Three-dimensional ultrasonography (3DUS) can be combined with conventional two-dimensional ultrasonography (2DUS) for the evaluation of normal and abnormal fetal anatomy. Development of cost-effective high-performance computers and sophisticated image analysis software now makes it practical for 3DUS to be conveniently integrated with standard diagnostic imaging equipment. The previous chapter summarized basic concepts regarding the acquisition and fundamental concepts of ultrasound volume data. This overview will describe how this information can be applied to specific problems during pregnancy.
Although 3DUS applications have been described for over two decades, one of our initial challenges was to evaluate their clinical value against a backdrop of emerging technology. In 2005, a literature review of more than 500 related articles suggested that additional diagnostic information was particularly useful for facial anomalies, neural tube defects, brain anomalies, and skeletal malformations.1 Other potential benefits involved early pregnancy evaluation, nuchal translucency (NT) measurements, weight estimation, fetal lung volumetry, growth evaluation, and possibly maternal–fetal bonding. Technical developments, such as spatiotemporal image correlation (STIC) algorithms, were also cited for improving our ability to examine rapid changes in the fetal heart. Chapter 47 will more closely examine the emerging field of four-dimensional ultrasonography (4DUS).
We have witnessed an impressive refinement of image analysis tools and their migration from dedicated image workstations to notebook computers. This technology permits the examiner to choose among many different visualization techniques with a variety of output display modes as summarized in Chapter 47. In most cases, volume sonography can be generally considered as an important diagnostic technique that is complementary to conventional 2D imaging. Before specific examples of how 3DUS can be applied to pregnant women are reviewed, we will first describe a few general concepts for how 3DUS can be best applied during pregnancy.
Health care professionals are classically trained to translate 2D images into volume reconstructions for an improved understanding of spatial relationships and image patterns that suggest congenital abnormalities. Volume sonography provides the examiner with an opportunity to systematically evaluate anatomic structures with less interobserver dependency, sometimes in ways that are not possible through conventional 2D methods. A preliminary 2D sonographic scan for suspected fetal abnormalities can be very useful, and the results can be used to guide the subsequent 3D study. Once an initial differential diagnosis has been generated, the examiner should be able to formulate pending questions about the initial diagnostic impression that may or may not be satisfactorily addressed using 3DUS. If spina bifida is detected, for example, there may be a need to more precisely define the anatomic level of the defect. This information would help the clinician to estimate the risk of problems related to ambulation and bowel or bladder function.
In order to better understand the contribution of conventional imaging to 3DUS, Gonçalves et al2 compared both modalities in a blinded manner for 99 fetuses at a mean menstrual age of 24.4 ± 6.5 weeks. Complete agreement between 2DUS and 3DUS was observed for 90.4% of the findings. Six anomalies were missed by volume sonography, including ventricular septal defects (n = 2), interrupted inferior vena cava with azygous continuation (n = 1), tetralogy of Fallot (n = 1), and cystic adenomatoid malformation (n = 1). There were 12 discordant diagnoses between 2DUS and 3DUS. When compared to postnatal diagnoses (n = 106), the sensitivity and specificity of volume sonography was 92.2% and 76.4%, respectively. However, no significant differences in the diagnostic conformity to neonatal outcomes were found when the 3DUS results were compared to the sensitivity (96.1%) and specificity (72.7%) from 2DUS (P = .23). This study concluded that the information provided by 2DUS is consistent, in most cases, with the diagnostic results from 3DUS.
The diagnostic benefit of volume sonography critically depends upon expectations of the examiner and the precise reason why the scan itself is being performed. Although most patients relate to this technology from its ability to display a fetal face for bonding purposes, this is not a recognized medical indication in low-risk pregnancies. In this context, one must recognize that 3DUS has the potential to reveal much more than a fetal face. The fundamental technologies, as described in the Chapter 47, actually represents several different image visualization tools that may or may not apply to the question being asked. They include multiplanar imaging, surface rendering, volume rendering, thick-slice scanning, tomographic slices, inversion mode, and 3D Doppler ultrasonography (Figures 46-1, 46-2, 46-3, 46-4, 46-5, 46-6, 46-7). As one example, the maximum intensity projection algorithm might be the most appropriate to analyze a possible hemivertebra that is suspected on the 2D scan. Complementary display modes, such as multiplanar imaging or the use of parallel tomographic slices, might also offer benefit. By comparison, a surface-rendering algorithm would not be expected to provide useful information for bony structures such as cranial sutures or spinal abnormalities. This modality would be better suited for delineation of soft tissue problems such as cleft lip. Some volume analysis software packages allow the examination of volume reconstructions using a combination of different rendering algorithms (Figure 46-8). Others may use 4DUS for evaluating the status of joint movement of the wrist in a fetus suspected of having arthrogryposis. Hence, the examiner must remember to formulate one or more specific questions that are based on the initial 2D scan in order to choose the most appropriate type of image analysis.
Figure 46-2.
Volume sonography. Composite images demonstrate the versatility of 3DUS for surface and volume rendering examples (top left to right panels) of a normal 14-week fetus, normal fetal circulation, and bilateral cleft lip. Bottom images (left to right) represent normal cardiac ventricles and their anatomic relationships on the basis of 3D power Doppler ultrasonography, a dilated urinary collecting system using 3D inversion mode, and acardiac twin.
Figure 46-4.
Volume contrast imaging fundamentals. A coronal view of the fetal mouth and nostrils can be better visualized from using a thick scanning plane that includes thicker voxels. The surrounding facial tissue is collectively displayed with a wider depth of field and varying degrees of transparency assigned to each voxel.
Figure 46-6.
Parallel image slices. Serial and parallel image slices through a volume data set are used to display left and right club foot abnormalities in the top and middle frames of the first two rows. This output display modality is variably known as Tomographic Ultrasound Imaging (GE Healthcare), iSlice (Philips Medical Systems), Multi-Slice View (Samsung), and Multi-Slice (Siemens Medical Solutions).
