Applications of Advanced Ultrasound Technology in Obstetrics

Over the years, there have been several improvements in ultrasound technologies including high-resolution ultrasonography, linear transducer, radiant flow, three-/four-dimensional (3D/4D) ultrasound, speckle tracking of the fetal heart, and artificial intelligence. The aims of this review are to evaluate the use of these advanced technologies in obstetrics in the midst of new guidelines on and new techniques of obstetric ultrasonography. In particular, whether these technologies can improve the diagnostic capability, functional analysis, workflow, and ergonomics of obstetric ultrasound examinations will be discussed.


Introduction
Ultrasound is widely used in obstetric practice to detect fetal abnormalities with a view to provide prenatal opportunities for further investigations including genetic testing and discussion of management options. In 2010, International Societies of Ultrasound in Obstetrics and Gynecology (ISUOG) published the practice guidelines on the minimal and optional requirements for a routine mid-trimester ultrasound scan [1]. Recently, The American Institute of Ultrasound in Medicine (AIUM) suggests a detailed diagnostic second/third trimester scan for high-risk pregnancies [2], and fetal echocardiography for at-risk pregnancies [3]. ISUOG has published recent guidelines on indications and practice of targeted neurosonography [4,5]. Although the introduction of prenatal cell-free DNAbased screening for Down syndrome has changed the role of the first trimester scan, the latter should still be offered to women [6]. Around 50% of major structural abnormalities can be detected in the first trimester [7]. In addition, a recent study showed that a routine scan at around 36 weeks' gestation can detect around 0.5% of previously undetected fetal abnormalities, as well as fetal growth restriction (FGR) [8].
The detection rate of fetal abnormalities varies, depending on anatomy survey protocol, ultrasound equipment and setting, among other factors [9]. A high-resolution ultrasound can facilitate a detailed diagnostic scan and a first-trimester scan and allow the detection of a small or subtle abnormality [10][11][12]. Although a detailed diagnostic scan is not required for all pregnant women, the indications include family history of congenital malformation, maternal age 35 or above, gestational diabetes mellitus, artificial reproduction technology, body mass index >= 30, teratogen, fetal nuchal translucency >= 3mm, and many other conditions [2]. In the midst of such increasing standards of obstetric ultrasound examination, there is a demand on improving the diagnostic capability, functional analysis, workflow, and ergonomics. Over the years, there have been several improvements in ultrasound technologies including high-resolution ultrasonography, linear transducer, radiant flow, three/four-dimensional (3D/4D) ultrasound, speckle tracking of the fetal heart, and artificial intelligence. The aim of this review is to evaluate the use of these advanced technologies in obstetrics.

High-Resolution Ultrasonography
High-resolution ultrasonography includes the use of a high-frequency transducer, and the means of enhancing image and signal processing including harmonic imaging (HI), spatial compound imaging (SCI), and speckle reduction imaging (SRI). Compared to a transducer with the low-frequency range (2 to 5 MHz), a transducer with the highfrequency range (5 to 9 MHz) can allow for improved resolution though with limited tissue penetration. HI, utilizing the physics of non-linear propagation of ultrasound through the body tissues, can produce high-resolution images with few artifacts. SCI, combining multiple lines of sight to form a single composite image at real-time frame rates, can reduce angle-dependent artifacts. The use of SRI can reduce speckles or disturbances that result from the echo, which is projected from an ultrasound transducer.

Fetal Echocardiography and Targeted Neurosonography
ISUOG recommends the use of the highest possible transducer frequency to perform fetal echocardiography with a view to improve the likelihood of detecting subtle heart defects, albeit at the expense of reduced acoustic penetration [10] (Figure 1a-d and Video S1). The use of HI can improve the quality of ultrasound images, especially when the maternal abdominal wall is thick during the third trimester of pregnancy [11,13].

High-Resolution Ultrasonography
High-resolution ultrasonography includes the use of a high-frequency tra and the means of enhancing image and signal processing including harmonic (HI), spatial compound imaging (SCI), and speckle reduction imaging (SRI). Com a transducer with the low-frequency range (2 to 5 MHz), a transducer with the quency range (5 to 9 MHz) can allow for improved resolution though with limit penetration. HI, utilizing the physics of non-linear propagation of ultrasound thr body tissues, can produce high-resolution images with few artifacts. SCI, combin tiple lines of sight to form a single composite image at real-time frame rates, ca angle-dependent artifacts. The use of SRI can reduce speckles or disturbances th from the echo, which is projected from an ultrasound transducer.

