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Four-Dimensional B-Mode and Color Doppler Echocardiography of the Human Fetus

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Introduction

Sonographic imaging of the fetal heart remains tech- nically challenging because of the complexities of fe- tal cardiac structure and function, the dependence of the acoustic access on fetal position and fetal move- ment. The technique is highly dependent on the oper- ator's skill, requires intense training, and has a steep learning curve. While performing two-dimensional (2D) echocardiography, the operator conceptually re- creates the spatial three-dimensional (3D) reality of the fetal heart out of the 2D sonographic images.

Although this approach continues to function well, the advantages of four-dimensional (4D) echocardiog- raphy, which is 3D imaging in real time, are poten- tially immense. Three-dimensional images can be cre- ated by postprocessing of the digital graphic informa- tion generated by sequential 2D imaging; however, when 3D imaging is performed in real time it consti- tutes 4D imaging. For echocardiography this trans- lates into instantaneous display of the spatial and temporal reality of the heart as the operator performs the scanning. Although the potential of 3D or 4D echocardiography has been appreciated for more than two decades, the actual development of this modality has to overcome significant engineering and compu- tational challenges. Not surprisingly, the early 3D methods did not possess the capability of imaging the fetal heart in real time with acceptable temporal or spatial resolution; however, recent remarkable technological breakthroughs have led to the commer- cial introduction of true 4D echocardiography instru- mentation in adult and pediatric cardiology and have raised the prospect of extending these newer tech- niques for fetal cardiac assessment. This chapter briefly reviews these recent developments in this field with emphasis on the Doppler mode.

History of Four-Dimensional Echocardiography

The origins of 3D medical imaging can be traced back three decades with the advances of computed tomography and magnetic resonance imaging. Essen-

tially, the tomographic image slices generated by these modalities are digitally reconstructed to pro- duce 3D images. These developments have revolution- ized medical imaging and diagnostics. Even with the continuing advances in technology, these modalities, however, cannot match the versatility of ultrasound for imaging the heart. The development of 3D echo- cardiography began in the 1970s and 1980s. Pioneer- ing groups of investigators, including Dekker and as- sociates [1], Ghosh and colleagues [2], and others [3], utilized various experimental approaches, which essentially consisted of offline reconstruction of 2D images. Subsequent research and development even- tually led to the clinical introduction of systems that utilized offline 3D reconstruction from multiplanar 2D images obtained via transthoracic or transesopha- geal routes by a rotational method or parallel scan- ning [4]. A recent remarkable technological accom- plishment in this field was the development of matrix phased array which allowed true real-time 4D imag- ing, introduced first by von Ramm and associates [5]

and is discussed later in this chapter.

Regarding the feasibility of 3D fetal echocardiogra- phy, initial investigations mostly consisted of 3D re- construction of sequential 2D images acquired either by free hand scanning combined with position sen- sors, or by motorized scanning with a one-dimen- sional linear-transducer array [6]. These approaches did not perform strictly 4D imaging and some form of cardiac gating was necessary to make any sense of the images. Another approach used two ultrasound devices concurrently with one generating 2D gray- scale and color Doppler images with 3D spatial move- ment tracking, whereas the other used umbilical arte- rial Doppler velocimetry to provide cardiac gating [7]. These laudable pioneering efforts depended on substantial postprocessing to generate the volume data set, were often cumbersome, and suffered from many limitations including poor spatial and temporal resolution.

Subsequent advances have addressed many of these limitations leading to the development of the two dis- tinct current systems; one is based on the recently in- troduced second-generation matrix 2D phased-array system and represents a significant breakthrough in

Four-Dimensional B-Mode

and Color Doppler Echocardiography of the Human Fetus

Dev Maulik

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nography: image acquisition; image processing; and im- age display. Real-time implementation of these sequen- tial processes constitutes 4D sonography (Fig. 34.1).

Three-dimensional images are acquired either by direct scanning with 3D ultrasound beam produced by 2D matrix array transducers or reconstructed from a series of 2D ultrasound images as discussed in the previous section. Color Doppler interrogation which is based on mean Doppler angular frequency shift can be performed in both these approaches;

however, the inherent limitations of Doppler sonogra- phy, such as angle dependence, are valid in these mo- dalities. Power Doppler can be used without this lim- itation; however, the loss of flow directional informa- tion significantly restricts the utility of this approach.

Three-dimensional color Doppler flow depiction can be used to quantify abnormal flow conditions such as regurgitant jets. Potential also exists to quantify volu- metric flow. Many of these functions can be per- formed now to a variable degree with dedicated off- line processing. Future technological advances may permit real-time hemodynamic assessments, includ- ing flow quantification, with greater reliability than has been possible up to now.

