FETAL HEART ASSESSMENT USING THREE-DIMENSIONAL ULTRASOUND

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1 FETAL HEART ASSESSMENT USING THREE-DIMENSIONAL ULTRASOUND T.R. Nelson, Ph.D., M.S. Sklansky, M.D., D.H. Pretorius, M.D. 1 3 Divisions of Physics and Ultrasound, Department of Radiology 2 Division of Pediatric Cardiology, Department of Pediatrics Abstract University of California, San Diego, La Jolla, California, Cardiac anatomy is complex and often difficult to visualize or comprehend. 3D echocardiography is an area undergoing rapid development that represents a natural extension of conventional sonography methods which require integrating a series of 2D image slices to develop a 3D impression of underlying anatomy or pathology. This paper will review some of the basic concepts behind three-dimensional fetal echocardiography and describe some areas of clinical application. Among the many potential advantages of 3D fetal echocardiographic visualization compared to current real-time 2D ultrasound methods are improved visualization of normal and abnormal fetal cardiac structures, and evaluation of complex cardiac structures for which it is difficult to develop a 3D understanding. Reduced patient scanning times could increase the number of patients scanned, increasing operational efficiency and cost-effectiveness. Standardization of ultrasound examination protocols could lead to uniform examinations decreasing health care costs. Ultimately the improved understanding of cardiac anatomy and function afforded by 3D fetal echocardiography will make it easier for primary care physicians to understand complex cardiac anatomy. Introduction The complex anatomy and dynamics of the fetal heart make it a challenging organ to image. The fetal heart is particularly difficult because it is located deep within the mother s abdomen and direct access to elctrocardiographic information is difficult. Thus more complex imaging and analysis methods are necessary to obtain diagnostic information regarding fetal cardiac anatomy and function. Currently, the typical approach to overcome this problem is to scan repeatedly through the fetal heart to clarify the exact spatial relationships. With complex or abnormal cardiac structures this process can be time-consuming and tedious. Three-dimensional ultrasound (3DUS) methods that use advanced technology incorporating volume imaging methods including interactive manipulation of volume data using rendering, rotation and zooming in on localized features can greatly assist comprehension of complex fetal cardiac anatomy. Currently most fetal cardiac visualization is performed using graphics workstations to provide interactive performance. 3DUS imaging also provides the physician with the capability to evaluate the patient after they have left the scanning suite and re-evaluate the diagnosis with experts across networks at remote locations.

2 While early 3D echocardiographic efforts have focussed on the adult and pediatric patient (Pandian 1992), fetal cardiac imaging remains an important and challenging area (Crane et.al. 1994). Conventional 3DUS imaging equipment can produce static volume images of the heart which have shown some promise in imaging the great vessels, and relatively non-moving areas (Zosmer et.al. 1996) although critical areas of cardiac anatomy are generally poorly visualized due to motion (Mertz et.al. 1995) and small size (Meyer-Wittkopf et.al. 1996). Chang et.al. (1997) showed that accurate fetal heart volumes could be made with static imaging methods and demonstrated the fetal heart volume changes through gestation. Images of the fetal heart including each chamber throughout the cardiac cycle have been demonstrated using non-ecg motion Fourier analysis based gating (Nelson et.al. 1996). This work recently was extended by Sklansky et.al. (1997) to show that gated fetal heart images can demonstrate fetal cardiac anatomy more consistently than 2D methods and with less dependence on the orientation of the acquisition. It also is possible to produce gated cardiac images using M-mode (Deng et.al. 1996) and Doppler (Kwon et.al. 1996) methods to determine the fetal heart rate. Eventually, clinical 3DUS systems will provide the necessary memory, computational power and analysis tools to obtain high quality gated fetal cardiac images. 3D Fetal Echocardiography Volume Data Acquisition There are several approaches that have been used for fetal cardiac imaging. Most of these are derived from routine 2DUS methods. 2DUS methods have traditionally relied on both static and real-time imaging to understand fetal cardiac anatomy and function. Currently, commercial 3DUS systems provide the capability to produce non-gated, static images of the fetal heart. While these systems can provide valuable information regarding cardiac and great vessel anatomy, they have significant limitations regarding function assessment; in some cases the lack of gated images compromises clear delineation of intracardiac and vascular structures. Prototype research systems producing gated images of the fetal heart have demonstrated fetal cardiac anatomy more consistently than with static 3D methods. This section will provide a brief overview of methods that can be used to obtain non-gated and gated three-dimensional fetal echocardiographic data. Figure 1 block diagram of a three-dimensional ultrasound imaging system. Image data are collected in synchronization with position data and stored in a memory system. Subsequently, position and image data are combined to build a volume which is processed, rendered and displayed on the graphics display. The first step in acquisition of a volume data set is to obtain echo data from throughout the volume of interest. The general features of a volume sonographic data acquisition system are shown in Figure 1 and have been reviewed elsewhere (Nelson 1998).

