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Year : 2003  |  Volume : 13  |  Issue : 1  |  Page : 53-60
Current trends and future applications of intravascular ultrasound


Department of Cardiovascular Radiology, All India Institute of Medical Sciences, New Delhi, India

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Keywords: Intravascular Ultrasound, Atherectomy, Stenting

How to cite this article:
Sharma S, Gulati G. Current trends and future applications of intravascular ultrasound. Indian J Radiol Imaging 2003;13:53-60

How to cite this URL:
Sharma S, Gulati G. Current trends and future applications of intravascular ultrasound. Indian J Radiol Imaging [serial online] 2003 [cited 2019 Oct 15];13:53-60. Available from: http://www.ijri.org/text.asp?2003/13/1/53/28628
Introduction

Catheter-based angiography is still the gold standard investigation to establish the diagnosis and guide interventional radiological procedures in vascular diseases. However, it has many limitations. Pathologic studies have revealed that angiographic interpretation frequently leads to an under or over estimation of the severity and extent of disease [1][2][3] Angiography depicts the arteries in a two-dimensional view of the contrast-filled lumen. Hence, any arbitrary projection can misrepresent the true extent of a stenosis, especially in the presence of eccentric disease [4]. The estimation of the degree of stenosis by angiography relies upon comparison with an uninvolved normal segment Autopsy studies demonstrate that there is no truly normal segment as the disease is usually diffuse in nature. In addition, angiography is limited in its ability to assess the disease mechanism and composition of the obstructive lesion.

Over the last decade, intravascular ultrasound (IVUS) has emerged as a new technique to assess vascular pathology IVUS refers to the acquisition of cross-sectional images of the target vessel by an ultrasound probe placed on the tip of an endoluminally positioned catheter.

Rationale for intravascular ultrasound imaging

The application of IVUS to vascular imaging has evolved, based upon several characteristics inherent to ultrasound technology. Due to the tomographic orientation of ultrasound, the full circumference of the vessel wall can be visualized, as compared with a two-dimensional view in angiographic studies. This enables comprehensive assessment of areas which are difficult to assess by angiography. These include diffusely diseased arteries, eccentric and ostial stenosis and angiographically foreshortened segment. Also, measurements can be performed during IVUS studies by using an electronically generated scale, thus, offering an advantage over stenosis estimation at angiography as the latter needs to be corrected for radiographic magnification [4],[5].

A unique feature of IVUS is its ability to provide qualitative information about plaque composition and its response to interventional strategies. The consistency of the plaque (soft, fibrous, calcific or mixed) and its differentiation from thrombus is well demonstrated by IVUS. Various studies have demonstrated a good correlation between histopathology of the atheromatous plaque and its echogenicity of IVUS [6],[7]. So far, IVUS imaging has been used mainly on for coronary interventions. The following description focuses on the present day role of IVUS in imaging and intervention in peripheral vascular disease and its applications in the future.

Technical aspects

The equipment required to perform intravascular ultrasound consists of two major components a catheter with a miniaturized transducer at its tip [Figure - 1] and a console containing the electronics necessary to reconstruct the image [Figure - 2]. The frequency of the ultrasound used is typically centered at 12.5 - 50 MHz. For vascular imaging of medium - sized vessels. Frequently 20 MHz is the most used frequency. Larger vessels such as the aorta require frequencies in the range of 12.5 to 20 MHz. Smaller vessels require higher frequency probes, in the range of 30-40 MHz. There are two types of catheter systems available, those with an end-hole which are delivered over the guide wire, and those which do not have an end-hole and are introduced directly through the sheath.

Although the reduction in transducer size results in a decrease in the resolution, this is partially compensated by the use of higher frequencies. Typically, the wavelength at 30 MHz is 50 um, yielding a practical axial resolution of = 150 um [8]. Determinants of lateral resolution are more complicated and depend on the imaging depth.

Two basic approaches to transducer design have been evaluated, viz phased-array and mechanical type. In the phased-array systems, multiple transducer elements (32-64) in an annular array are activated sequentially to generate the image. Mechanical probes use a drive cable to rotate a piezo electric transducer at 1800 rpm, yielding 30 images per second. The advantages and limitations of the two designs are compared in [Table - 1].