Three-dimensional image processing requires de- fining the spatial location of a point in 3D space from the digital graphic information. The unit of 3D spa-

tial graphic information is known as a voxel. The term stands for volume pixel and constitutes the smallest definable unit of a 3D image. A voxel is the 3D counterpart of a pixel which defines location in a 2D plane. Geometrically, the relative spatial locations of a voxel are represented by the Cartesian co-ordi- nates x, y, and z (Fig. 34.2). The location is defined by the point's distances from three orthogonal planes determined by these co-ordinates. This is a funda- mental concept that is crucial for 3D ultrasound im- age processing and interpretation. Each voxel can be digitally quantified to represent objective properties such as opacity, density, color, velocity, or even time.

The ability to modify the opacity of a voxel is critical for 3D imaging. This is known as opacity transforma- tion which allows visualization of internal morphol- ogy of an image which would otherwise be obscured by more opaque surface voxels.

Three-dimensional images can be displayed by (a) surface rendering with identification of various struc- tures, (b) multiplanar reconstruction with dynamic orthogonal display, or (c) as a texture mapped block, such as a pyramidal 3D object, which can be rotated and cropped to reveal internal structures or flow.

Reconstructed 3D images are subject to motion arti- facts which may be generated by fetal movements, pa- tient movements including breathing, or inadvertent transducer movement; however, direct 3D imaging em- ploying the 2D matrix transducers is not subject to similar motion artifacts except when two or more images are combined to produce a wide angle view.

Two-Dimensional Matrix Array

The 2D matrix array technology essentially consists of a phased-array transducer with 3,000 piezoelectric elements all of which transmit and receive ultrasound (Fig. 34.3; Sonos 7500 with X4 transducer, Philips Medical Systems, Andover, Mass.). The enormous vol- Fig. 34.1. Steps of four-dimensional sonography. 3D three

dimensional, 4D four dimensional

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ume of data thus generated offer a formidable chal- lenge in real-time processing; however, the system re- solves this issue by devising a highly innovative tech- nological solution known as subarray beam forming (Fig. 34.4). The elements are connected via layers of wiring to several custom integrated circuits. The cur- rently marketed device uses many such circuits which are located in the handle of the transducer which it- self still remains very modest in size. These circuits perform the initial processing of the ultrasound sig- nals which are then transmitted to the main computer system of the device where further fast processing re- sults in the real-time on-line generation of moving cardiac images. The system allows color Doppler flow depiction in real time in conjunction with the 4D de- piction of cardiac anatomy.

The system generates a 3D pyramid-shaped volu- metric sector restricted to an angle of about 308±508 (Fig. 34.5). No gating is needed for this volume. A wider pyramidal sector image measuring 90´908 can also be produced. This is accomplished by swift auto- matic acquisition and integration of four sectors in real time during consecutive cardiac cycles with each sector measuring approximately 23´908; however, generation of the extended sector requires some form of cardiac gating which in the adult or pediatric patient is pro- vided by a modified type of electrocardiographic trig- ger. Although this is not feasible to accomplish in the fetus, an external electronic periodic trigger, which Fig. 34.3. Microscopic view of a matrix array transducer. Each

small square is an active ultrasound element. The size of a human hair is shown for comparison (arrows). (From [9])

Fig. 34.4. Graphic depiction of the concept of subarray beam forming

Fig. 34.5. Two-dimensional matrix ar- ray: the sector size. a On-line 3D scan- ning. The sector size depends on cho- sen image resolution or line density, and is about 30´508. b Wide-angle scanning. An arrow sector is scanned during each of four consecutive heart beats. The four sectors (shown with dif- ferent color coding) are integrated automatically within a fraction of sec- ond. (From [9])

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can approximate the fetal heart rate, has been used suc- cessfully to produce a reliable full volume data set of the fetal heart (Fig. 34.6) [12].

Brightness and contrast can be adjusted to opti- mize the 3D image quality. The images can be cropped using the Cartesian co-ordinate x, y, and z planes as well as oblique planes to obtain the 3D per- spective.