Figure 46-7.
Three-dimensional power Doppler ultrasonography. Fetal circulatory structures include the umbilical vein, ductus venosus, hepatic veins, inferior vena cava, heart, aortic arch, and neck vessels in relation to surrounding anatomic structures such as the fetal spine and umbilical cord (A). A variation of this power Doppler technique (HD-Flow, GE Healthcare) can also be used to provide additional information about blood flow direction and velocity in a case of marginal placental cord insertion (B). (Adapted with permission from Lee W, Kalache KD, Chairworaponga T, et al. Three-dimensional power Doppler ultrasonography during pregnancy. J Ultrasound Med. 2003;Jan;22(1):91-7.)
Figure 46-8.
Customization of surface rendering algorithms. Advances in visualization software technology allows the examiner to apply surface-rendering algorithms to volume data sets in a manner that combines various rendering techniques, depending on the anatomic structures being emphasized. (Used with permission from Dr Luis Gonçalves.)
Although much emphasis has been placed on volume rendering, one must appreciate how useful it is for an examiner to analyze multiplanar image slices from standardized orthogonal views. In our practices, it is not uncommon that we might use this modality as the initial method of fetal organ evaluation. After standardized orthogonal planes are displayed, it is possible to systematically “march” through a volume of interest in order to better characterize the anatomy. One of the most common applications for this modality will be demonstrated for the fetal face evaluation. From these views, it will also be possible to make a wide variety of quantitative distance, angle, and area measurements as needed.
Good Two-Dimensional Imaging Is Likely to Translate to Satisfactory Three-Dimensional Volume Acquisitions
The most useful volume data sets will be acquired when optimal sonographic technique is used in pregnancies where technical factors do not degrade the image. Remember the basics by adjusting scanning parameters such as system gain and acoustic focus. A reasonable goal is to adjust the region of interest (ROI) in the rendering box so that it fills about two-thirds of the available display screen. Scan from different viewing perspectives for optimal images of the specific ROI. For example, the fetal spine and overlying skin line should be obtained from a prone fetus, not from the supine position.
We are often asked, “Is the sonographer’s job at risk if all one needs to do is to place a transducer on the maternal abdomen and push a start button?” The answer is emphatically, “NO!” because the likelihood that volume sonography will provide an adequate means for diagnostic interpretation is really dependent on the original quality of the images. The examiner should be able to optimize the image by utilizing the proper probe position while making certain that excessive pressure is not placed on the maternal abdomen. There are several ways to analyze good-quality volume data sets if the original acquisition is obtained under optimal conditions. Careful attention should be paid to adjusting image depth, acoustic focus, and signal gain at a time when fetal movement is minimal for acquisition of this image data. Both 2DUS and 3DUS techniques, however, are sensitive to the potentially detrimental effects of maternal obesity, fetal movement, early fetal age, presence of maternal abdominal scars, and oligohydramnios.
With these caveats in mind, some of the more common diagnostic applications will now be reviewed to further demonstrate basic approaches for using volume sonography during pregnancy.
The first trimester 2D scan is mainly performed for dating early pregnancies, confirming cardiac activity, and to measure NT as part of risk assessment for aneuploidy. Relatively few investigators have used conventional 2D imaging techniques to evaluate anatomic structures of the developing embryo. An important advantage of accurate early diagnosis would include parental reassurance that a major abnormality was not present. Earlier anomaly detection would provide more time for defining pregnancy options, prenatal care, delivery plans, and prognosis. As the field of fetal therapy develops, the earlier diagnosis of certain types of anomalies may even allow treatment at a time when chances for salvaging the fetus may be higher at an earlier stage of disease progression.
Several investigators have used 2D endovaginal scans to visualize fetal anatomy before 14 weeks’ menstrual age.3-5 First trimester pregnancies can also be evaluated using 3DUS, although recent improvements in high-frequency probe technology have made it increasingly feasible to visualize cross-sectional and surface anatomy of the embryo (Figure 46-9). Blaas et al6 were among the first groups to use 3DUS for volume reconstruction of embryos between 7 and 10 weeks’ menstrual age. They used a customized 7.5 MHz annular array vaginal probe and a VingMed system to trace contours of embryonic brain structures that permitted volume calculations as well.
Normal embryonic anatomy has also been studied using 3DUS.7 One investigator threaded a catheter-based 20-MHz ultrasound transducer through the maternal cervix and endometrial cavity to demonstrate the embryonic face, limbs, and brain.8 Benoit et al9 introduced the term, “sonoembryology” for describing the specific use of volume sonography of the developing fetus. He later demonstrated the evolving changes in embryonic brain development and reported that the optimal time to use 3DUS was between 7 and 12 weeks.10 Twelve representative images of the rendered volume provided an informative timeline of embryonic brain development (Figure 46-10). There have also been several related reports of conjoined twins,11-13 spina bifida,14 holoprosencephaly,10,15-18 sirenomelia,19 and sacrococcygeal teratoma.20
Figure 46-10.
