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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.
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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.60,61,62, and 63 Others have reported remote sonographic diagnosis for telemedicine applications, using 3DUS in areas that are remote from the expert consultant.64,65,66, and 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
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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.
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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, multi-slice, 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.
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Many early investigators pointed out the benefits of 3DUS in evaluating the fetal face.71,72, and 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 1 or 2 planes. In this series, they found 20 of 25 facial anomalies that were demonstrated using both 2DUS and 3DUS. In the remaining 5 cases, 3DUS revealed additional anomalies that included 2 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.
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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 44-16). 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 region of interest box (ROI) directly over the face, with the rendering line just anterior to the nose (Figure 44-17). 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.
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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 44-1.
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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 3 planes until the orbits are symmetrical. It can then be evaluated by moving up and down in parallel slices in each plane.
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The face can also be displayed using a multi-slice 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.
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Although there are no published series of cases of abnormal orbits, case reports and images in review articles have been published.79,80, and 81 The orbits can be measured from volumes acquired of the face to identify hypotelorism (Figure 44-18), hypertelorism, and micro-opthalmia. We have found 3DUS very helpful when the orbits are absent or very small (Figure 44-19).
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Periorbital masses such as dacrocystocele,82 frontal encephalocele, glioma, hemangioma, and teratoma may be difficult to evaluate with 2DUS, and 3DUS can be helpful.83,84, and 85 Several authors have reported that 3DUS was useful in evaluating these entities and for showing parents the 3D images for counseling.83,84, and 85
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Fetal ear abnormalities are often associated with aneuploidy (eg, trisomies 13, 18, 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 44-20). 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
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The metopic suture lies in the midline of the face above the nasal bone and is the space where the frontal bones comes together (Figure 44-21). Abnormal development of the metopic suture has been associated with facial dysmorphism, fetal brain malformations, chromosomal defects, and genetic syndromes.90
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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 have 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.
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Chaoui et al90 later described 4 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 3 patterns were observed in fetuses with facial defects involving the orbits, nasal bones, lip, palate, and mandible.
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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.
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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 (Figure 44-22). 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.
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The rendered display can also be used to evaluate the secondary (hard and soft) palate. Campbell et al105 first published the demonstration of the hard palate using a "reversed face" technique. He later wrote an informative editorial discussing issues related to evaluation of the hard palate with various rendering techniques.106 Platt et al107 described the "flipped face" technique to display the primary (alveolar ridge) and secondary (hard and soft) palate. This view emphasizes the palate with an upright face and viewing from an inferior direction, rather than superiorly (Figures 44-23 and 44-24). Faure et al108 described a similar technique to display the primary and secondary palate in 100 low-risk fetuses that showed how 3D reconstruction of the fetal palate can be correlated to anatomic specimens. Pilu and Segata109 studied 15 normal fetuses and 1 fetus with cleft lip and palate and showed that the secondary palate could be evaluated if the face was insonated at a 45-degree angle in the sagittal plane; in addition, they showed that the palate could be displayed on both axial and coronal planes (Figures 44-25 and 44-26). Faure et al110 also found that a 30-degree inclined axial plane appears to be useful for assessing the integrity of the fetal soft palate (Figure 44-27).
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These examples serve to demonstrate the versatility of high-quality voxel-based images for providing several options for the analysis of fetal anomalies. It is important to remember that scanning artifacts may lead to misinterpretation of these images. For example, Nelson et al111 have reported several artifacts related to both 2DUS artifacts being propagated through the volume and new artifacts related to 3D reconstruction, display, and scanning.
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An evaluation of the median facial profile can be performed using both multiplanar and rendered displays (Figure 44-28). The face should be rotated into a standard, anatomic orientation so that the face is symmetrical. Three-dimensional US has been shown to be useful in identifying abnormal profiles such as micrognathia (Figure 44-29), retrognathia, midface hypoplasia, and frontal bossing (Figure 44-30). Lee et al111 evaluated 9 cases of micrognathia and found that an oblique plane can lead to misinterpretation of a normal chin to be abnormal, and that prominent cheeks (eg, in diabetic mothers) and retrognathia can lead to an overcall of micrognathia.
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Evaluation of the fetal mandible can provide important diagnostic clues to the presence of genetic syndromes. By mid-2008, the Online Mendelian Inheritance in Man (OMIM) database cited 328 syndromes for micrognathia (small jaw) and 53 syndromes for retrognathia (posteriorly displaced jaw). From a clinical perspective, these jaw abnormalities can also be associated with obstructed airways and problems with feeding after birth. Toward this end, Rotten et al113 have described an objective approach for the assessment of abnormal jaw size and position using 3DUS.