3 3DUS Scanner Designs In general, current volume sonographic imaging systems are based on commercially available onedimensional or annular transducer arrays whose position is accurately monitored by a position sensing device. Position data acquisition approaches generally can be grouped into one of two types: systems with an integrated positioning system as part of the transducer assembly (Figure 2) and systems with an externally located positioning system (Figure 3). An advantage of an integrated positioning system is that the sonographer uses the transducer in the same manner as with conventional 2DUS systems and only has to immobilize the probe during the volume acquisition. These probes tend to be relatively larger than standard 2DUS probes and thus may be more cumbersome to use in clinical practice. Volumes can be acquired and reconstructed rapidly and without registration artifacts. The volume field-of-view is limited with these systems which but generally does not pose problems for the fetal heart and great vessels but may for other larger organs. External positioning systems require additional calibration steps to coordinate the transducer image and position data. As a result there is generally a brief delay between data acquisition and display with these systems. Such systems do offer the advantages of free-hand scanning over larger volumes and extended distances which can be advantageous in fetal, pediatric and adult patients. Figure 2Three-dimensional echocardiography acquisition method using an integrated position sensor/transducer assembly. During patient data acquisition a 2D slice is selected from the mid cardiac region and the automatic scan sequence started. Data are acquired directly into volume memory during 4-10 seconds and immediately displayed after the scan is completed. Figure 3 echocardiography acquisition method using an external electro-magnetic position sensor attached to the transducer. During patient data acquisition a free-hand scan is made over the maternal abdomen in approximately seconds using conventional ultrasound equipment and transducers with a position sensor attached. The scan is made slow enough to obtain images throughout the cardiac cycle at each location and fast enough to complete the scan without fetal motion. While there are a variety of position sensing devices used with external positioning systems including mechanical translation stages (linear or rotational), articulated arms, electro-magnetic (EM) field transmitter/receivers, acoustic methods using spark gaps and microphones, optical methods based on light emitting diodes (LED s) and laser rangerfinders (Detmer et.al. 1994, Hernandez et.al. 1996, 1996a, King et.al. 1990, Kossoff et.al. 1995a, Moskalik et.al. 1995, Nelson et.a. 1992, Raab et.al. 1979), electro-magnetic position sensing has been the most widely used. Advantages of EM methods include (1) their small size (<1.0 cm) allowing them to be easily mounted on the transducer, and (2) reasonably good accuracy although they may suffer from susceptibility artifacts that distort the local EM field producing positional inaccuracies.