Fetal Echocardiography and Targeted Neurosonography
ISUOG recommends the use of the highest possible transducer frequency to fetal echocardiography with a view to improve the likelihood of detecting sub defects, albeit at the expense of reduced acoustic penetration [10] (Figure 1a-d an S1). The use of HI can improve the quality of ultrasound images, especially when ternal abdominal wall is thick during the third trimester of pregnancy [11,13]. For a targeted neurosonographic examination, ISUOG recommends the use resolution transvaginal transducers whenever possible [5]. An alternative is to u  For a targeted neurosonographic examination, ISUOG recommends the use of highresolution transvaginal transducers whenever possible [5]. An alternative is to use highresolution transabdominal transducers with high frequency reaching 8-9 MHz [5]. The anatomy of the fetal brain is examined in details on a continuum of transverse, sagittal and coronal planes (Figure 2a- resolution transabdominal transducers with high frequency reaching 8-9 MHz [5]. The anatomy of the fetal brain is examined in details on a continuum of transverse, sagittal and coronal planes (Figure 2a-

Face and Neck
While the prenatal detection of cleft lip is high, the detection rate of subtle abnormalities of face such as low-set or posteriorly rotating ear, triangular face, down-slanting palpebral fissures, or a long and marked philtrum remains low [14,15]. These subtle abnormalities may be features of rare but severe genetic disorders such as 5p deletion syndrome or RASopathy, which require chromosome microarray analysis or targeted sequencing for RASopathy genes. As such, it is important to perform a detailed ultrasound scan to evaluate fetal face in fetuses especially if they have large NT, heart defects, or unusual findings [14,15]. High-resolution ultrasonography allows the clear visualization of facial profile, lens, nostrils, lips, maxilla, and ears (Figure 3a-d, Video S3a,b). Recently, a new sonographic sign, the 'superimposed line' sign, is suggested for evaluation of the secondary palate by assessment of the vomeromaxillary junction in the midsagittal view of the palate [16] (Figure 3a).

Face and Neck
While the prenatal detection of cleft lip is high, the detection rate of subtle abnormalities of face such as low-set or posteriorly rotating ear, triangular face, down-slanting palpebral fissures, or a long and marked philtrum remains low [14,15]. These subtle abnormalities may be features of rare but severe genetic disorders such as 5p deletion syndrome or RASopathy, which require chromosome microarray analysis or targeted sequencing for RASopathy genes. As such, it is important to perform a detailed ultrasound scan to evaluate fetal face in fetuses especially if they have large NT, heart defects, or unusual findings [14,15]. High-resolution ultrasonography allows the clear visualization of facial profile, lens, nostrils, lips, maxilla, and ears (Figure 3a-d, Video S3a,b). Recently, a new sonographic sign, the 'superimposed line' sign, is suggested for evaluation of the secondary palate by assessment of the vomeromaxillary junction in the midsagittal view of the palate [16] (Figure 3a).  Larynx and its movement can be assessed by prenatal ultrasound (Figure 4 and V S4). In at-risk fetuses such as those with laryngeal atresia [17] and congenital diaph matic hernia, prenatal ultrasound allows systematic examination of the larynx, inclu vocal cords to detect laryngeal anomalies [17,18].  Larynx and its movement can be assessed by prenatal ultrasound (Figure 4 and Video S4). In at-risk fetuses such as those with laryngeal atresia [17] and congenital diaphragmatic hernia, prenatal ultrasound allows systematic examination of the larynx, including vocal cords to detect laryngeal anomalies [17,18].  Larynx and its movement can be assessed by prenatal ultrasound (Figure 4 and Video S4). In at-risk fetuses such as those with laryngeal atresia [17] and congenital diaphragmatic hernia, prenatal ultrasound allows systematic examination of the larynx, including vocal cords to detect laryngeal anomalies [17,18].