Image interpretation

A well-defined imaging protocol is vital for proper interpretation of IVUS images in the peripheral vascular tree. A slow pullback of the transducer from the distal to the proximal segments in the target vessel is the optimal way to acquire reproducible information about vessel architecture and catheter orientation. Most centers use a motorized pullback system to withdraw the catheter at a predetermined constant rate. Standard perivascular landmarks and side branches [Figure - 3] as seen on angiography and ultrasound are used to ensure that repeated measurements (eg. Pre- and post-intervention) are assessed at the same position within the artery.

Normal arterial anatomy : The generation of ultrasound images is based on the difference in the acoustic impedance of the layers of the vessel wall. Due to this difference, these layers reflect US differently.

Blood : [Figure - 4] On IVUS images, blood has a characteristic speckled pattern that is constantly changing in echogenicity with the cardiac cycle, being slightly more echogenic during systole [9]. In real-time imaging, sometimes the lumen/intimal interface may be difficult to distinguish when the blood flow is slow and stagnant, such as proximal to a severe stenosis. In such situations, the increased backscatter from blood may give the false impression of a thrombus or plaque. One more reason

for increased backscatter from blood may be the incorrect adjustment of the control for near field gain (time gain compensation or TGC). When the TGC is set too high, blood speckle becomes accentuated, masking the lumen / intima border [10].

Arterial wall [Figure - 4] The wall of the artery is composed of the intima, internal elastic lamina, media, external elastic lamina, and adventitia. The intima consists of a monolayer of endothelial cells which in itself is beyond the resolution of current ultrasound catheters. However, if there is intimal hyperplasia, it may be detected as a thin echogenic layer [11]. The internal elastic lamina is seen as the innermost thin echogenic layer [7]. Because of its high echogenecity, the actual thickness of the layer may be overestimated (a phenomenon referred to as blooming), which may sometimes make it difficult to distinguish from mild intimal proliferation [11]. The outermost layer i.e the adventitia is collagen-rich and is, thus, bright in appearance.

The echogenecity of the media depends upon the relative content of smooth muscle on one hand, and collagen and elastin on the other. The latter are strongly echoreflective, and in objective terms, the reflectance of collagen is about 1000 times more than that of muscle [10]. The relative composition of the media is different for the elastic and muscular arteries. The aorta, pulmonary artery, and the proximal segments of the brachiocephalic, carotid, subclavian and common iliac arteries belong to the elastic type. All other arteries such as the coronary, renal and femoral are the muscular type.

The media of the muscular arteries is composed largely of smooth muscle cells and is thus poorly echoreflective, forming a large acoustic mismatch between the surrounding layers, resulting in a three-layered appearance on the US image [12]. Large elastic arteries have a media that contains a higher relative amount of collagen and elastin which make this layer strongly echoreflective. Hence, the distinction between the three layers is less marked, resulting in a two-layered appearance [13].

Appearance on IVUS in various disease states :

Various studies have compared the ultrasound appearance of the plaque to histology in freshly explanted human arteries [13],[14]. Currently IVUS is the most reliable imaging modality that identifies the composition of arterial plaques.

Gussenhoven et al [15] proposed that there are essentially four basic relationships between plaque composition and its echogenecity on IVUS : hypoechoic, representing a high lipid content of plaque, soft echoes, representing fibromuscular tissue, hyperechoic, representing collagen-rich (fibrous) plaque; and hyperechoic with lack of through transmission, representing calcium. Hodgson et al [16] studied IVUS morphology in human coronary arteries and correlated the image obtained with angiography. They classified IVUS images into 5 morphological subtypes, soft, fibrous, calcific, mixed and concentric subintimal thickening [Figure - 5][Figure - 6]. They found that on comparison with patients with stable angina, those with unstable angina had more soft lesions (greater lipid content ) (74% vs 41%), fewer calcified and mixed plaques (25% vs 54% or 49%) and intralesional calcium deposits (16% vs 45%). IVUS demonstrated a greater sensitivity than angiography for identifying unstable lesions (74% vs 40%). These observations have important implications for peripheral vascular disease as well. It is the plaque composition, rather than the severity of the stenosis, that predicts the vulnerability of a lesion to rupture and produce acute symptoms. This information is most reliably provided by IVUS [Figure - 7].