Twelve representative volumes arranged by gestational age. The first and fourth columns are strict sagittal sections obtained with volume contrast imaging, with sections 1- to 2-mm thick. The second and fifth columns are strict right lateral views of the dissected ventricular system, and the third and sixth columns are anteroinferior views (≈45 degrees from the longitudinal axis of the metencephalon). The white bars used for length reference on the left edges of the images in the first and fourth columns are 10-mm long. The reference dots on the left of each 3D rendering are 5-mm apart. The ages of the embryos are 7 weeks 4 days (crown–rump length [CRL], 13.6 mm) and 7 weeks 6 days (CRL, 14.6 mm) in the first row; 8 weeks 1 day (CRL, 16.5 mm) and 8 weeks 3 days (CRL, 19.1 mm) in the second row; 8 weeks 6 days (CRL, 22.5 mm) and 9 weeks 2 days (CRL, 25.3 mm) in the third row; 9 weeks 4 days (CRL, 28.1 mm) and 9 weeks 6 days (CRL, 30 mm) in the fourth row; 10 weeks 6 days (CRL, 39.1 mm) and 11 weeks 1 day (CRL, 42.2 mm) in the fifth row; and 11 weeks 5 days (CRL, 49.2 mm) and 12 weeks (CRL, 53.3 mm) in the sixth row. (Reproduced with permission from Kim MS, Jeanty P, Turner C, et al. Three-dimensional sonographic evaluations of embryonic brain development. J Ultrasound Med. 2008;Jan;27(1):119-24.)
Although the sensitivity of 2DUS for the detection of major fetal anomalies between 11 and 14 weeks has been reported to be approximately 50%,21 there are many factors that can affect diagnostic results. They include the population being studied, type of equipment used, examiner experience, exam duration, and the gestational age at which the scan is performed. Unfortunately, no large-scale comparative studies have been performed that can clearly define the role of 3DUS for the systematic detection of fetal anomalies during early pregnancy as compared to 2DUS. Technical improvements, such as the development of more sophisticated image analysis tools or the commercial availability of higher-frequency transducers, are likely to result in more accurate and earlier diagnoses over time. The best diagnostic technology in the world, however, will not be translated into improved outcomes unless clinical management protocols are also capable of taking advantage of this information.
How much additional benefit is actually provided by 3DUS over conventional 2DUS during early pregnancy? Michailidis et al22 compared real-time 2D scans (5-MHz transabdominal and 7-MHz transvaginal probes) to 3DUS (7-MHz transvaginal probe) for early fetal anatomic assessment. The anatomic survey included the head, face, stomach, abdominal wall, kidneys, bladder, spine, and extremities in 159 consecutive women at 12.0 to 13.9 weeks’ gestation. Two 3D volumes were obtained at the end of the procedure, and they were subsequently analyzed for the same anatomic features that were examined using 2DUS. A “complete” anatomic survey was possible in 93.7% of the 2D scans, which was a higher visualization rate than 80.5% of fetuses that were satisfactorily examined using 3DUS (P <.001). The mean time to perform a 2D scan was 12.2 ± 3.4 minutes (SD) as compared to the greater time it took to acquire and analyze 3D volume data sets for the same information (8.4 ± 1.5 minutes) (P <.001). They concluded that real-time 2DUS was the best way to examine first trimester embryonic anatomy. Volume sonography provided occasional views that were not possible using 2DUS, was associated with less scanning time, and provided a mechanism where scanned data could be stored for subsequent review.
Fauchon et al23 performed a prospective study where an examiner acquired transabdominal 3DUS of the entire fetus from 273 singleton pregnancies between 11.0 and 13.9 weeks’ menstrual age. Each data set was manipulated and analyzed by two independent examiners who were blinded to each other’s results. The requirements for sonographic visualization of 12 anatomic structures were strictly defined. Crown–rump length and NT were measured with a high degree of agreement between both investigators in 100% and 84.6% of cases, respectively. Negligible clinical differences in either measurement resulted among all three examiners. In this study, a single abdominal 3DUS acquisition of a fetus between 11 and 13 weeks’ gestation usually provided satisfactory views for both the anatomic survey and NT measurement of the embryo. Increasing maternal weight was an important factor that prevented adequate visualization of embryonic anatomy, whereas longer crown–rump length increased the odds of the examiners being able to identify half of these anatomic characteristics.
The aforementioned studies indicate that the entire fetus can usually be satisfactorily screened for an anatomic survey during early pregnancy. Factors such as embryonic position, bladder filling, examiner experience, type of equipment used, menstrual age, limited range of probe movement, transducer frequency, and even maternal obesity can greatly influence the examiner’s ability to complete this transvaginal study. The advantages for using a high-frequency transvaginal probe to improve image resolution is offset by relatively limited tissue penetration. It also becomes increasingly difficult to capture the entire fetus after approximately 14 weeks’ menstrual age. After this time, it may be necessary to acquire more than one volume data set due to the technical specifications of most mechanical volume probes. Accordingly, one could subsequently attempt volume acquisitions with a lower frequency abdominal probe. More studies are required to characterize the normal appearance and evolution of embryonic structures on the basis of 3DUS. For example, the physiologic mid-gut herniation and its relationship to development of ventral wall defects is well known. This normal finding is typically very prominent in a 10-week fetus (see Figure 46-9).
Several sonographic markers of genetic risk have included an evaluation of NT, nasal bone, frontomaxillary facial angle, fetal pelvic measurements, and embryonic volume. Key questions must be considered before these new techniques are introduced into clinical practice. First, the technique must be relatively simple to perform, affordable, and reproducible among different examiners. Second, the relationship of these measurements to menstrual age must be established. Third, the new marker should be able to distinguish between normal and pathologic pregnancies with good sensitivity and a relatively low false-positive rate. Fourth, any potential advantages over the use of conventional 2DUS and any technical limitations of the new technique should be described.