Early Pregnancy Scan
Transvaginal ultrasonography is essential in the assessment of pregnancy of unknown location, which can be due to early pregnancy, miscarriage, or ectopic pregnancy. It is important to avoid making a false-positive diagnosis of miscarriage by using transvaginal sonography, careful measurement of mean sac diameter and crown rump length, and using safe cut-off values of these measurements in defining miscarriage [19]. A recent study showed that amniotic sac sign (the presence of amniotic sac without a live embryo) is a reliable marker of miscarriage [20]. While the presence of an extrauterine gestational sac with yolk sac and/or embryo with or without cardiac activity is indicative of ectopic pregnancy, the presence of an inhomogeneous adnexal mass ('blob' sign) or extrauterine sac-like structure ('bagel' sign) is very suggestive of a tubal ectopic pregnancy [21]. In women with prior Caesarean section, ultrasound features of Caesarean scar pregnancy including low implantation of the gestational sac within or in close proximity to a Caesarean scar as well as classical signs of placenta accreta spectrum disorders should be looked out for [22,23].

First Trimester Scan
ISUOG and recently, AIUM published the practice guidelines on first-trimester fetal ultrasound scan [24,25]. High-resolution ultrasonography allows the early assessment of fetal anatomy [11] (Figure 5a-d, Video S5a,b) and fetal malformations [12]. Fetal heart can be examined in the late first trimester [26], particularly with the use of color Doppler (Video S5c,d). ISUOG recommends using high-frequency (6-12 MHz) transvaginal ultrasound to examine fetal brain, especially if the focus is in the posterior fossa and the maternal abdominal wall is thick [5].

Early Pregnancy Scan
Transvaginal ultrasonography is essential in the assessment of pregnancy of un known location, which can be due to early pregnancy, miscarriage, or ectopic pregnancy It is important to avoid making a false-positive diagnosis of miscarriage by using trans vaginal sonography, careful measurement of mean sac diameter and crown rump length and using safe cut-off values of these measurements in defining miscarriage [19]. A recen study showed that amniotic sac sign (the presence of amniotic sac without a live embryo is a reliable marker of miscarriage [20]. While the presence of an extrauterine gestationa sac with yolk sac and/or embryo with or without cardiac activity is indicative of ectopi pregnancy, the presence of an inhomogeneous adnexal mass ('blob' sign) or extrauterin sac-like structure ('bagel' sign) is very suggestive of a tubal ectopic pregnancy [21]. I women with prior Caesarean section, ultrasound features of Caesarean scar pregnanc including low implantation of the gestational sac within or in close proximity to a Caesar ean scar as well as classical signs of placenta accreta spectrum disorders should be looke out for [22,23].

First Trimester Scan
ISUOG and recently, AIUM published the practice guidelines on first-trimester feta ultrasound scan [24,25]. High-resolution ultrasonography allows the early assessment o fetal anatomy [11] (Figure 5a-d, Video S5a,b) and fetal malformations [12]. Fetal heart ca be examined in the late first trimester [26], particularly with the use of color Dopple (Video S5c,d). ISUOG recommends using high-frequency (6-12 MHz) transvaginal ultra sound to examine fetal brain, especially if the focus is in the posterior fossa and the ma ternal abdominal wall is thick [5].

Doppler Ultrasound
Doppler ultrasound is widely used in obstetrics. ISUOG has made recommendations on how to perform Doppler ultrasonography of the fetoplacental circulation [27]. It is a challenge to detect late-onset feral growth restriction (FGR). Although third-trimestercerebroplacental ratio (CPR = middle cerebral artery pulsatile index/umbilical artery pulsatile index) is an independent predictor of stillbirth and perinatal mortality [28], CPR with or without adjustment for estimated fetal weight centile showed a low prediction rate for adverse perinatal outcome [29]. According to a meta-analysis, abnormal uterine artery (UtA) Doppler in the third trimester is useful in predicting perinatal death in suspected small-for-gestational age fetuses [30]. A recent prospective study suggested that cerebralplacental-uterine ratio (CPUR = CPR divided by mean UtA pulsatile index) detected FGR better than CPR or UtA Doppler alone [31].