Two-Dimensional Matrix Array:

Fetal Application of the Technique

The utility of the new system has been shown in adult patients for imaging the coronary arteries and for evaluating mitral stenosis [10, 11]. Preliminary experience in fetal cardiac assessment shows that this technology can provide a comprehensive assessment of cardiac valves, chambers, both atrial and ventricu- lar septal walls, and great vessels [12]. Moreover, un- like real-time 2D echocardiography, both the atrial and the ventricular septal walls as well as the cardiac valves can be visualized as if the examiner is directly facing these structural surfaces in three dimensions in real time (also known as en face view) for any ab- normalities (Fig. 34.7). Three-dimensional color Dop- pler allows comprehensive assessment of regurgitant and shunt lesions (Figs. 34.8, 34.9). In normal fetuses, the foramen ovale with right-to-left physiological shunting can be well visualized by 4D color Doppler (Fig. 34.8). In a 36-week-old fetus with complete at-

rioventricular septal defect, we could fully visualize the septal defect from any desired angulation includ- ing en face views (Figs. 34.10, 34.11). Four-dimen- sional color Doppler allowed depiction of abnormal hemodynamics of the lesion with clarity (Fig. 34.12).

Such comprehensive assessment is not possible using real-time 2D echocardiography because of its inabil- ity to view the defect using cross sections taken at different levels and angulations.

Fig. 34.6. Two-dimensional matrix array: the sector size.

Pyramid-shaped wide-angle sector image of the fetal heart.

Fetal back is toward the apex of the pyramid. Fetal spine can be seen at the right upper corner of the apex. The ar- rowhead points to the foramen ovale. RA right atrium, LA left atrium, RV right ventricle, LV left ventricle. (From [12])

Fig. 34.7. Four-dimensional echocardiography in a fetus with complete atrioventricular septal defect. En face view of the defect (asterisk) from the inferior aspect. S ventricu- lar septum. (From [12])

Fig. 34.8. Four-dimensional echocardiography in a normal 31-week-old fetus. Color Doppler image shows physiologi- cal right-to-left shunting (arrowhead). RA right atrium, LA left atrium, RV right ventricle, LV left ventricle, IVC inferior vena cava. (From [12])

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One of the apparent limitations of the technique in our preliminary assessment is the inability to use fetal electrocardiography signals to trigger the volume ac- quisition which is the approach utilized in assessing the adult heart; however, as mentioned above, a simu- lated heart rate can be used within the range of the nor- mal fetal heart rate with no visually detectable artifacts.

The other potential challenge in any fetal imaging is re- lated to fetal movements which may also interfere with live 3D imaging; however, this is not a significant prob- lem in this system because of the very fast volume ac- quisition in both B- and color Doppler modes.

Motorized Curved Linear-Array System and Spatio-Temporal Image Correlation

This is an advanced system essentially based on 3D im- age reconstruction from sequentially acquired 2D images (Voluson 730 Expert System, General Electric Medical Systems, Kretztechnik, Zipf, Austria). The transducer assembly encases a curved linear array of transducer elements and a motor drive. The drive mech- anism allows an automated sweep of the target area to generate 2D images sequentially constituting the vol- ume data set. This method is inherently inadequate for fetal echocardiography because of fetal cardiac mo- tion. Development of the spatio-temporal correlation technology (STIC), however, has resolved this issue.

An integral part of the 3D volume acquisition sys- tem, STIC processing, determines the fetal heart rate

from the systolic peaks of the fetal cardiac motion and immediately reorganizes the 2D images with spa- tial and temporal coherence so that images from the same cardiac cycle are collated together to form a single volume data set for that cardiac cycle (Fig. 34.13). Many such volumes are produced during a single sweep, and the actual number depends on the duration of the sweep and the heart rate. The images can be displayed as orthogonal multiplanar, volume-rendered, or single-plane displays either as cine loops or still images. The images can be gray scale or color B mode, color Doppler, or a combina- tion of B mode and color Doppler with variable translucency, the so-called glass-body display. The Fig. 34.9. Four-dimensional echocardiography in a fetus

with complete atrioventricular septal defect. The pyramidal section has been cropped to show regurgitation (R) from the right-sided component of V. AO aortic cross section.

(From [12])

Fig. 34.10. Four-dimensional echocardiography in a fetus with complete atrioventricular septal defect. a Two-dimen- sional B-mode image of the lesion. The upper horizontal ar- row shows the ventricular septal defect; the lower horizon- tal arrow shows the absence of the atrial septum. b Four- chamber view cropped to show the common atrioventricu- lar valve (V) and the defect (asterisks). RA right atrium, LA left atrium, RV right ventricle, LV left ventricle. (From [12])

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STIC processing is very fast so that the images are produced in real time. Moreover, B-mode resolution has continued to improve. The 3D image volume data set can be archived and reexamined comprehensively later which may improve the efficacy of the prenatal diagnosis of congenital heart defects.