4 Regardless of what approach is used, a position location accuracy of less than 1 mm and angular accuracy of less than 0.5 degrees is necessary to obtain sufficient accuracy for volume reconstruction; something quite achievable depending on the care employed in calibration and setup. Since many clinical scanners provide sub-millimeter resolution, with higher imaging frequencies, and improved spatial resolution, further improvements or alternate methods of position location will become necessary to produce high quality volume data. Recent work with image correlation methods offers promise to reduce the need for external position sensing devices. Acquiring Fetal Cardiac Volume Data Once the transducer and positioning system are coordinated, data acquisition is essentially the same as with conventional real-time scanning. The sonographer makes a sweep over the patient area of interest acquiring slice data into the scanner or an external workstation. Integrated systems acquire image data directly into volume memory while attached position systems typically acquire image data via a video digitizer link rather than direct digital data. Eventually, digital data will be acquired directly with scaling information which will greatly improve the quality of volume data. Systems that add position sensing to commercially available systems require a calibration process at the initial setup in order to obtain quantitative data from the images. Incorporation of scaling data is necessary to permit subsequent measurement of distance, area and volume in the data volume. After serial 2DUS images comprising a volume are acquired, a volume is created by placing each image at the proper location in the volume. This process may occur concurrently with scan image acquisition as in integrated systems. Systems that acquire each image using a free hand imaging technique must re-register each slice to the volume through a series of trigonometric calculations. Since the fetus is indirectly imaged with the methods described here and is not subject to external control the possiblity of fetal body motion is significant. Volume data acquired during times of fetal motion generally has compromised diagnostic value and is best discarded. Since most fetal cardiac data can be acquired in less than 20 seconds it is possible to quickly re-acquire a new volume after the motion has stopped. Volume acquisitions performed in standard orientations, such as transverse and longitudinal projection generally provide higher quality volume data that those acquired obliquely. Once acquired, fetal cardiac data volumes may require 50 to 100 Mbytes of storage depending on the duration of the acquisition and the number of images per second that are acquired. For example a fetal cardiac examination may require seconds of data at 30 frames/second and volumes may range from 2-16 Mbytes for ungated data to Mbytes for gated data. Physiologic Synchronization Imaging cardiac dynamics or blood flow as a function of time in the cardiac cycle requires some method to synchronize the data to the appropriate time of the cardiac cycle. For adult and pediatric cardiac imaging the electrocardiogram (ECG) signal from patient electrodes provides a trigger signal to synchronize with the data acquisition; in the fetus such methods are much more difficult. An alternate approach is to perform some type of analysis on the acquired data to extract information about the motion in the image field; such as due to the periodic contraction of the heart. Nelson

5 et.al. (1995, 1996) used temporal Fourier analysis of the cardiac motion to identify the fundamental frequency of the heart motion and then used the phase information from the Fourier transform to identify the location of each beat within the acquired images (Figure 4). This method does not require electrical connection to the patient and utilizes the acquired data to determine periodic behavior; it is a retrospective method compared to real-time during the acquisition. Other approaches use M-mode (Deng, 1996) and Doppler (Kwon, 1996) methods to determine the heart rate. In general, synchronization of images to physiologic triggers is demanding from a data storage, analysis and display point of view and is not widely available at this time. Fetal Cardiac Data Visualization Figure 4 method of determining the cardiac cycle timing using temporal Fourier analysis of the periodic cardiac motion. (A) A region-of-interest (ROI) is positioned over the fetal heart. (B) the magnitude display of the temporal Fourier transform, (C ) the cumulative amplitude spectrum of the temporal Fourier transform showing the location of the fundamental cardiac beat frequency and (D) a time slice through the 2DUS acquisition in the region of the heart showing the heart motion with the Fourier based cardiac cycle synchronization shown as vertical lines corresponding to end-diastole. The challenge in 3D echocardiography is to make available to the physician the capability to completely understand cardiac anatomy and function. There are basically four basic aspects to consider to optimize 3D echocardiography visualization (Nelson, 1993): (1) standardization of display by rotating the heart into easily recognizable orientation with appropriate landmarks (e.g. spine, sternum, etc.), (2) using slice projections in arbitrary orientations to optimize anatomic visualization showing images similar to 2DUS, (3) using volume rendering which includes ray-casting and allows evaluation of the blood pool, and (4) using animation to help visualize and evaluate the dynamics of cardiac function. Extraction of a planar image of arbitrary orientation at a particular location in a three-dimensional data set requires minimal processing and offers the physician interactive display of planar slices through the heart. Retrospective evaluation of fetal cardiac anatomy can be performed, particularly viewing of planes perpendicular to the primary exam axis and other orientations not possible during data acquisition (Figure 5). Multiple slices displayed simultaneously can be particularly Figure 5 Three orthogonal slices through the volume for a gated acquisition. The upper left view shows one frame of the 2DUS acquisition. The other three planes are from one volume of the gated reconstruction showing orthogonal intersecting slices that demonstrate standard cardiac views. The cross indicates the point of common intersection

