State of Art Paper
 

Real-Time Three-Dimensional Echocardiography: A Current View of
What Echocardiography can provide?
*Fadi G. Hage, **Navin C. Nanda
*Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL.
**Section of Cardiology, Birmingham Veteran’s Administration Medical Center, Birmingham, AL

Abstract
The development of real-time three dimensional echocardiography has allowed for the incorporation of 3-
dimensional echocardiographic imaging into everyday cardiovascular clinical practice. In this State of the Art
Paper we will provide an overview of three dimensional echocardiography and specific indications in which
it has incremental value over traditional 2-dimensional echocardiography.
Keywords: Three-dimensional echocardiography; valvular disease; cardiomyopathy; congenital heart disease;
cardiac thrombus; cardiac tumor.

Real-time three dimensional echocardiography (3DTTE) is the latest advancement in a succession of breakthroughs in the use of ultrasound to image the heart. It is therefore appropriate to view 3DTTE as a natural step in the evolution of echocardiography from M-mode to 2-dimensional (2D), followed by the addition of Doppler and Color Doppler and the recent introduction of tissue Doppler, speckle imaging and contrast echocardiography1,2. In the tradition of its predecessors, this new technique has proven useful, versatile and revolutionary in the assessment of cardiovascular diseases. In this State of the Art Paper, we will provide an
overview of 3DTTE and specific indications in which it has incremental value over 2DTTE and/or 2D transesophageal echocardiography (2DTEE).
HISTORICAL PERSPECTIVE
The advent of 2DTTE revolutionalized noninvasive imaging, but its limitations in clinical practice soon became clear because it only provided images resembling thin slices of cardiac structures. This led to several attempts to develop 3D echocardiography3-8. Morris and Shreve9 introduced a spark gap position-locating approach to provide 3D coordinates but this method could not actually record or view 3D images. Another approach developed by Ghosh et al8 utilized placing the 2D transducer at the cardiac apex and rotating it every few degrees in a sequential manner to obtain multiple slices of the heart which were then reconstructed by computer to obtain 3D images of the left ventricle (LV). The volumes

obtained using this method were validated by angiography. Raqueno et al10 and Schott et al11 successfully incorporated velocity information and color Doppler reconstruction in the apical rotation technique. The introduction of TEE with its superior image quality provided further impetus and led to the development of 3DTEE imaging. Using a monoplane TEE probe, transverse sections at various cardiac levels were obtained by moving the probe contained in a carriage up and down the esophagus which were reconstructed to provide 3D images12,13. The large size of the probe, however, precluded routine clinical use. Attempts at 3D imaging were made using a regular biplane TEE probe14. With the probe angulated at 900, it was rotated in small increments to provide sequential longitudinal
images which were reconstructed in 3D since their spatial orientation and relationship to each other could be determined. Subsequently, Nanda et al15 used a multiplane TEE transducer to create 3D images by keeping the probe stationary at a given level and rotating it few degrees at a time. This method was used by several investigators to provide clinically useful incremental information over 2D imaging and even resulted in the publication of a book with contributions from many investigators around the world16. A limitation of this technique was the acquisition of images over several cardiac cycles which took some time and produced artifacts due to changes in heart rate, and patient or probe motion during the procedure. To obviate this problem, live/RT 3DTTE and subsequently 3DTEE imaging were developed and remain the mainstay of

Correspondence: Navin C. Nanda, University of Alabama at Birmingham, Heart Station SW/S102, 619 19th Street South, Birmingham, AL 35249
Email: nanda@uab.edu