Plaque measurements : Atheroma area is determined by planimetry of the intimal leading edge and external elastic lamina (EEM) area occupied by the atheroma. This quantitative ultrasound measurement is usually substantially greater than that made on angiography due to two major reasons, the diffuse nature of the disease affecting even the angiographically "normal reference sites", and the expansion of the EEM which occurs as a response to atherosclerosis (known as positive remodeling) [17],[18] and maintain a constant luminal area during the early stages (the Glagov effect).

The majority of plaques are seen to be eccentric in location on IVUS studies [Figure - 8]. This observation has important implications for guiding interventional procedures, particularly for directional atherectomy and other selective plaque removal techniques. In some vessel segments, instead of vessel expansion, vessel shrinkage may occur, which has been referred to as de-remodelling or negative remodeling. This may actually contribute to luminal stenosis. Recently, this phenomenon has been implicated in restenosis after interventional procedures [19].

Other disease states

Thrombus : Thrombus is echogenic and may be difficult to distinguish from a noncalcified fibrous plaque or stagnant blood. It, however has a typically scintillating or sparkling pattern on real-time US examination. The presence of microchannels, and an echodensity of less than 50% of the adventitia are important clues to its correct identification [20],[21].

False Lumen : A false lumen may occur spontaneously or commonly following endovascular interventions. Mistaking a false lumen for true lumen can have serious consequences if the former is selected for stent or stent-grafti placement (as in aortic dissections) IVUS may help in such situations by recognition of the characteristic three-layered appearance of true lumen identification of side branches taking off from the true lumen and by the slow flowing, more echogenic blood within the false lumen. In addition, flush injections of contrast may at times reveal the echogenic patterns of the contrast to "hang-up" and take longer to evacuate from the false lumen compared to the true lumen.

Aneurysm : A true aneurysm is differentiated histologically from a false aneurym, by the presence of media in the former. IVUS can detect the presence of hypoechoic media to distinguish the two entities, although at times the media may be very thinned out.

Nonspecific aortoarteritis : We have reported the IVUS imaging findings in Takayasu's arteritis [22]. The intima is relatively unaffected and remains thin. There is an increase in the echogenecity and thickness of the media.

The adventitia is also similarly affected with diffuse periarterial fibrosis [Figure - 7][Figure - 10]. Due to these changes, the characteristic three-layered appearance may not be seen at places. In addition, the lesions can be complicated by the presence of calcification. The compliance of the aortic wall is lost in the involved segments on real-time imaging [Figure - 11]. These changes are seen even in the angiographically "normal" segments of the vessel, emphasizing the diffuse nature of involvement by the disease. This observation has important therapeutic implications. Correct demonstration of normal segments helps in choosing the sites for placement of proximal and distal anastamosis in bypass grafting at surgery and for optimal positioning of the balloon catheter or stent and interventional radiological treatment. IVUS helps in making this decision and has the potential to improve the long term results of the above treatment methods.

Clinical applications

1. Quantitative ultrasound : Angiography permits only monoplanar assessment of the lumen diameter and results in an underestimation of the disease. IVUS allows planimetric measurement of the artery lumen as well as the vessel wall area and overcomes this limitation.