6 valuable to assist in understanding fetal cardiac anatomy. Typically, slicing methods should be fully interactive, replicating the scanner operational "feel". Multi-plane displays are often combined with rendered images to assist in localization of slice plane position. Volume rendering methods are used to display the chamber, valve and great vessel data from the blood pool. Typically, volume rendering methods are used to display the chambers and great vessels with planar slicing methods used to display grey-scale data. Animation sequences such as rotation and gated "cine-loop" review are used to assist understanding cardiac anatomy and function. Without animation, the physician often has a difficult time extracting three-dimensional information from two-dimensional displays. Typically, motion can be viewed at normal, accelerated or reduced speed to enhance comprehension. Furthermore, analysis of dynamic function has the potential to increase the diagnostic value of many studies (Schwartz et.al. 1994, Sklansky 1998). In some cases image quality can further be improved by filtering the volume data with either 3D median and Gaussian filters prior to application of visualization algorithms (Pratt, 1991, Russ, 1989). More specialized analysis of the chambers and blood pool can be obtained by using algorithms that identify the lower signal intensity of blood compared to myocardial tissue to extract the chambers and vessels using methods similar to thresholding. The isolated volume data containing signals from the blood can be volume rendered to show chambers and great vessels in a single image (Figure 6). This approach has been used used to analyze cardiac function and measure chamber volume, stroke volume, and ejection fraction. Figure 6 Imaging of the fetal heart chambers showing volume rendered images of the cardiac chambers and vessels. The signal void in the original acquisition has been extracted to show only the blood signal. Chamber and vessel rendering uses a modified maximum intensity method with depth-coding Quantitative Measurements An important part of cardiac imaging is to provide data of sufficient quality to measure the length, area or volume of chambers and vessels and follow temporal changes. While visual assessment is valuable, quantitative data provides a more accurate basis for decision making and comparison against previous studies or reference data bases. 3DUS data are ideally suited to volume measurement and good results have been reported (Nelson et.al. 1993a, Riccabona et.al. 1995, 1996). Volume measurement is accomplished by masking using either individual plane masks or a volume interactive tool to limit the volume region-of-interest to only the object of interest. After the object is masked the voxels are summed and the matrix voxel scaling factors applied to determine the volume. This approach permits measurement of volume for regular, irregular and disconnected objects with an accuracy of better than 5% for regular and irregular objects and in-vivo organs relatively independently of the object size over several orders of magnitude. In general, the improved measurement accuracy afforded by volume sonographic methods makes possible accurate quantitative measurement of heart chambers, vessel dimensions and organ volumes. Chang et.al. (1996) have shown that accurate measurements of fetal heart volume can be made with non-gated 3DUS methods. The volume of small fetal cardiac chambers and structures (<1 ml) can be measured throughout the

7 cardiac cycle with gated methods (Figure 7); preliminary results have been encouraging. Clinical Findings Three-dimensional fetal echocardiography has shown the capability to improve fetal cardiac diagnosis by using reformatted planar sections, volume rendered chamber images and by using volume rendered cut planes to portray a "surgeon's eye view of the heart. Meyer-Wittkopf et. al. (1996) found that studying cadaveric specimens of fetal hearts with CHD nongated methods could generate planar reconstructed images of intracardiac anatomy with high resolution. In utero, 3D fetal Figure 7 Measurement of fetal cardiac chamber volumes for each chamber throughout the cardiac cycle echocardiography however, is limited by suboptimal 2D imaging, random fetal motion, and fetal cardiac activity which can significantly limit identification of fetal cardiac anatomy and detection of small defects. Nongated 3D fetal echocardiography generates a single volume that mixes together data from all parts of the cardiac cycle (Figure 8). As a result, nongated displays cannot reconstruct cardiac motion, and may be expected to have suboptimal accuracy and resolution. Mertz et. al. (1995) studied fetuses using nongated 3D fetal echocardiography with reformatted, planar displays. They showed in fetuses with CHD that nongated fetal 3D echocardiography was disadvantageous compared with 2D imaging because of Figure 8 series of volume rendered images at end-diastole and end-systole in the cardiac cycle. Note the tricuspid valve (TV) which is clearly seen in each image. The TV is closed in ventricular systole and open during ventricular diastole. Interactive display of cardiac dynamics greatly assists comprehension of cardiac anatomy and function. various movement artifacts. Similar findings were found by Leventhal et.al. (1998) and Pretorius et.al. (1997) where nongated 3D fetal echocardiography was disadvantageous compared with 2D imaging in terms of demonstrating normal and abnormal fetal cardiac anatomy. They also identified several cases of false positives (left atrial mass, ventricular septal defect, thickened mitral valve, and pericardial effusion) using nongated imaging. An important factor in their study was the relative skill level of the interpreter and the importance of animation in deriving cues regarding cardiac anatomy. Chang et.al. (1997) concluded that 2D imaging was still the preferred approach for quantitative assessement of fetal heart volumes because of technical challenges to 3D imaging and reconstruction.

