distinctive and help identify the position of the transducer. In the left anterior descending (LAD) coronary artery system, for example, the septal perforators usually branch at a wider angle compared with the diagonals; on the IVUS scan, the septals appear to bud away from the LAD artery much more abruptly compared with the diagonals. The combination of perivascular landmarks and branching patterns allows the experienced operator to identify the vessel and the segment from the IVUS image alone. It is also important to understand that with the current systems, the rotational orientation of an IVUS image as presented on the screen is arbitrary and can vary between imaging runs. Here again, the branching pattern and perivascular landmarks, once understood, can provide a reference to the actual orientation of the image in space. Some operators prefer to have a standard rotational orientation for each imaging run and take the time to adjust the presentation on the screen by rotating it electronically so that the branches always appear in a uniform position.

Figure 58-4 Perivascular landmarks. A, In the proximal portion of the left main coronary artery, a clear echo-free space filled with pericardial fluid, called the transverse sinus, is found adjacent to the artery, immediately outside of the left lateral aspect of the aortic root. B, In this distal cross-section from the left anterior descending (LAD) coronary artery, the right (R) and left (L) branches of the anterior interventricular vein (AIV) are seen to straddle the coronary artery. The pericardium appears as a typical bright stripe with rays emitting from it (arrows). C, At the level of the middle right coronary artery, the veins arc over the artery, typically at a position just adjacent to the right ventricular (RV) marginal branches. D, The great cardiac vein (GCV), running superiorly to the left circumflex (LCx) coronary artery appears as a large, low-echoic structure with fine blood speckle. Recurrent atrial branches emerge from the LCx artery in an orientation directed toward the GCV, whereas the obtuse marginal branches emerge opposite the GCV and course inferiorly to cover the lateral myocardial wall.

Quantitative Vessel Measurements

Unlike coronary angiograms, IVUS has an intrinsic distance calibration, which is usually displayed as a grid on the image. Electronic caliper (diameter) and tracing (area) measurements can be performed at the tightest cross-section, as well as at reference segments located proximal and distal to the lesion.⁴ In general, the reference segment is selected as the most normal-looking cross-section (i.e., largest lumen with smallest plaque burden) occurring within 10 mm of the lesion with no intervening major side branches. At lumen assessment, stagnant blood flow, the use of higher frequency IVUS, or both can increase the intensity of blood speckle, which may obscure the blood–tissue interface on a still image. A review of moving images can help identify the true lumen border. At procedure, saline can be injected through the guiding catheter to reduce blood speckle.

Vessel and lumen diameter measurements are important in everyday clinical practice, where accurate sizing of devices is needed. The maximum and minimum diameters (i.e., the major and minor axes of an elliptical cross-section) are the most widely used dimensions. The ratio of maximum diameter to minimum diameter defines a measure of symmetry. Area measurements are performed with computer planimetry. Lumen area is determined by tracing the leading edge of the blood–intima border, whereas the vessel (or external elastic membrane [EEM]) area is defined as the area enclosed by the outermost interface between the media and the adventitia. Plaque area (or plaque-plus-media area) is calculated as the difference between the vessel and lumen areas; the ratio of plaque to vessel area is termed percent plaque area, plaque burden, or percent cross-sectional narrowing. With the use of motorized pull-back, area measurements can be added to calculate volumes using Simpson’s rule.