At least six reports have examined how 3DUS can be used to evaluate nuchal translucency.24-29 Paul et al27 studied 40 consecutive uncomplicated pregnancies that underwent first-trimester screening for Down syndrome at 11 to 14 weeks. NT was measured using both transabdominal 2DUS and 3DUS. Two volume data sets were acquired—one that included a midsagittal plane and a second one that was obtained from a random initial plane. This detail is important because images that are analyzed from the original plane of acquisition are usually the clearest because they do not require reconstruction. Small but significant errors can occur if the NT thickness is in the range of the ultrasound beam’s lateral resolution of 1 to 2 mm. They found that NT thickness could be repeated in 38 of 40 (95%) of the volumes that were acquired from a sagittal view of the fetus. By contrast, the random volumes yielded only 24 of 40 embryos with satisfactory NT measurements. The mean difference between results from 2DUS and those obtained from reslicing “sagittal” volume data sets was –0.097 mm (95% limits of agreement from –0.481 to 0.675) and 0.225 mm (95% limits of agreement from –0.369 to 0.819) when random volumes were analyzed. Their results underscored the fact that the analysis of 3D volume data sets can be reliably used to replicate NT measurements only when the nuchal skin line is also seen on the 2D scan. If visualization of the posterior neck is obscured by acoustic shadowing, one would not expect a well-defined NT on the multiplanar reconstruction.
Clementschitsch et al28 also prospectively examined 229 unselected pregnancies to compare the use of 2DUS and 3DUS for NT measurements. Satisfactory NT measurements were obtained using 2DUS in 96.8% of cases as compared to 3DUS (98.6% transabdominal). Suboptimal fetal position was the main reason why 2DUS failed to provide satisfactory measurements. In some cases, it was difficult to precisely distinguish between fetal skin and amnion or uterine wall (6.3% for 2DUS, 3.3% for 3DUS). Fetal movement was the main reason for measurement failure using 3DUS. The mean time for either method was similar (9 minutes for 2DUS vs 10 minutes for 3DUS). Finally, the correlation between these measurements was very high (r = 0.97).
Both studies suggest that reliable NT measurements are feasible with transabdominal 3DUS in the 11- to 14-week embryo, especially if the original plane of volume acquisition contains a midsagittal view of the embryonic neck. Of course, it would be prudent to follow technical guidelines for 2DUS that are recommended by the Foundation for Fetal Medicine (http://www.fetalmedicine.com/ultrasound-scans/nuchal-scan) or the Nuchal Translucency Quality Review (NTQR; http://www.ntqr.org) programs to ensure adequate quality control of these precise measurements. Presently, only the latter program addresses the use of 3DUS for NT measurement. The NTQR guidelines suggest that volume data acquisitions for this purpose are most reliable from a sagittal sweep of the embryonic face. Examiners are also cautioned about the potential limitations of lateral resolution for their ultrasound system.
Can reliable NT measurements be obtained from volume data that are not originally acquired from a sagittal plane? Shipp et al30 addressed this question by analyzing NT measurements of 29 consecutive fetuses between 11.4 and 13.9 weeks’ menstrual age. The 2DUS results were compared to 3D-based measurements from a median sagittal plane of the embryonic neck. A sagittal plane was obtained by navigating through 3D multiplanar views using volume data sets that had been initially acquired from a coronal sweep of the embryo. The mean measurement (SD) using 2DUS (1.7 ± 1.4 mm) was not statistically different from use of a reconstructed sagittal plane (1.8 ± 1.6 mm) (P = .4), and these results were highly correlated (r = 0.98, P <.001). Their findings suggest that NT measurements are feasible from 3D data, despite that the original volume was initially acquired from a coronal plane. They also concurred with an earlier report that emphasized the importance of satisfactorily visualizing the neck region using 2DUS before initiating the volume sweep procedure.27 The interpretation and practical implementation of their findings warrant further investigation in a larger group of patients. Furthermore, the study did not consider the skill of the examiner for satisfactory manipulation of these volume data sets in a reproducible manner.
The fetal nasal bone also has been found to be a sonographic marker of genetic risk. Cicero et al31 used conventional 2DUS to identify the absence or presence of nasal bone in fetuses with trisomy 21 at 11 to 13+6 weeks’ gestation. The nasal bone was absent in 113 (0.6%) of the 20,165 chromosomally or phenotypically normal fetuses and in 87 (62.1%) of the 140 fetuses with Down syndrome. The inclusion of the nasal bone in first trimester combined screening for trisomy 21 achieved a detection rate of 90% for a false-positive rate of 2.5%. Another 2DUS study32 observed a much lower rate of absent nasal bone in an unselected (16.7%) and selected (46.7%) population of fetuses between 11 and 13.9 weeks’ menstrual age. Because this study did not utilize any formal training or quality assurance program for the detection of nasal bone, Sonek et al33 recommended that an ultrasound marker, such as the nasal bone, should not be used in a screening program unless the examiners are adequately trained. In an earlier study, Cicero et al34 analyzed the ability of 15 sonographers for obtaining satisfactory views of the nasal bone. They found that approximately 80 2D examinations were required to achieve competency for nasal bone assessment during the routine 11- to 14-week scan. In this context, Malone et al35 performed nasal bone imaging as a screening tool for aneuploidy in 6324 of 38,189 patients who were scanned at 10.4 to 13.9 weeks’ menstrual age. An acceptable nasal bone image was reported in 76% of cases. Nasal bones were present in 4779 (99.5%) of this subgroup and absent in 22 fetuses (0.5%). Absence of nasal bones had sensitivity for aneuploidy of only 7.7% with a false-positive rate of 0.3% and positive predictive value of 4.5%. They concluded that nasal bone evaluation was not useful for population screening for trisomy 21, possibly because of the difficulty in performing this assessment consistently in a general US population setting. However, one-quarter of these sonographers reported unsatisfactory visualization of the nasal bone despite specific training in first trimester sonography. These results seemed contrary to their specific implementation of a quality control program to monitor ongoing performance of nasal bone sonography. Nonetheless, it is presently unclear as to why the FASTER trial results in the United States did not confirm the utility of nasal bone screening in the United Kingdom.