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3D echocardiography as it is currently practiced in the clinical setting. Initial attempts resulted in the development of a stand alone system which provided only B-mode images17. Later, a matrix probe was developed and incorporated into the regular ultrasound system to provide both B-mode and
color Doppler live/RT 3D images facilitating its use in dayto- day clinical practice18. Subsequently, the transducer was made much smaller and incorporated in the TEE probe providing superior quality 3D images. Initial clinical results using real time 3DTEE were first published in the year 200719.
EXAMINATION PROTOCOL
In order to generate 3D images, the phased array transducers utilize a 2D sector, which is similar to the sectors echocardiographers are accustomed to with 2DTTE, that travels along the Z-axis which is perpendicular to the sector

plane. Using 3DTTE, the echocardiographer can display the images as a narrow sector (60Úx30Ú) that allows for real time imaging with beat-to-beat variability, or by combining 4 smaller sectors together as a ‘full-volume pyramidal dataset’ (60Úx60Ú). This pyramidal dataset can, in almost all settings, contain the whole area of interest in a single view without the need to move the transducer. The echocardiographer can then dissect the pyramidal dataset using cropping planes for 2D views from any desired angle either in RT or later on in the off-line mode. Since the images obtained more closely resemble actual anatomy than 2DTTE, they are more amenable to manipulation in 3D space in order to derive the needed clinical information. The current accepted protocol for 3DTTE relies heavily on the standard 2DTTE views, familiar to all echocardigraphers, in addition to anatomical orientation to facilitate and standardize the interpretation of the examination (Figure 1)20.

Figure 1. 3DTTE uses cropping planes for anatomical sectioning of the heart therefore allowing for 6 different perspectives for any cardiac structure (A).
The cropping can be performed from the left or the right in the sagittal plane (B), from above or below in the coronal plane (C), from the base or the apex
in the transverse plane (D), or from non-standard planes that can be used for the best visualization of the structure of interest. Reproduced with permission
from Nanda et al. Examination protocol for three dimensional echocardiography. For Adhoc 3D Echo Protocol Working Group Echocardiography
2004;21:763-768.
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EVALUATION OF VALVULAR DISEASE
Mitral Valve
The mitral valve is a geometrically complex structure; the mitral annulus has a saddle-like shape, the posterior leaflet consists of three scallops (P1, P2, and P3 being the anterolateral, middle and posteromedial scallops respectively), and the anterior leaflet which can be symmetrically divided into three segments (A1, A2, and A3 being the anterolateral, middle, and posteromedial segments)21-23. 3DTTE has gained superiority over its 2D counterpart in the evaluation of mitral valve pathology since the latter modality struggles in the visualization of this complex 3D structure in 2D space. The assessment of mitral stenosis by 2DTTE is limited by the indirectness of the pressure half-time method and the difficulty in assuring that the plane of planimetry is parallel to the valve orifice at the level of the leaflet tips24-26. 3DTTE has a demonstrable advantage in this regards, not only due to the ability to orient the imaging plane in the 3D pyramidal dataset in such a manner as to be absolutely certain that the planimetered area is that of the flow-limiting orifice, but also due to its ability to evaluate the subvalvular apparatus and check for the presence of a thrombus in the left atrial appendage, therefore avoiding the need for a TEE27, 28. A direct measurement of the mitral valve area with 3DTTE is therefore a better assessment of mitral stenosis than 2DTTE and can be used even in situations where the 2D examination is limited such as after balloon valvuloplasty27-31. An accurate quantitative assessment of mitral regurgitation severity by 2DTTE can be challenging due to the several assumptions used in the calculations32-34. By using 3DTTE, the vena contracta can be captured in a 3D pyramidal dataset and cropped to the level of the mitral valve leaflet tips in a plane that is parallel to the orifice. Rotating the image will show the vena contracta en face and allow for measuring its area without the often invalid assumption of a circular or elliptical shape used in 2DTTE formulas. This technique provides a load independent assessment of the regurgitant orifice that compares better than the invasive angiographic and traditional 2DTTE measurements35. Since the 3D dataset contains the entire mitral valve apparatus, a comprehensive evaluation of the leaflet geometry can be done to assist in surgical planning and in identifying flail leaflets, chordae rupture and endocarditis as causes of acute mitral regurgitation36,37. Furthermore, an accurate and precise identification of the segment or the scallop that is involved in mitral valve prolapse is possible with 3DTTE and therefore can help in determining suitability for repair23,31,38,39. Aortic Valve The use of 2DTTE with Doppler can lead to underestimation or