The STIC approach is sensitive to movements. Fe- tal body movements, or sometimes even fetal breath- ing, will produce artifacts rendering the images unin- terpretable. Maternal breathing or transducer move- ment may also create this problem.

Fetal Echocardiography with STIC Technology

Introduction of this technique represents a significant advance in prenatal cardiac diagnosis. Several investi- gators have reported the use of this approach for fetal echocardiography [13±15]. These studies demonstrate the feasibility of using the STIC approach to obtain not only the traditional views of the fetal cardiac anatomy but also the ability to view the cardiac structures in an innovative manner. Our own prelim- inary experience corroborates these reports. A single sweep was able to produce four-chamber and outflow tract images with the color Doppler demonstrating the cross-over relationship between the pulmonary and the aortic outflows (Figs. 34.14, 34.15). It is ap- parent that this approach and its future evolution Fig. 34.12. Four-dimensional echocardiography in a fetus

with complete atrioventricular septal defect. Four-chamber view cropped to show the color Doppler depiction of shunt across the septal defect. RA right atrium, LA left atrium, RV right ventricle, LV left ventricle. (From [12])

Fig. 34.13. Raw data volume showing a beating fetal heart during a slow 3D sweep. This information is used to calcu- late the fetal heart rate. (From [8])

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could substantially increase the ease of fetal echocar- diography and improve its diagnostic efficacy.

Conclusion

Development of 4D ultrasound represents a major ad- vance in non-invasive diagnostic technology and its introduction in clinical practice has initiated a signif- icant paradigm shift in medical ultrasound imaging.

Four-dimensional echocardiography allows a more comprehensive assessment of the fetal cardiac anato- my and hemodynamics than has been achievable in any of the current or legacy systems. It has the real potential of significantly expanding the scope of in utero diagnosis of congenital heart diseases and other abnormalities of the fetal heart. This is a very new technology and there is a real dearth of investigations critically evaluating its promises and limitations in the fetal application. This is especially relevant for ex- tending its use outside the domain of experts and en- thusiasts. At present, traditional 2D B-mode and Doppler sonography will continue to be the standard of practice for fetal cardiac assessment with substan- tial supplemental assistance from the 4D echocardiog- raphy which, however, has the strong potential to be- come the mainstream approach in the future.

Fig. 34.14. Spatio-temporal im- age correlation 4D echocardio- graphy in the color Doppler mode. Multiplanar view of the fetal heart simultaneously showing four-chamber view and the outflow tracts. RA right atrium, LA left atrium, RV right ventricle, LV left ventricle, AO aortic cross section, PA pulmo- nary artery, SP fetal spine

Fig. 34.15. Spatio-temporal image correlation 4D echocar- diography in the color Doppler mode. Single-plane view of the fetal heart showing cross-over relationship of the great vessels and the outflow tracts. RV right ventricle, LV left ven- tricle, RVOT right ventricular outflow tract, LVOT left ventricu- lar outflow tract. The arrows depict directionality of the flow

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5. Ramm OT von, Smith SW, Pavy HG Jr (1991) High259 speed ultrasound volumetric imaging system. Part II.

Parallel processing and image display. IEEE Trans Ul- trason Ferroelec Ferq Contr 38:109±115

6. Downey DB, Fenster A, Williams JC (2000) Clinical utility of three dimensional ultrasound. Radiographics 20:559±571

7. Deng J, Sullivan ID, Yates R, Vogel M, McDonald D, Linney AD, Rodeck CH, Anderson RH (2002) Real-time three-dimensional fetal echocardiography: optimal imaging windows. Ultrasound Med Biol 28:1099±1105 8. Franke A, Kuhl HP (2003) Second generation real time

3D echocardiography: a revolutionary new technology.

Medicamundi. Philips Ultrasound 47:34±40; http://

www.medical.philips.com

phy of the human fetus. Echocardiography 20:715±721 13. Goncalves LF, Lee W, Chaiworapongsa T, Espinoza J,

Schoen ML, Falkensammer P, Treadwell M, Romero R (2003) Four-dimensional ultrasonography of the fetal heart with spatiotemporal image correlation. Am J Ob- stet Gynecol 189:1792±1802

14. DeVore GR, Polanco B, Sklansky MS, Platt LD (2004) The `spin' technique: a new method for examination of the fetal outflow tracts using three-dimensional ultra- sound. Ultrasound Obstet Gynecol 24:72±82

15. Chaoui R, Hoffmann J, Heling KS (2004) Three-dimen- sional (3D) and 4D color Doppler fetal echocardiog- raphy using spatio-temporal image correlation (STIC).

Ultrasound Obstet Gynecol 23:535±545

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