Plaque Composition on Gray-Scale Intravascular Ultrasound

The early changes of atherosclerotic disease, the so-called “fatty streaks,” are too thin to be visualized with IVUS. As plaque continues to develop, it can be resolved on IVUS, with different acoustic properties, depending on the composition of the plaque. A plaque with extensive lipid infiltration has low echo-reflectivity (less than the adventitia) on IVUS. Plaques with predominantly fibrous tissue are more echogenic than fat-laden plaques and can cause signal attenuation to some degree. Calcified plaque is recognized by a bright interface that overlies a dark shadow extending radially outward (Fig. 58-5). This acoustic shadowing, often accompanied by “reverberations” (regularly spaced arcs deep to the initial bright interface), obscures the true thickness of the calcified plaque as well as any deeper tissue. Calcium is seen by IVUS in 60% to 80% of lesions undergoing intervention, only half of which are detected by fluoroscopy or angiography. A rough rule of thumb is that an arc of calcium must occupy two quadrants (180 degrees) on IVUS to be visible on fluoroscopy. Calcium on IVUS is seen more frequently with increasing age and in patients with stable (as opposed to unstable) angina, and correlates more with plaque burden than lesion severity. One of the major limitations of IVUS in tissue identification is the difficulty in discriminating thrombus from soft plaque, which has a similar signal, or “texture,” and brightness. IVUS clues to the presence of thrombus include (1) a nodular appearance or clefts in the tissue; (2) small channels within the mass; (3) scintillating appearance (reminiscent of amyloidosis on trans-thoracic echocardiography [TTE]); or (4) tissue that moves (wiggles) in response to motion of the vessel wall.⁴

Figure 58-5 Examples of coronary calcification. A, A rim of calcium is seen between 5 and 10 o’clock positions, located beneath a fibro-fatty plaque that tightly surrounds the catheter. Note the shadowing beyond the calcium. B, Superficial calcium (between 3 and 7 o’clock positions) at the luminal surface. Speckles within the lumen are signals from blood. C, Circumferential, “napkin ring” calcification. Two arcs of reverberation are seen (orange arrows), and another pair of reverberations is seen to the right of the arrows. The small bright point adjacent to the catheter at 8:30 o’clock (blue arrow) is guidewire artifact from this mechanical catheter.

Advanced Tissue Characterization

To enhance the accuracy of in vivo plaque characterization by IVUS, several advanced signal analysis techniques have been developed and introduced into the research and clinical arenas. Current commercialized systems attempt to identify tissue components directly or the deformability of the tissue (“palpography”) using computer-assisted analysis of raw radiofrequency (RF) signals in the reflected ultrasound beam.⁵ This analysis is based on the fact that there is greater information contained in the backscattered ultrasound signal than is revealed by the conventional amplitude-based image presentation alone. One system simply uses integrated backscatter values, calculated as the average power of the backscattered ultrasound signal from a sample tissue volume, to differentiate tissue types (IB-IVUS, YD Co., Ltd.). Two other systems employ spectral RF analyses with a classification tree algorithm developed from ex vivo coronary datasets (Virtual Histology™, Volcano Corporation) or a pattern recognition technique based on the degree of spectral similarity between the backscattered signal and a reference library of spectra from known tissue types (iMap™, Boston Scientific Corporation).⁶ All systems generate color-mapped images of the vessel wall, with a distinct color for each plaque component category (Fig. 58-6). When combined with automated pull-back and border detection techniques, these systems can provide a quantitative assessment of each tissue category over a three-dimensional coronary artery volume. Current technical limitations include limited spatial resolution (100 to 250 µm), no classifications for thrombus, blood, or intimal hyperplasia, and potential errors caused by poor ultrasound penetration through extensive calcification.

Figure 58-6 Examples of plaque characterization by radiofrequency intravascular ultrasound (IVUS) analysis. A, Virtual Histology™ (Volcano Corp.). Plaque components are determined using spectral radiofrequency signal analyses with a classification algorithm. Dark green, fibrous; light green, fibro-fatty; white, calcium; red, necrotic core. B, A color-mapped presentation of integrated backscatter values (IB-IVUS. YD Co., Ltd.). Blue, lipid pool; green, fibrous; yellow, dense fibrous; red, calcification. C, iMap™ (Boston Scientific Corp.). Classification of tissue is made based on the degree of similarity between the sample and reference frequency spectrum. This method enables confidence level (CL) assessment of each plaque component along with a color-mapped presentation superimposed on the corresponding gray-scale image.

All systems have demonstrated a correlation of IVUS-determined plaque compositions with corresponding histopathology of coronary specimens.⁵

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