overestimation of the severity of aortic stenosis40-42. These errors are usually compounded in the calculation of the aortic valve area due to any inaccuracy in measurement of the LV outflow tract diameter which is squared in the continuity equation. Direct measurement of the flow-limiting aortic valve orifice is possible with 2DTTE and 2DTEE but suffers from the same limitations that are faced with mitral stenosis in aligning the imaging plane with the orifice43. Using methods similar to the ones described for mitral stenosis, the aortic valve orifice can be visualized and measured en face by aligning the imaging plane exactly parallel to the aortic valve orifice in the short-axis view which can be quite useful in patients with domed valves and angulated orifices. These measurements with 3DTTE correlated better with intraoperative 3DTEE reconstruction measurements than with 2DTTE or 2DTEE. Furthermore, it correctly classified surgically confirmed severe aortic stenosis cases that were missed by 2DTTE44. This incremental value of 3DTTE over 2DTTE has now been demonstrated by multiple investigators45,46. Although there are several quantitative methods to gauge the severity of aortic regurgitation on 2DTTE, the most reliable and
commonly used depends on measuring the width of the vena contracta. Nevertheless, since only a single dimension of the vena contracta is seen on the parasternal long axis and apical 5 chamber views it would require often invalid geometric assumptions to determine the area of the vena contracta. On the short axis view, the vena contracta can be seen en face but it is difficult to determine whether the imaging plane is parallel and at the exact level of the vena contracta47. These serious errors in measurement can be avoided with the use of 3DTTE as outlined for mitral regurgitation. Grading the severity of aortic regurgitation has thus been shown to correlate better with invasive angiography than 2DTTE48. Tricuspid and Pulmonary Valves Unlike mitral stenosis, imaging the tricuspid valve in short axis to determine the severity of tricuspid stenosis is rarely possible by 2DTTE but quite feasible with 3DTTE. Also since all 3 leaflets can be seen on 3DTTE, prolapsing segments and flail leaflets can be easily identified49. Using color Doppler tricuspid and pulmonary regurgitation can be accurately quantified through the measurement of the area of the vena contracta34,50. EVALUATION OF VENTRICULAR
FUNCTION AND THE
CARDIOMYOPATHIES

The most common sought after finding from an echocardiogram is the Left Ventricular Ejection Fraction (LVEF). Regardless of its multiple limitations, a quantitative measurement of LVEF that is accurate and reproducible is invaluable for the management of cardiac patients. Despite the advent of several other imaging