8 In contrast, Zosmer et. al. (1997) reported that nongated 3D fetal echocardiography can generate good quality reconstructed planar images in some fetuses, although only when real-time scanning included a four-chamber view with the ventricular septum parallel with the ultrasound beam. Sklansky et.al. (1998) compared gated with nongated data sets where each series was condensed to a single volume, so that each 2D sweep could be compared with its respective gated and nongated volume data sets (Figure 9). Their work showed that conventional 2D imaging could provide a fairly complete evaluation of the fetal heart when real-time scanning includes the four-chamber view with a sweep across the outflow tracts. They also showed that nongated 3D fetal echocardiography allowed visualization of some structures and views not demonstrated with 2D ultrasound, particularly when the 2D acquisition does not include a four-chamber view. Their principal new finding showed that gated 3D fetal echocardiography provided significantly better visualization and comprehension of cardiac anatomy than nongated 3D fetal echocardiography (Figure 10). The superiority of gated 3D fetal echocardiography compared to nongated 3D fetal echocardiography derives from improved image quality due to lack of motion related blurring and the added anatomic clues are derived from viewing cardiac motion. Figure 9 orthogonal slices through the volume for a gated acquisition. The upper left view shows one frame of the 2DUS acquisition. The other three planes are from one volume of the gated reconstruction showing orthogonal intersecting slices that demonstrate standard cardiac views. The cross indicates the point of common intersection. Figure 10 graph showing the superior ability of gated 3D echocardiographic methods to identify key cardiac structures. The gated 3D echocardiographic data is able to visualize the same structures as the original 2DUS acquisition plus additional structures not visible in the 4 chamber view. The non-gated data is noticibly poorer than the gated data (adapted from Sklansky et.al. 1998). Gated studies can display animated orthogonal reformatted planar displays, volume rendered cut planes, and surface renderings of the entire heart or blood pool further enhancing comprehension (Figure 11) (Nelson 1996, Sklansky 1997, Deng 1996). The prototype gated fetal 3DE system described by Deng et al utilizes manual gating and a relatively slow sampling rate (Deng 1996), both of which limit that system's potential for clinical application. Sklansky et.al. (1997) showed, using a prototype gated fetal 3DE system with automated gating and an acquisition rate of 30 frames per second, the advantages of using gated 3D fetal echocardiography to reconstruct and display specific cardiac structures not visualized with 2D imaging.