Does 3DUS provide additional diagnostic benefit for nasal bone evaluation during early to mid-pregnancy? Rembouskos et al36 found that a midsagittal view was the best original plane of 3D volume acquisition, and their results suggested that satisfactory visualization of the nasal bone was optimal when the fetal profile was insonated at about 45 degrees. The likelihood of an adequately visualized nasal bone from a 3D volume data set was strongly related to the quality of the initial 2D image. Other investigators37,38 have used 3DUS to document the presence of a gap between the nasal bones during early pregnancy. Peralta et al38 used 2DUS and 3DUS to scan 450 fetuses between 11.0 and 13.9 weeks’ menstrual age. They found sonographic evidence of this gap in about 20% of fetuses. Furthermore, in about 40% of these cases, the nasal bone may erroneously be interpreted to be absent in an optimal median sagittal plane.
Gonçalves et al39 used 3DUS to evaluate nasal bones in 26 fetuses with Down syndrome during the second trimester of pregnancy (Figure 46-11). Rendered facial profile views demonstrated absent nasal bones in 18.9% of cases, of which 90% had Down syndrome for an overall sensitivity of 34.6% and false-positive rate of 3.7%. This appearance was associated with a 9.3-fold increased risk for Down syndrome when compared to the normal control group. By comparison, 3 ossification patterns were demonstrated from coronal views of the rendered face: (1) normally developed, (2) delayed ossification, and (3) absent nasal bones. Sensitivity, false-positive rate, and likelihood ratio of absent nasal bones for detecting Down syndrome were 34.6%, 3.7%, and 9.0% (95% CI = 1.3–68.7), respectively. These investigators identified nasal bones with delayed ossification by using this maximum-intensity projection algorithm. Similar to findings from 2DUS, the absence of nasal bones was associated with the highest risk of Down syndrome. Delayed nasal bone ossification patterns were associated with a somewhat lower risk for these abnormal fetuses. The sensitivity, false-positive rate, and likelihood ratio of delayed ossification for detecting Down syndrome were 42.3%, 22%, and 1.83% (95% CI = 0.8–4.4), respectively. This “hypoplasic” pattern probably reflects shortened nasal bones that have been described using 2DUS.40 Benoit and Chaoui41 subsequently used the 3D maximum intensity projection algorithm to demonstrate unilateral absence or hypoplasia of nasal bones during the second trimester of pregnancy. An analysis of these nasal bone patterns may improve our ability to identify fetuses at risk for Down syndrome. However, more experience with these methods is required in an unselected patient population before the diagnostic significance of 3DUS can be established for this purpose.
Figure 46-11.
Nasal bone patterns using maximum intensity projection. Summary of nasal bone ossification patterns observed on three-dimensional reconstruction of the fetal skull using the maximum-intensity projection mode. A: Normal. B: Delayed ossification or hypoplastic. C: Absent nasal bones. (Reproduced with permission from Gonçalves LF, Espinoza J, Lee W, et al. Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with Down syndrome—description by 3-dimensional ultrasonography and clinical significance. J Ultrasound Med. 2004;Dec;23(12):1619-1627.)
Frontomaxillary facial angle (FMF) is another sonographic marker of fetal aneuploidy that has been studied in both the first and second trimesters of pregnancy. This measurement is defined as the angle between the upper surface of the upper palate and the frontal bone from a median sagittal view of the fetal face (Figures 46-12 and 46-13). Sonek et al42 used 3DUS to standardize this measurement, based on the hypothesis that the maxilla is dorsally displaced in relation to the forehead in fetuses with trisomy 21 between 11.0 and 13.9 weeks’ menstrual age. The FMF angle was significantly larger in the abnormal group of 100 fetuses with Down syndrome (mean 88.7, range 75.4–104 degrees) as compared to 300 chromosomally normal controls (mean 78.1, range 66.6-89.5 degrees). This angle was also not significantly associated with NT. Subsequent work by the same group43 underscored the importance of standardizing the FMF measurement using 3D multiplanar views of the facial profile that includes the tip of the nose and the rectangular shape of the maxillary bone. This approach was used to demonstrate very reproducible results, and they were able to prospectively demonstrate that experienced examiners can alternatively measure the FMF angle using 2DUS as well.44 Furthermore, an increased FMF angle in fetuses at 11.0 to 13.9 weeks’ menstrual age is increased in cases of trisomy 13, but only when associated holoprosencephaly is present.45 A prospective study of 782 euploid fetuses and 108 fetuses with Down syndrome combined the FMF with biochemical screening tests.46 The inclusion of FMF angle to first trimester combined screening increased the estimated detection rate from 90% to 94% for a false-positive rate of 5%.
Figure 46-12.
Fetal profiles and facial angles (euploid and trisomy 21 fetuses). Ultrasound images of facial angle in (A), a euploid fetus, and (B), a fetus with trisomy 21. (Reproduced with permission from Sonek J, Borenstein M, Dagklis T, et al. Frontomaxillary facial angle in fetuses with trisomy 21 at 11-13+6 weeks. Am J Obstet Gynecol. 2007;Mar;196(3);271.e1-4.)
Figure 46-13.
Graphs of facial angle measurements (euploid and trisomy 21 fetuses). Graphs of facial angle measurements in (A), euploid fetuses, and (B), trisomy 21 fetuses, with their corresponding crown–rump lengths, are plotted on the reference range (mean and 95th and 5th percentiles). Normal ranges (mean and 5th and 95th percentiles) are shown. (Reproduced with permission from Sonek J, Borenstein M, Dagklis T, et al. Frontomaxillary facial angle in fetuses with trisomy 21 at 11-13+6 weeks. Am J Obstet Gynecol. 2007;Mar;196(3);271.e1-4.)
Molina et al47 also applied the FMF angle to 150 normal fetuses and 23 fetuses with Down syndrome between 16 and 24 weeks’ menstrual age. In the normal group, the FMF angle did not change with menstrual age, and the 95th centile was 88.5. By comparison, the FMF angle was greater than 88.5 degrees in 65.2% of abnormal fetuses, and interobserver analysis indicated that in 95% of cases, the difference in measurements between examiners was less than 5 degrees. Technically, one must differentiate between the bony palate and vomer from a median sagittal view of the facial profile for optimal FMF measurements (Figures 46-14 and 46-15).