2. Balloon angioplasty : Percutaneous transluminal angioplasty (PTA) acts by the creation of cracks and dissection of atherosclerotic plaque with localized medial dissection. This has been clearly demonstrated by IVUS studies [23]. Concentric lesions that dissected during PAT achieved a greater luminal gain compared to those that did not dissect or were eccentric in location [24]. The detection of a large intimal flap created during PTA mandates a repeat prolonged inflation or stent placement. Hence, the use of IVUS can help determine the end-point of angioplasty. An accurate determination of the balloon size is enhanced by using IVUS images to measure the vessel diameter. In addition, IVUS can also help in selecting an appropriate recanalization technique by virtue of its ability to differentiate a stenosis produced by thrombus, plaque or mural abnormality. The amount and distribution of calcium may have a significant impact on the outcome of angioplasty procedures [25]. This can be reliably detected by IVUS [Figure - 12]. Compliant lesions without a definite fibrocalcific structure are more likely to have elastic recoil following PTA, whereas large calcific deposits may predispose to a more severe tear of the vessel wall. IVUS is helpful after PTA when pressure gradients still exist despite a satisfactory angiogram as it provides a direct anatomical assessment of the residual stenosis. Angiography consistently underestimates the degree of residual narrowing even when performed in multiple projections [26].

3. Stenting : Endovascular stenting is performed for complex lesions, total occlusions, or in cases with suboptimal response or obstructive dissection following PTA. Due to the brightly echogenic appearance of the metal struts, stents are easily recognized on IVUS. IVUS is extremely valuable in assessing the degree of apposition of the stent to the vessel wall. This information is not obtained on angiography [27]. In cases with incomplete apposition, balloon dilatation within the stent should be performed. This is important since any space left between the stent and the endothelium will be occupied by thrombus, delaying the ingrowth of the endothelium to cover the inner surface of the stent.

4. Atherectomy : For atherectomy, it is important to know the location and depth of the plaque as well as the presence of significant calcification. Ultrasound imaging can identify superficial calcium which is associated with poor tissue retrieval. The sizing of the atherectomy device is crucial, since a device which is undersized will leave a significant residual plaque burden, whereas one that is oversized may shear or cut into the media and adventitia, potentially leading to vessel rupture or formation of a pseudoaneurysm. Deep intimal tearing also predisposes to accentuated intimal hyperplasia and significant restenosis following the procedure [25],[28]. In this respect, the planimetric information obtained from IVUS is helpful to select the ideal size of the atherectomy device. The most striking finding from IVUS studies in the context of directional atherectomy is the substantial residual plaque burden following the procedure, consistently demonstrated with IVUS in cases where the angiographic result seems to be optimal [29]. This has highlighted the issue of more aggressive plaque removal on the basis of ultrasound imaging, allowing the safe use of large burrs with a greater subsequent luminal gain.

5. Stent-graft placement : For endovascular treatment of aneurysms, it is imperative to know the diameter of the proximal and distal necks to select the correct size of the stent graft. If the device is too small, endoleaks may occur post-procedure from the proximal or the distal end. This sizing is accurately done with the cross-sectional measurement performed with IVUS. Also, during the procedure, complete apposition of the stent struts or hooks to the vessel wall can be confirmed with IVUS imaging. This can be accurately assessed with angiography. For a stent-graft placed for the treatment of aortic dissection, the sealing of the site of entry tear is most reliably confirmed only with IVUS imaging.

6. Vena cava filter : Whenever technical problems (filter tilting or filter migration) or complications (caval thrombosis or recurrent pulmonary embolism) of filter placement are suspected. IVUS may be used to complement or obviate cavography. It is also possible to perform the entire procedure under IVUS guidance, since the identification of renal veins is easy with this technique.

7. Mechanisms of restenosis : Insights with IVUS imaging : In the early years of interventional techniques, it was believed that the predominant mechanism of restenosis was intimal hyperplasia. Following angioplasty, this would occur with a deep extension of the dissection, exposing the media to blood and initiating an aggressive platelet response which results in intimal proliferation [25]. With atherectomy, IVUS may sometimes demonstrate a scalloped outline of the lumen, predisposing to increased local turbulence which causes greater platelet aggregation and restenosis [30]. However, Pasterkamp et al [31] studied peripheral vessels with IVUS and observed that shrinkage of the vessel or negative remodeling was another major mechanism contributing to late lumen loss. In another study on coronary interventions [32], decrease in the EEM area contributed to 70% of the luminal loss, whereas intimal proliferation was responsible for only 23% of the loss. The restenotic response occurring following stent placement is different in that it is primarily due to neointimal hyperplasia. This is probably because stents can resist the remodeling process [33]. This, combined with the fact that stents results in greater initial luminal expansion, contributes to a lower later restenosis rate with stenting compared to balloon angioplasty or atherectomy.