   
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modalities, 2DTTE remains the most commonly used to measure LVEF. The various methods used by 2DTTE for this purpose are limited by observer variability, reliance on geometric modeling, and foreshortening51,52. Current 3DTTE software allow for the quick and direct measurement of LVEF from a 3D dataset that encompasses the entire LV without the need for geometric modeling. Additional advantages of 3DTTE include the ability to measure LV volumes and LV mass. These measurements have now been widely validated by multiple investigators and against different standards including magnetic resonance imaging51,53-56. In addition, 3DTTE can be used for the
assessment of right ventricular function57,58. Besides its demonstrable advantage over 2DTTE in measuring LVEF, 3DTTE has been useful in the evaluation of various cardiomyopathies. In patients with isolated left ventricular noncompaction, 2DTTE usually reveals multiple prominent trabeculations, most commonly in the apical portion of the LV, and with the use of Color Doppler, deep intertrabecular recesses that communicate with the LV cavity59. Using 3DTTE, the honeycomb appearance that is typical of non-compaction can be seen even in patients in whom 2DTTE is non-diagnostic60. Furthermore, because patients with non-compaction are at high
  Figure 2. 3DTTE with color Doppler for assessment of vena contracta area. Three-dimensional color Doppler data set showing mitral regurgitation (MR, A) is cropped from top to the level of the vena contracta (arrowhead, B) and tilted to view it en face (C, D). The vena contracta is then planimetered by copying onto a videotape. LA=left atrium; LV=left ventricle. Reproduced with permission from Khanna D et al: Quantification of Mitral Regurgitation by Live Three- Dimensional Transthoracic Echocardiographic Measurements of Vena Contracta Area. Echocardiography 2004;21:737-743.  
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risk of thromboembolic events, 3DTTE has been found to be more suitable than 2DTTE to detect the presence of LV clots since on 2DTTE it can be difficult to differentiate clots from trabeculations61,62. More recently, Rajdev et al studied 21 patients with LV non-compaction using 2DTTE and 3DTTE and showed that 2DTTE can underestimate the extent of non-compaction due to the complex geometry of the trabeculations and the limited view of 2DTTE to one plane at a time unlike the more comprehensive assessment by 3DTTE63. Unlike 2DTTE, 3DTTE can help in differentiating hypertrophic cardiomyopathy from other forms of LV hypertrophy (such as that seen with systemic hypertension or in trained athletes) and can provide more accurate determination of LV mass and volume64,65. It can also be helpful in pinning the diagnosis of apical hypertrophic cardiomyopahy which is often elusive on 2DTTE66, and in the assessment of the severity of LV outflow obstruction67. Our group has also showed that 3DTTE can be very useful in following the improvement in diastolic function seen in these patients after alcohol septal ablation (Figure 3)68 .
EVALUATION OF CONGENITAL HEART
DISEASE

Although 2DTTE is the most widely adopted imaging modality for the evaluation of congenital heart disease patients, it suffers from the limitation of visualization of complex 3D lesions in 2 dimensions. With the advent of 3DTTE, the echocardiographer is given the opportunity to visualize these lesions in a manner not different than computed tomography or magnetic resonance imaging in a completely non-invasive setting that requires little cooperation from the patients and avoiding the risk of potentially harmful radiation in mostly young individuals. Atrial septal defects, patent foramen ovale and ventricular septal defects are common congenital heart disease lesions that are traditionally imaged with 2DTTE. Recently, percutaneous defect closure has been developed as a viable alternative to surgical correction of these lesions69,70. Although the indications to undergo percutaneous or surgical repair are similar, considerations that are important for the success of a percutaneous approach include the location of the defect, its shape and size and the adequacy of its margins for the placement of such devices69,71,72. Since these defects cannot be visualized ‘en face’ by either 2DTTE or even 2DTEE, the maximum dimension and the geometrical shape can’t be determined with certainty. Therefore, 3DTTE is at a theoretical advantage in the assessment of the size, shape and suitability of these lesions for percutaneous closure73-75. 3DTTE can also be useful for the efficacy of percutaneous closure devices and the detection of post-closure complications such as residual shunts device malposition, embolization and fracture74,76. 3DTTE has also been used for the study of the more complex
Figure 3. Left atrial ejection fraction (LAEF) as measured by 3DTTE in 12
individual patients with hypertrophic cardiomyopathy before and after
alcohol septal ablation (ASA). The LAEF showed a significant improvement
from 43.1 ± 9.0% before to 52.5 ± 8.8% after AISA (P=0.001). Reproduced
with permission from Hage FG, et al. Effect of alcohol-induced septal
ablation on left atrial volume and ejection fraction assessed by real time
three-dimensional transthoracic echocardiography in patients with
hypertrophic cardiomyopathy. Echocardiography 2008;25(7):784-789
 