Figure 46-14.
Sonographic anatomy of the fetal profile, hard palate, and vomer. Ultrasound images of a normal fetal profile at 12 weeks (A), 16 weeks (B), and 20 weeks (C) of gestation. At 12 weeks, the palate (P) and vomer (V) appear as a single hyperechogenic rectangular structure, but in the second trimester there are two echogenic structures. The inferior one, which is directed toward the basilar portion of the occipital bone posteriorly, represents the palate. The vomer is the superior one, with an irregular convex shape on the top, and is directed toward the sphenoid bone posteriorly. (Reproduced with permission from Molina F, Persico N, Borenstein M, Sonek J, Nicolaides KH. Frontomaxillary facial angle in trisomy 21 fetuses at 16-24 weeks of gestation. Ultrasound Obstet Gynecol. 2008;Apr;31(4):384-387.)
Figure 46-15.
Ultrasound image of a normal fetal profile at 20 weeks demonstrating the measurement of the frontomaxillary facial angle. (Reproduced with permission from Molina F, Persico N, Borenstein M, Sonek J, Nicolaides KH. Frontomaxillary facial angle in trisomy 21 fetuses at 16-24 weeks of gestation. Ultrasound Obstet Gynecol. 2008;Apr;31(4):384-387.)
Since the late 1990s, several studies have correlated iliac angles—from a 2D axial view of the fetal pelvis—with the risk of Down syndrome.48-50 Bork et al50 showed how from a cohort of 377 singleton fetuses, the mean iliac angle for normal fetuses (68.2 ± 15.4 degrees) was significantly lower than observed in abnormal fetuses (98.5 ± 11.3 degrees). A receiver–operator curve for their high-risk population identified an optimal cutoff of 90 degrees for a detection rate of 90.9% (5.5% false-positive rate). These findings were supported by Shipp et al,51 as in their prospective cohort of 19 fetuses diagnosed with Down syndrome, the mean iliac angle was 80.1 ± 19.7 compared to 63.1 ± 20.3 degrees for the 1167 normal controls. Despite their results, it was concluded that the iliac angle alone was not useful in a high-risk population because of a high false-positive rate of 12.9%. French investigators also found a similar high false-positive rate of 20% for use of the iliac angle as a single marker for trisomy 21.52 Massez et al53 examined the effect of fetal position on the iliac angle measurement using 2DUS in 695 fetuses during the mid-trimester. In euploid fetuses, the mean iliac wing angle was 83.7 degrees in decubitus and 68.7 degrees in the lateral position. In fetuses with trisomy 21, the mean angles were 104.9 and 102.5 degrees, respectively.
A relatively high false-positive rate of prior studies that utilized 2DUS may have been largely attributed to the complex structure of the fetal pelvis. To address this possibility, Lee et al54 used 3DUS to standardize iliac angle measurements from multiplanar views of the fetal pelvis. Thirty-five normal fetuses and 16 fetuses with trisomy 21 were scanned during second trimester amniocentesis. The mean iliac angle for normal fetuses was 79 ± 5.5 degrees, which was significantly less than the abnormal fetuses (87.7 ± 4.9 degrees) (P <.001). Intraclass correlation analysis suggested that this technique was reproducible between examiners. For a false-positive rate of 5%, an axial iliac angle threshold of 87 degrees alone correctly classified 56% of fetuses with trisomy 21 in this high-risk group. A subsequent study described how skeletal rendering of the fetal pelvis can be used to reproducibly measure both axial and coronal iliac angles for predicting risk of Down syndrome. The multiple regression model had a sensitivity of 94.4% for a false-positive rate of 5% in the detection of fetuses with trisomy 21 from a selected high-risk population.55 Further studies will be required to improve our understanding of the potential utility for iliac angle measurements for an unselected low-risk population during the second trimester of pregnancy.
Falcon et al56 used 2DUS and 3DUS to measure fetal trunk and head volume in 140 chromosomally abnormal fetuses at 11.0 to 13.9 weeks’ menstrual age and compared them to 500 normal controls. In 72 fetuses with trisomy 21 and 14 fetuses with Turner syndrome, the crown–rump length (CRL) for gestation was similar, but the fetal trunk and head volume was about 10% to 15% lower. In fetuses with trisomy 18 (n = 29), trisomy13 (n = 14), and triploidy (n = 11), the deficit in volume was about 45%, as compared to CRL, which was lower by less than 15%. These results raised the possibility that fetal trunk and head volume measurements may have advantages over 2DUS for the identification of early fetal growth abnormalities. The same research group used similar techniques to show that early asymmetric growth restriction between the trunk and head was characteristic of triploidy, trisomy 13, and trisomy 18.57 By comparison, the growth abnormalities equally affected the head and abdominal volumes in fetuses with trisomy 21 and Turner syndrome.
Several 3D volume analysis tools can be applied to the fetus. Although we are trained to mentally translate 2D images into 3D representations, this traditional approach is limited by the examiner’s prior experience and ability to interpret this information. Furthermore, there are new volume analysis tools that permit us to visualize images in ways that are not possible using conventional methods. Despite these possible advantages, many diagnostic imaging cases can be simply evaluated from using only 2DUS. In some instances, 3DUS offers a complementary approach that may improve diagnostic confidence for the diagnostic impression that is initially based on conventional sonography.