8. Miscellaneous applications :

a. In case of aortic dissection, IVUS has been shown to be superior to angiography and transesophageal echocardiography in identifying the points of entry and re-entry [34].

b. Percutaneous fenestration of aortic dissection has been accomplished successfully using IVUS as the guiding imaging modality. Identification of the highly echogenic needle as it passes from one lumen into the other is easily monitored with ultrasound.

c. IVUS can be employed for assessing progression of plaque, where it is superior to angiography [35].

d. Tissue characterization is possible with ultrasound imaging based on the differential acoustic impedance properties of the various layers of the vessel wall. This may have a role in patients with Marfan's syndrome (abnormalities in the elastin content) where IVUS may be used for diagnosis and follow-up [36].

e. IVUS has the capability to study the cardiac chambers, wall motion abnormalities and valve movements [37].

f. Endoluminal sonography has been used for evaluation of gastrointestinal and genitourinary tract as well as tracheobronchial tree to image a variety of abnormalities [38][39][40].

i. Uses in the gastrointestinal tract include distinguishing between various submucosal lesions, assessing the severity of oesophageal varices and evaluating fibrosis in scleroderma

ii. In the genitourinary tract, endoluminal US has been applied for the diagnosis of upper urinary tract calculi, tumors and mural abnormalities as well as an adjunct to endourological procedures. It has been experimentally employed in the imaging of tubal abnormalities.

iii. In the tracheobronchial tree, it has been applied as a guide for biopsy of lymph nodes and tumors not visualized on routine bronchoscopy.

Limitations of intravascular ultrasound

1. With the current resolution and processing available with IVUS devices, it may be difficult to differentiate a thrombus superimposed upon a plaque from a soft, lipid laden plaque.

2. In tortuous vessels, there may be under - or overestimation of the disease due to inability to maintain a constant catheter - vessel coaxial alignment.

3. Calcific / fibrous lesions may cause echo drop outs, hindering the visualization of the underlying plaque.

4. The high cost of equipment may be inhibitory to a majority of interventionists, who are still not comfortable with its use.

Future directions

New and creative areas of IVUS applications are being explored. Doppler capabilities are being incorporated within IVUS catheters to allow for simultaneous hemodynamic assessment of the stenosis. Real-time three-dimensional reconstruction of IVUS data, by providing information about spatial relationships of anatomical structures may enhance the capabilities of IVUS. Continued improvements in transducer design and technology will allow for better resolution and penetration of US waves. Improvements in catheter trackability and steerability should allow for easier catheterization of tortuous vessels and side branches that are presently difficult to select.

One of the key issues for the future of IVUS for its induction in the interventional sites is the demonstration of a clear clinical benefit [41]. Two kinds of studies are currently being initiated, those that analyze the effect that IVUS imaging has on decision making of the operator during the therapeutic procedure, and those that evaluate the impact of this modality on the long-term outcome of endovascular interventions. There are also studies engaged in developing and testing prototypes of combined imaging/stent delivery and imaging / atherectomy devices. These would significantly reduce the procedure time and give an 'on line' assessment of plaque orientation and changes occurring with the device. Ultrasound may have the potential to be used for pulverizing plaque or thrombus and creating a channel whereby a subsequent angioplasty can be performed. It may even be used as a sole therapeutic modality using higher energies, thus bringing down the cost and time of clot lysis procedures.

Endoluminal sonography, especially the three-dimensional reconstruction algorithms, may open new vistas in gastroenterological imaging, such as in the treatment of inflammatory bowel disease, staging of rectosigmoid neoplasia and pancreatobiliary disease processes. It may be an adjunct to imaging and intervention in endometrial cervical and prostatic tumors.

 
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Correspondence Address:
S Sharma
Department of Cardiovascular Radiology, All India Institute of Medical Sciences, New Delhi
India
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12]

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