ostium primum defects since, unlike 2DTTE, it is able to evaluate the number and size of all 5 individual leaflets of the common atrioventricular valve and the atrial septal defect therefore providing a better subclassification of these defects than 2DTTE77. Furthemore, since with 3DTTE complex conduit tracking is possible, it has been used for the visualization of patent ductus arteriosus, for the selection of patients for percutaneous correction, and for the diagnosis of complications from the placement of occluder devices78,79. 3DTTE has also shown its superiority over 2DTTE for the imaging of multiple congenital heart disease lesions including coronary anomalies80,81, Ebstein’s anomaly82, cor triatriatum sinister83, Chiari network84, and others.
EVALUATION OF CARDIAC MASSES
3DTTE has a distinctive advantage over 2DTTE in the assessment of cardiac masses in its ability to visualize the interior of the mass. Since the entire mass can be included in the 3D dataset, cropping of the mass can provide a unique view of its interior composition which can reveal information about its nature85-89. In the case of thrombi, such a look can reveal areas of echolucency in the clot which indicate the beginning of clot lysis62. Since clots start to dissolve from inside to out, this information which is not available on 2D examinations can clearly have therapeutic and
prognostic implications (Figure 5). Furthermore, 3DTTE can show the exact point of attachment of the thrombus and define its mobility and therefore estimate its propensity to embolize62. 3DTTE has shown great promise in the evaluation of the left atrial appendage. Historically, 2DTEE has been the method of
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choice to reliably exclude the presence of a thrombus in the left atrial appendage. We recently reported our experience with the use of 2DTTE, 2DTEE and 3DTTE in 92 patients as well as 2DTTE and 3DTTE in another 20 patients who had contraindications or other considerations that prohibited the use of 2DTTE86. The left atrial appendage was well visualized with 3DTTE in all patients and was able to identify the thrombus in all patients diagnosed to have a clot by 2DTEE. Furthermore, in 11 patients who were thought to have a clot by 2DTEE, 3DTTE
 
Figure 4. The evaluation of ventricular septal defect with 3DTTE. (A,B)
The arrowhead shows a defect in the ventricular septum (S). P represents
the dehisced patch. C,D: En face view of the defect (arrowhead) without
(C) and with (D) color Doppler flow signals. LV=left ventricle; RV=right
ventricle. Reproduced with permission from Mehmood F, et al. Usefulness
of live/real time three-dimensional transthoracic echocardiography in
the characterization of ventricular septal defects in adults.
Echocardiography 2006;23(5):421-427.
 