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Micrognathia was defined on the basis of a ratio between the mandibular width (MD) to the maxillary width (MX). Both parameters can be measured on an axial plane, caudal to the cranial base, at the level of the maxillary or mandibular tooth buds. From an axial plane, a line was extended posteriorly, 1 cm from the anterior border of the tooth buds. The MD/MX ratio was obtained from these 2 measurements (Figure 44-31).
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Retrognathia was defined by an inferior facial angle (IFA) that resulted from the crossing of 2 lines (Figure 44-32):
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A "reference line," orthogonal to the vertical part of the forehead, drawn at the level of the synostosis of the nasal bones.
A "profile line," joining the tip of the mentum and the anterior border of the more protrusive lip.
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Their results demonstrated that micrognathia and retrognathia can be distinguished by the methods in this paper. The MD/MX ratio assesses mandible size, whereas the IFA evaluates mandible position. Although it is possible to obtain these measurements using 2DUS, the authors believed that 3DUS could be applied more easily for this analysis. Such improvements in our ability to more precisely diagnose congenital abnormalities may translate into improved therapeutic approaches and outcome.
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Three-dimensional ultrasound images of the embryonic brain6,9 have offered a fascinating insight into normal and abnormal development of the central nervous system. Similar to 2DUS, however, the fetal brain can be poorly visualized as a result of acoustic shadowing from the bony calvarium during the second and third trimester of pregnancy. A successful sonographic study of the brain often relies on the use of transvaginal sonography through a suitable acoustic window such as the anterior fontanelle.
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Some of the earliest reports on the use of 3DUS for the diagnosis of fetal brain abnormalities included unilateral megalencephaly, hydrocephalus, anencephaly, holoprosencephaly, Dandy-Walker cyst, enlarged cisterna magna, periventricular leukomalacia, agenesis of the corpus callosum, and cerebellar fusion.114,115, and 116 Subsequent investigators have described 3DUS with varying degrees of successful visualization for fetal brain evaluation. One important technique for fetal brain evaluation was originally introduced by Timor-Tritsch et al117 as the "three-horn view." This view can be used to demonstrate the anterior, posterior, and inferior horns by either 2DUS or 3DUS scans. This 3D technique requires acquisition of a volume data set, orthogonal multiplanar display of brain structures, and rotation or tilting of the midcoronal section to the left or right. The examiner is able to navigate through the volume data for an improved understanding of these anatomic relationships for telemedicine, consultative, and teaching purposes.118 Another approach, the transfrontal view, uses the frontal cranial suture as an acoustic window to examine midline cerebral structures with abdominal 3DUS.119 This view was easily obtained in 89% of 124 healthy fetuses between 19 and 24 weeks' menstrual age. Anatomic findings were similar to a median sagittal scan through the anterior fontanelle. The transfrontal approach can also be used to evaluate the fetal facial profile. Correa et al120 prospectively scanned 202 fetuses using abdominal 3DUS between 16 and 24 weeks' menstrual age. Acceptable cerebral multiplanar views were satisfactorily viewed by a sonologist who had expertise in neonatal cranial sonography in 92% of cases. The visualization rate for brain structures is summarized for the "3D multiplanar neuroscan" in Table 44-2. Pilu et al121 have also presented a very informative review that demonstrates how they use 3DUS to systematically evaluate the fetal brain.
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As the imaging resolution and visualization software improved, other investigators examined the fetal brain as well. Roelfsema et al122 applied the Virtual Organ Computer-Aided Analysis (VOCAL) technique to document median brain volume that increased from 34 mL at 18 weeks to 316 mL at 34 weeks' menstrual age. This represents a nearly 10-fold increase during the second half of pregnancy. Viñals et al123 later applied a thick-slice scanning technique (volume contrast imaging) to describe the normal appearance and dimensions of the fetal cerebellar vermis. Paladini and Volpe124 found that posterior fossa abnormalities can usually be characterized using 3DUS on the basis of key findings that include upward displacement of the tentorium, counterclockwise rotation, and vermian hypoplasia of the cerebellum. One group has even described how 3DUS findings over time (ie, four-dimensional ultrasonography or 4DUS) can be used to assess neurobehaviorial movements of the fetus.125 Roeflsema et al126 described the normal development of the fetal skull base and found that these measurements were reproducible between examiners. In another study, serial volume measurements of the fetal cerebellum were prospectively acquired in 52 normal pregnant women between 20 and 32 weeks' menstrual age.127 These volume measurements were taken every 2 weeks as a potential tool for fetal growth evaluation. All of these studies demonstrate the evolving applications of 3DUS for fetal brain assessment. In many cases, the diagnostic results from both 2DUS and 3DUS should be complementary to magnetic resonance studies of the fetal brain.128
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The prenatal diagnosis of spina bifida has steadily improved as a result of maternal serum α-fetoprotein screening and from the widespread use of ultrasonography. Corresponding advances in patient management have greatly reduced mortality, but have had minimal impact on long-term disability from neurological sequelae. This morbidity includes paraplegia, sensory deficits, spinal deformity, bowel dysfunction, and urinary incontinence.