Labour Ward Ultrasound
The use of intrapartum ultrasonography is increasing. It can be performed by using a portable machine equipped with a wide-sector and low-frequency (<4 MHz) transducer and batteries with a long life, and being quick to start up and recharge [32]. According to ISUOG practice guidelines [32], intrapartum ultrasound is indicated when there is slow progress or arrest of labor in the first or second stage. Recent studies showed that single ultrasound assessment of the fetal head station on admission in active phase or repeated measurements during active phase can predict the duration of labor and operative delivery in nulliparous women [33,34]. When the second stage of labor is prolonged, ultrasound can be used to assess fetal head position and station before considering or performing instrumental vaginal delivery [32]. Such assessment has a potential to predict mode of operative delivery and pregnancy outcomes [35]. Compared to clinical vaginal examinations, ultrasound assessment of the fetal head station and position is objective and reproducible [32][33][34], but assessment of cervical dilatation is limited when the dilatation is ≥ 4 cm and the membranes are ruptured [36].
Allowing detection of changes in tissue elasticity, elastography is a complementary technique to B-mode imaging, and it includes two methods, namely, shear-wave and strain elastography. A recent meta-analysis showed that the performance of cervical elastography was better than cervical length in the prediction of preterm delivery [37]. For the prediction of outcome of induction of labor, models based on inner cervical shear wave elastography and cervical length were more accurate than models based on the Bishop score [38].

Linear Transducer
With a high-frequency ultrasound, a linear transducer can produce high-resolution images of shallow structures and small parts. Unlike curved transducers, linear transducers produce a rectangular field of view with uniform beam density throughout all tissue levels and without divergence in deeper tissue. The use of a transabdominal linear transducer can enhance the examination of the spinal cord and conus medullaris in the midsagittal view of the spine [5]. Some abnormalities such as cataract [39] and laryngeal atresia [17] can be well demonstrated using a linear transducer.
A linear transducer can be used to examine fetal structures in the first trimester (Figure 6a-d). However, a linear transducer is not suitable for using if the structures of interest are deep or the maternal abdominal wall is thick. Although a linear transducer can allow the examination of the fetal cardiac anatomy at 11-13 weeks [40], it is the use of color flow mapping but not of a linear transducer that improves the examination [41]. Diagnostics 2021, 11, x FOR PEER REVIEW 7

Radiant Flow
Radiant flow shows the blood flow with a sense of depth by using a specific rithm to convert the index of erythrocyte density in a certain area into a height which is then superimposed on the initial coding of color, power Doppler, or high-d tion flow [42]. Other advantages include reducing blood overflow and indicating th sel with sharp edges. Special display produced by similar technologies include Micro Imaging (Philips), MV-Flow, and LumiFlow (Samsung).
Radiant flow is used to show fast blood flow in the fetal heart and brachycep arteries [42] (Videos S5d and S6a,b), as well as slow-blood flow in the neurovascula culation [43] (Video S7).
The fetal umbilical-portal venous system is complex. High-definition flow im (HDFI) has been used to assess the normal anatomy of this system or umbilical-p systemic venous shunts. Transverse and sagittal planes are used to examine the feta bilical-portal venous system (Video S8a,b). In a recent case report, the authors used and radiant flow imaging to clearly delineate the aberrant course of the ductus ve returning to the coronary sinus [44].

3D/4D Ultrasound
Over the years, new 2D modes (such as high-density power imaging), new 3D ume acquisition (such as Corpus callosum mode or matrix probe), and new analysis as semiautomated analysis) have been added in 3D/4D ultrasound examinations ( 1). The use of 3D multiplanar/multislice analysis facilitates the assessment of norma

Radiant Flow
Radiant flow shows the blood flow with a sense of depth by using a specific algorithm to convert the index of erythrocyte density in a certain area into a height index which is then superimposed on the initial coding of color, power Doppler, or high-definition flow [42]. Other advantages include reducing blood overflow and indicating the vessel with sharp edges. Special display produced by similar technologies include MicroFlow Imaging (Philips), MV-Flow, and LumiFlow (Samsung).
Radiant flow is used to show fast blood flow in the fetal heart and brachycephalic arteries [42] (Videos S5d and S6a,b), as well as slow-blood flow in the neurovascular circulation [43] (Video S7).
The fetal umbilical-portal venous system is complex. High-definition flow imaging (HDFI) has been used to assess the normal anatomy of this system or umbilical-portalsystemic venous shunts. Transverse and sagittal planes are used to examine the fetal umbilical-portal venous system (Video S8a,b). In a recent case report, the authors used HDFI and radiant flow imaging to clearly delineate the aberrant course of the ductus venosus returning to the coronary sinus [44].