revealed the absence of a clot and the presence of a prominent transversely oriented pectinate muscle. In the 20 patients that could not have 2DTEE, a clot was seen in 1 patient while the other 19 underwent cardioversion for atrial fibrillation with no complication. Therefore, 3DTTE can have a role in evaluating for the presence of a left atrial appendage in patients not eligible
for 2DTEE, as well as to confirm the presence of a mass lesion seen on 2DTEE86. 3DTTE can also be used to examine for the presence of clots in the right atrium and on pacemaker leads and vascular catheters87,88. In the case of cardiac tumors, an inside look at the structure of the mass from within can provide a clue to the diagnosis. For example, fibromas are typically dense, homogeneous masses with central liquefaction while myxomas have localized echoluscent areas consistent with necrosis or hemorrhage89.
Hemangiomas are vascular tumors which on 3DTTE show more extensive and vascular areas with little solid tissue89,90. Chordomas have multiple echodense areas consistent with fibrosis and scattered echolucencies91. Sarcomas demonstrate echolucent areas consistent with necrosis and dilated vessels surrounded by dense fibrosis that show as hyperechoic bands giving the appearance of a “doughnut”92. In the case of hydatid cysts, the 3DTTE can show the granddaughter cysts budding from the daughter cysts as well as great-granddaughter cysts from granddaughter cysts93. Since these cardiac tumors can have complex geometric shapes, 3DTTE has a distinctive advantage over 2DTTE in their evaluation and can determine the location of the attachmentofthesetumorstotheheart, itsrelationtoothersurrounding structures and the volume/mass of the tumor 85,89,94,95.
RECENT ADVANCES
Recently, as mentioned previously a TEE probe has been introduced that is capable of RT 3D imaging19. This 3DTEE transducer can provide conventional 2D images but is also capable of live RT 3D imaging. Initial experience with 3DTEE reveals its potential in complementing 2DTTE and 2DTEE especially in guiding surgical interventions on the mitral and aortic valves, the aorta, the LV outflow tract, and in congenital heart disease in addition to the visualization of mass lesions (Figure 8)19,96-99. Another much anticipated advance in the field is the development of 3D speckle tracking which holds the promise to provide a better assessment of LV function, strain, strain rate and dysynchrony than available technologies.
Figure 5. The evaluation of a left ventricular (LV) thrombus using 3DTTE. (A)
Four-chamber view showing no thrombus or aneurysm in the LV. (B)
Anterior-posterior cropping displays the large aneurysmcontaining thrombus
(arrow). (C, D) Sectioning of thrombus (C) and viewing it en face (D) shows
no evidence of lysis or liquefaction. RV = right ventricle. Reproduced with
permission from Duncan K, et al. Incremental value of live/real time threedimensional
transthoracic echocardiography in the assessment of left
ventricular thrombi. Echocardiography 2006;23(1):68-72.
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Figure 6. 3DTTE assessment of a left atrial myxoma. (A) Arrowhead points to a large echolucency consistent with a large hemorrhage. (B) Resected specimen
showing a large hemorrhage which corresponds closely to the echolucent area seen on 3DTTE. LA = left atrium; LV = left ventricle; RA = right atrium;
RV = right ventricle. Reproduced with permission from Mehmood F, et al. Live three-dimensional transthoracic echocardiographic assessment of left atrial
tumors. Echocardiography 2005;22(2):137-143.
Figure 7. 3DTTE assessment of a left atrial hemangioma. (A) Arrowheads point to two of the large number of closely packed echolucencies in the tumor
mass with sparse solid tissue. (B) Resected specimen showing multiple vascular areas. LA = left atrium; LV = left ventricle; MV = mitral valve; RA = right
atrium; RV = right ventricle. Reproduced with permission from Mehmood F, et al. Live three-dimensional transthoracic echocardiographic assessment of
left atrial tumors. Echocardiography 2005;22(2):137-143.
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Figure 8. 3DTTE assessment of the mitral valve. (A,B) Mitral valve prolapse. Arrowhead in A points to prominent prolapse of A2 segment into left atrium (LA). Arrow in B points to a flail segment of the mitral leaflet with a torn chorda attached to it. (C) In another patient note the extensive prolapse of P1 scallop of the posterior mitral leaflet when the mitral valve was cropped from the atrial aspect to create an en face view. The other two scallops of posterior mitral leaflet (P2 and P3) and the three segments of anterior mitral leaflet (A1, A2, and A3) show less extensive prolapse. (D,E) Mitral annular abscess. Arrowhead in (D) points to the rugged surface of the abscess cavity (arrow) located laterally. In (E), abscess cavity is viewed en face by cropping from bottom. (F,G) Left atrial appendage. Arrow in (F) points to echodensity possibly a thrombus in left atrial appendage (LAA). Cropping of LAA using short axis cuts revealed the echodensity to be part of pectinate musculature (arrow in G). (H) Mitral valve ring viewed en face by cropping from the atrial aspect. Arrow points to en face view of Duran ring. (I) Mitral valve prosthesis. St Jude’s mitral prosthesis (MVR) viewed in open position from the atrial aspect. AO = aorta; AML = anterior mitral leaflet; LV = left ventricle; MV = mitral valve. Reproduced with permission from Pothineni KR, et al. Initial experience with live/real time three-dimensional transesophageal echocardiography. Echocardiography 2007;24(10):1099-1104.
 
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CONCLUSIONS
In the current era, the advancement of technology has allowed for the development of RT 3DTTE with proven incremental value on top of 2DTTE, and in some cases 2DTEE, for multiple indications which will continue to grow as more experience is gained through ongoing studies. This relatively new imaging modality has all the credentials to revolutionize the use of echocardiography once again.
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