We currently use 2DUS for the prenatal detection of most congenital anomalies, with a targeted application of 3DUS to answer specific questions that are raised from the initial diagnostic impression. As more applications for 3DUS are described against an emerging backdrop of technological improvements, the paradigm for how volume sonography is applied to obstetrical practice may also evolve.58 For example, Benacerraf et al59 have described how 3DUS improved the workflow of clinical practices by the efficient acquisition and review of volume data sets. Although this is not a focus of this chapter, several investigations have also proposed automating the analysis for data sets for the fetal heart.60-63 Others have reported remote sonographic diagnosis for telemedicine applications, using 3DUS in areas that are remote from the expert consultant.64-67 Volume sonography has also been used to assess fetal urine production in both normal fetuses68,69 and after laser surgery for a case of twin-to-twin transfusion.70
Many scientific articles have been published over the past decade as a result of the ultrasound manufacturing industry’s successful efforts to commercialize 3DUS technology into clinical practice. This process has not only included improved image quality, smaller transducers, and faster computers but the development of volume data analysis tools as well. Potential advantages and technical limitations of 3DUS will now be reviewed for selected obstetrical problems.
The fetal face is important because it can provide diagnostic clues for the presence of isolated abnormalities and genetic syndromes. Although many patients immediately recognize facial features from the surface-rendered display, we believe that 3D multiplanar images are often the most helpful for medical diagnosis. However, the most appropriate selection of volume analysis tools critically depends on the question being asked. For example, one would use the maximum-intensity projection algorithm to visualize problems with bony structures such as the cranial sutures. Soft tissue clefts might be well visualized with surface rendering. The lips and hard palate could be systematically evaluated by using multiplanar images as well. This modality allows the use of a reference dot to improve understanding of complex anatomic relationships that are being investigated. Others might want to confirm a specific finding by using a parallel-slice display (eg, tomographic ultrasound imaging, multislice, i-Slice), or even thick-slice scanning of the fetal lips (eg, volume contrast imaging). Therefore, one must choose the most appropriate set of volume analysis tools on the basis of the diagnostic questions that are clinically relevant.
Many early investigators pointed out the benefits of 3DUS in evaluating the fetal face.71-73 Pretorius et al74 described their preliminary experiences with visualizing the fetal face and lips using surface rendering and multiplanar views. In a subgroup of fetuses at less than 24 weeks’ gestation, 3DUS confirmed a normal lip in 93% (58 of 63 cases) as compared with 76% (48 of 63 cases) using 2DUS. At that time, they noted that the 3D images of cleft lip were easier to understand for both the family and clinical colleagues. Merz et al75 used multiplanar views of the face and found that the facial profile that was obtained by 2DUS represented the true midsagittal profile in only 69.6% of cases. In the remaining 30.4%, the profile view deviated from a true midsagittal section by up to 20 degrees in one or two planes. In this series, they found 20 of 25 facial anomalies that were demonstrated using both 2DUS and 3DUS. In the remaining five cases, 3DUS revealed additional anomalies that included two cases of narrow cleft lip as well as single examples of unilateral orbital hypoplasia, cranial ossification defect, and flat facial profile with decreased amniotic fluid volume. Such preliminary observations were quite extraordinary for the level of 3D technological development at that time. It was not until approximately 3 years later that the “electronic scalpel” image segmentation tool became commercially available on desktop computers.76 This tool permits the examiner to selectively remove surrounding voxels that prevent the precise display of volume-rendered structures.
One approach initially applies 4DUS to confirm recognizable features of the fetal face. The rendered algorithms provided by the equipment vendors are often excellent and provide a rapid acquisition of the face (Figure 46-16). Movement of the mouth is also easily demonstrated. Acquisition is optimal when the fetal face is acquired from the sagittal or profile view by placing the ROI box directly over the face, with the rendering line just anterior to the nose (Figure 46-17). The rendering line may be straight or curved to optimize the image. Occasionally it is necessary to increase the threshold knob to take away unwanted echoes, particularly in heavier patients. If the face cannot be positioned in a sagittal orientation, a frontal view (coronal) can be obtained, resulting in a rendered image that displays the profile of the fetus.
Static 3DUS acquisitions of the fetus generally provide better resolution than 4DUS acquisitions and are used for diagnostic evaluation. The face can be acquired from any orientation, but sagittal and slightly oblique off sagittal are optimal for seeing the rendered face en face. Optimal planes of acquisition for various facial structures are summarized in Table 46-1.
| Facial Structure | Optimal Plane of Volume Acquisition |
|---|---|
| Entire face | Sagittal or oblique off-sagittal |
| Primary and secondary palate | Axial |
| Lip | Coronal (frontal) |
| Profile | Sagittal |
| Orbits | Axial |
| Nasal bone | Sagittal |
| Ears | En face |
Manipulation of the 3DUS volume should begin with attempting to get the face into a standard, symmetrical orientation. The cursor dot should be placed on a midline structure, preferably the nose or the region in between the orbits. The volumes should be rotated in all three planes until the orbits are symmetrical. It can then be evaluated by moving up and down in parallel slices in each plane.
The face can also be displayed using a multislice technique that is similar to magnetic resonance imaging or computed tomography where parallel slices at discrete intervals are varied to demonstrate the anatomy. In a series of 142 patients, McGahan et al77 found that when starting at 3-mm intervals, there was minimal manipulation needed to show in the axial plane the orbits, maxilla (primary palate), and mandible on one screen. Finally, Rotten and Levaillant78 have nicely described how 2DUS and 3DUS can be systematically used to evaluate the fetal face.
Although there are no published series of cases of abnormal orbits, case reports and images in review articles have been published.79-81 The orbits can be measured from volumes acquired of the face to identify hypotelorism (Figure 46-18), hypertelorism, and micropthalmia. We have found 3DUS very helpful when the orbits are absent or very small (Figure 46-19).
Figure 46-18.
Hypotelorism in a 21-week fetus with holoprosencephaly. Multiplanar display of the head shows that the orbits are too close together in the upper left image, which is the axial plane. A normal face would have space the size of an orbit in between two normal orbits. Right-hand image is profiled against the uterus. Lower left image is the coronal plane.