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Accurate characterization of spina bifida relies on sonographic recognition of disrupted ossification centers and/or overlying skin from transverse and coronal views of the fetal spine. Sonography predicts the clinical severity of open spina bifida because neurological symptoms correlate with the anatomic level of the defect. Kollias et al129 reported that two-dimensional ultrasonography (2DUS) estimated the defect to within 1 vertebral segment in 79% of fetuses with spina bifida. However, 1 retrospective study of 171 consecutive cases of spina bifida found that only 29% of cases accurately identified the specific upper level of a spinal lesion using 2DUS.130 Other investigators have proposed that 3DUS may be used to further characterize spina bifida.131,132,133, and 134
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Optimal views can be generated by manipulation of a virtual cutting plane through a volume reconstruction of the fetal spine. Lee et al135 have proposed that 3DUS can be used as a semiquantitative technique for determining the anatomic level of this lesion. Multiplanar views are acquired using a volume probe from an axial sweep of the fetal spine (Figure 44-33). A coronal view of the lumbar and sacral spine is rendered with a maximum intensity projection (MIP) algorithm that primarily displays the bony spine. An electronic cutting plane is used to display orthogonal views of the volume-rendered spine, beginning at the spinal segment that is contiguous with the last fetal rib. As the examiner moves the cutting plane towards the sacral spine, simultaneous views of the axial spine and overlying skin line can be visualized. Other 3DUS techniques can be used to directly render the bony and soft tissue defects (Figures 44-34 and 44-35). Spinal defect levels obtained in this manner closely correlate with findings from both 2DUS and postnatal results. Although multiplanar views are generally more informative than rendered views for localizing these defects, their simultaneous use increases the likelihood that a spinal defect will be appropriately analyzed. This approach may improve the characterization of spina bifida by adding diagnostic information that is complementary to the initial assessment by 2DUS.
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Volume sonography offers an important method that allows the examiner to visualize fetal skeletal structures on the basis of a MIP technique. This software algorithm displays only the most echogenic structures and it is possible to mix varying degrees of volume-rendered soft tissue for the final output display. Pretorius and Nelson were among the first to use 3DUS to visualize cranial sutures and fontanelles136 as well as the thoracic skeleton.137 The same group later demonstrated the value of stereoscopic imaging for these 3D reconstructions in order to better visualize fetal bony structures.138
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One of the earliest applications of 3DUS for a fetal skeletal abnormality was described in a fetus with platylospondylic lethal chondrodysplasia.139 Yanagihara and Hata140 subsequently reported early experiences with a specially developed abdominal 3D transducer for visualizing skeletal structures in 42 normal fetuses and in 3 anencephalic fetuses. Garjian et al141 reported a small series of fetuses with skeletal dysplasia using this technology. The series included campomelic dysplasia, thanatophoric dysplasia, osteogenesis imperfecta, arthrogryposis, and short-limbed dysplasia. Surface rendering, volume rotation, and multiplanar displays were especially helpful in 3 of 7 cases, when compared to 2DUS. Multiplanar imaging was helpful for displaying a true median facial profile, and volume sonography provided a more global assessment of the skeletal anatomy. The MIP technique made it possible to identify scapular hypoplasia in a fetus with campomelic dysplasia. The added depth perception cues and ability to rotate volume data both facilitated increased appreciation of positional limb anomalies as well as improved visualization of the spine. Another series from Cedars-Sinai Hospital further described diagnostic advantages of 3DUS over 2DUS for additional skeletal dysplasias for evaluating fetuses with facial dysmorphism, relative proportion of appendicular skeletal elements, as well as the hands and feet.142 Benoit143 provided additional examples of the maximum-intensity mode for displaying normal skeletal structures, hemivertebrae, cranial sutures, spina bifida, hand digits, and cranial fontanelles (Figures 44-36,44-37,44-38, and 44-39).
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Ruano et al144 have reported the use of a novel technology, 3D helical computed tomography (CT), for the diagnosis of fetal skeletal anomalies between 27 and 36 weeks' menstrual age. There were 3 cases of achondroplasia, 2 cases of osteogenesis imperfecta type II, and 1 case of chondrodysplasia punctata. The correct diagnosis was made in 4 cases using 2DUS. Both 3DUS and 3D helical CT were used to make the correct diagnosis in all cases. However, 3D helical CT provided an advantage of imaging the entire fetus.