9 While the potential advantages of 3D fetal echocardiography over conventional 2D echocardiography seem apparent, several challenges have limited the extension of 3D fetal echocardiography to the prenatal diagnosis of CHD. To begin with, three-dimensional reconstruction relies on superb 2D image quality. Fetal 2D quality, typically inferior to that of pediatric transthoracic echocardiography, and usually far inferior to transesophageal imaging, limits all strategies for three-dimensional reconstruction. Moreover, fetal cardiac imaging typically requires small, unpredictable, and changing transabdominal windows, which technically limits the ways in which 2D data may be acquired for three dimensional reconstruction. Random fetal movement and breathing, which cannot be controlled clinically, degrade the Figure 11 A series of volume rendered images at enddiastole and end-systole in the cardiac cycle. Note the tricuspid valve (TV) which is clearly seen in each image. The TV is closed in ventricular systole and open during ventricular diastole. Interactive display of cardiac dynamics greatly assists comprehension of cardiac anatomy and function resolution of reconstructed volume data. Unlike three-dimensional reconstruction of static structures, 3D fetal echocardiography reconstructs an image or images of a beating heart, with or without the dimension of time. Thus, an additional challenge unique to fetal cardiac imaging has been the lack of a readily available means to gate the acquired 2D image data to their respective points in the cardiac cycle except under research uses. Finally, the small size of the fetal heart at weeks, together with its rapid rate of contraction (approximately beats/minute), pushes to the limit the current spatial and temporal resolution of three-dimensional imaging and reconstruction methods. Optimization of 3DUS Data Visualization Optimization of 3D fetal echocardiographic techniques requires that gating strategies and image processing algorithms need to continue to evolve in an effort to maximize image resolution and to minimize algorithm-related error. With time, processing and display algorithms will become faster, more automated, and less laborious. The time-consuming process of slicing and rotating planar and rendered displays to achieve optimal displays will improve with increasing experience. Quantitative determinations of volume and function will become more accurate, reproducible and rapid as algorithms for automatic endocardial boundary tracing evolve. Finally, although current display modalities portray the illusion of three dimensions with rendered images, display modalities in the future may provide more rapid or even on-line three dimensional reconstructions, and displays may ultimately become truly three-dimensional in real time. For the moment determination of the optimal method for display of fetal echocardiographic data remains challenging requiring continuing development, since each choice of visualization method offers trade-offs. Viewing planar slices from arbitrary orientations is a straightforward method of display for interactive review. It most closely resembles clinical scanning procedures. Additionally, planar slices extracted from volume data offer projections that may not be available during patient scanning. Slice displays do not necessarily require intermediate processing or filtering of ultrasound

10 image data, which further minimizes delay time to viewing. Volume rendering methods, on the other hand, produce high-quality images that are relatively tolerant of noise in the ultrasound data with filtering improving results as long as it does not obscure fine detail. Careful selection of opacity values helps provide an accurate rendition of the structure being studied and can be particularly valuable for complicated anatomic structures. Transparency permits viewing surface and subsurface features, which can help in establishing spatial relationships. Stereoscopic viewing enhances identification of small structures with greater confidence in less time. Physician involvement in optimizing and enhancing visualization tools is essential as part of the ongoing evaluation of cardiac visualization techniques. Regardless of which viewing technique is used, a key benefit of 3DUS is that once the patient has been scanned, the original data may be analyzed for the entire region or magnified sub-regions without the need to rescan the patient. Summary 3D fetal echocardiography is an area undergoing rapid development that represents a natural extension of conventional sonography methods which require integrating a series of 2D image slices to develop a 3D impression of underlying anatomy or pathology. Interactive volume visualization enhances the diagnostic process by providing better delineation of complex anatomy and pathology. However, the interactivity essential to assist physicians comprehend patient anatomy and injury and quickly extract vital information currently requires affordable high performance computer graphics systems which are now beginning to become available. Interactive manipulation of cardiac images by rotation and zooming in on localized features or isolating cross-sectional slices greatly assists interpretation by physicians and allows for quantitative measurement of cardiac volumes. Among the many potential advantages of 3D fetal echocardiography visualization compared to current real-time ultrasound methods are improved visualization of normal and abnormal cardiac structures, and evaluation of complex cardiac structures for which it is difficult to develop a 3D understanding. Reduced patient scanning times compared to current 2D techniques could increase the number of patients scanned, thereby increasing operational efficiency and make more costeffective use of sonographers and equipment. Standardization of the ultrasound examination protocols can lead to uniformly high-quality examinations and decreased health care costs. Ultimately an improved understanding of fetal cardiac anatomy and function afforded by 3D fetal echocardiography will make it easier for primary care physicians to understand complex cardiac anatomy. Tertiary care physicians specializing in ultrasound can further enhance the quality of patient care by using high-speed computer networks to review 3D fetal echocardiography data at specialization centers. Access to volume data and expertise at specialization centers affords more sophisticated analysis and review, further augmenting patient diagnosis and treatment.

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