Figure 46-19.
Micropthalmia in a fetus at 22 weeks’ menstrual age. Multislice display at 2-mm intervals showing the maxilla in the upper left image and the tiny, shallow orbits in the lower row, middle image. Multislice allowed the physician to be confident that the orbits were abnormal because she could examine the region of interest at varying slice intervals very carefully. This was confirmed after delivery and with magnetic resonance imaging.
Periorbital masses such as dacrocystocele,82 frontal encephalocele, glioma, hemangioma, and teratoma may be difficult to evaluate with 2DUS, and 3DUS can be helpful.83-85 Several authors have reported that 3DUS was useful in evaluating these entities and for showing parents the 3D images for counseling.83-85
Fetal ear abnormalities are often associated with aneuploidy (eg, trisomies 13, 18, and 21) as well as genetic syndromes such as Treacher Collins syndrome, Fraser syndrome, CHARGE association, and VACTERL association.86,87 The ears may be small, large, an abnormal shape, or in an abnormal position. Although 2DUS can be used to assess the fetal ears, 3DUS has been found to be extremely helpful (Figure 46-20). Shih et al86 evaluated 18 fetuses with abnormal ears, and using 3DUS and found the ear shape, ridge pattern, and helix development as well as cranial location, axis, and orientation of the ear was better recognized on 3DUS compared to 2DUS. Case reports of abnormal ears seen using 3DUS in fetuses with Treacher Collins syndrome have also been reported.88,89 Nomograms for ear length and width measurements obtained with 3DUS have been reported as a potential screening test for aneuploidy.87
The metopic suture lies in the midline of the face above the nasal bone and is the space where the frontal bones come together (Figure 46-21). Abnormal development of the metopic suture has been associated with facial dysmorphism, fetal brain malformations, chromosomal defects, and genetic syndromes.90
Figure 46-21.
Normal metopic suture at 25 weeks. Upper left image is a multiplanar sagittal view showing the facial profile. Upper right image is an axial view through the orbits. Lower left image is a multiplanar image in the coronal plane. Lower right image is a coronal skeletal-rendered image, showing a normal metopic suture, which separates the two frontal bones in the forehead.
The use of 3DUS to evaluate cranial sutures and fontanelles was first reported in 1994 by Pretorius and Nelson.91 Visualization of normal sutures has been reported in 120 cases by Dikkeboom et al92 and in 120 patients by Faro et al.93 In general, it is easier to visualize the sutures at earlier gestational ages. The metopic suture has also been evaluated in the first trimester.94,95 Holoprosencephaly is associated with an accelerated development of frontal bones and premature closure of the metopic sutures.94 Similar changes were not observed in fetuses with trisomy 21.95 Faro et al96 have also described the presence of a widened metopic suture in fetuses with Apert syndrome.
Chaoui et al90 later described four patterns of abnormal metopic suture development. The first pattern involved delayed development with a V- or Y-shaped open suture in normal fetuses at 12 to 16 weeks. A second pattern was a U-shaped open suture. The third pattern was premature closure of the suture in normal fetuses after 32 weeks. The fourth pattern resulted from additional bone between the frontal bones in fetuses with holoprosencephaly and agenesis of the corpus callosum. The other three patterns were observed in fetuses with facial defects involving the orbits, nasal bones, lip, palate, and mandible.
Despite some geographic differences, oral cleft defects are among the most common congenital abnormalities with a prevalence of approximately 2.0 per 1000 births during the mid-trimester of pregnancy.97 One large Norwegian study recently reported 101 fetuses or newborns with facial clefts in 49,314 deliveries. Twelve percent of the affected cases were associated with chromosomal abnormalities, and 18% were documented with syndromes.98 Cleft lip and palate were probably the main reasons that 3DUS was initially developed for the detection of fetal anomalies. Many papers have been written on the technique and benefits of 3DUS in evaluating the lip and palate. It assists in evaluating the presence, the extent, and the appearance for communication with the patient and her family. Subtle deformities can be precisely evaluated using a stationary volume, rather than a moving fetus. Chmait et al99 showed that even clefts, thought to be isolated on 2DUS and 3DUS, were found to be associated with abnormalities at birth in 22% (8 of 37) of fetuses.
Volumes are acquired from static 3DUS volumes to evaluate the lip and palate. Axial acquisitions angled slightly upward toward the top of the mouth are optimal for evaluation of the primary and secondary palate. Rendered images of the face are helpful to demonstrate the cleft lip to the family (Figures 46-22 and 46-23). Multiplanar imaging can be used to evaluate the primary palate and lip. Many of the early articles only used the multiplanar reconstruction to evaluate for cleft lip and palate.100,101 Johnson et al102 studied 28 fetuses with cleft lip with or without palate and found that 3DUS was able to identify the cleft palate more frequently (19 of 22) than 2DUS (9 of 22). They also found that management was changed using 3DUS in that some patients elected to terminate the pregnancy and others elected to carry the pregnancy when they had planned otherwise. In another study, Chmait et al103 evaluated 53 fetuses with cleft lip with or without cleft palate and found that the diagnostic accuracy was improved for cleft lip to 100% (53 of 53) using 3DUS versus 91% (48 of 53) using 2DUS, and for cleft palate it was 89% (47 of 53) for 3DUS versus 57% (30 of 53) for 2DUS. Wang et al104 also demonstrated how the use of a parallel-image-slice display format (“extended imaging”) can also be used to evaluate fetal cleft lip and palate.
Figure 46-23.
Cleft lip and midline cleft palate at 13 weeks’ menstrual age. Multiplanar view of bilateral cleft lip and midline cleft palate in fetus with holoprosencephaly and multiple anomalies associated with trisomy 13.
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