3D/4D Ultrasound
Over the years, new 2D modes (such as high-density power imaging), new 3D volume acquisition (such as Corpus callosum mode or matrix probe), and new analysis (such as semiautomated analysis) have been added in 3D/4D ultrasound examinations (Table 1). The use of 3D multiplanar/multislice analysis facilitates the assessment of normal and abnormal structures in standard planes. This can also facilitate the detection of subtle fetal defects [45]. The use of 3D rendered images can help counseling to the women when fetal malformations are found or reassure the at-risk women when normal fetal anatomy is found [45]. 3D/4D US is useful for the assessment of fetal brain, spine, face, heart, and other structures [45,46]. Examples in the assessment of fetal abnormalities a.
Cleft lip and palate: use gray-scale mode, after a 3D volume acquisition, perform multiplanar/multi-slice analysis and rendering techniques to assess the integrity of palate. b.
Short-limbed and short-rib dysplasia: use gray-scale mode, after a 3D volume acquisition with skeletal mode, perform rendering techniques with skeletal mode to examine the long bones and ribs. c.
Agenesis of ductus venosus: use high-density power imaging, after a 3D volume acquisition, perform multi-slice analysis to assess the precordial venous system. d.
Cardiac outflow tract abnormalities: use color flow, after a STIC volume acquisition, perform multiplanar/multi-slice analysis in a cine-loop of cardiac cycle. e. Atrioventricular valve abnormalities: use matrix probe and gray-scale mode, realtime 4D cine-loop analysis to display the coronal view of atrioventricular valve.

3D Neurosonography
In targeted neurosonography, a systematic assessment of the fetal brain is required. Although this assessment can be performed by a 2D ultrasound examination, a perfect midsagittal view may not be achieved at all times, thus affecting a proper assessment. ISUOG recommends using 3D ultrasound examination that can provide images of enhanced resolution by displaying thicker 'slices' of the brain and thus increasing the signal-tobackground noise ratio on all three planes. In addition, multiplanar imaging correlation allows the display of perfectly aligned views on the three orthogonal planes [5]. To avoid shallowing by adjacent skull bones, it is important to acquire a 3D volume in a midsagittal plane through the sagittal suture. If the focus is on the anterior complex, the volume will be obtained from the anterior fontanelle or the anterior part of the sagittal suture [5] (Figure 7a). If the focus is on the posterior fossa and cerebellar vermis, the volume will be obtained from the posterior fontanelle or the posterior part of the sagittal suture with the ultrasound beam being almost perpendicular to the tentorium [47] (Figure 7b). A transvaginal and transabdominal approach is used when the fetal presentation is vertex and breech, respectively. Then, the midlines structures including corpus callosum, brain stem, and cerebellar vermis can be examined by multiplanar and multi-slice analysis [43,48,49]. An accurate measurement of corpus callosum and cerebellar vermis can be achieved. After a 3D volume acquisition of the fetal spine at mid-sagittal plane, a rendered view of the fetal spine can be well displayed with various modes (Figure 8a,b). In addition, the coronal planes at the level of the vertebral bodies and/or posterior arches can be reconstructed on multiplanar analysis [5].

Spatiotemporal Image Correlation
Spatiotemporal Image Correlation (STIC) allows an automatic acquisition of a single 3D volume through slow sweep and subsequent analysis in a looped cine sequency of images in the multiplanar/multi-slice format and a rendered view. This can produce images in a standardized plane while minimizing the operation dependency of the ultrasound examination. The recent advances in gray scale and color Doppler post processing After a 3D volume acquisition of the fetal spine at mid-sagittal plane, a rendered view of the fetal spine can be well displayed with various modes (Figure 8a,b). In addition, the coronal planes at the level of the vertebral bodies and/or posterior arches can be reconstructed on multiplanar analysis [5]. After a 3D volume acquisition of the fetal spine at mid-sagittal plane, a rendered view of the fetal spine can be well displayed with various modes (Figure 8a,b). In addition, the coronal planes at the level of the vertebral bodies and/or posterior arches can be reconstructed on multiplanar analysis [5].

Spatiotemporal Image Correlation
Spatiotemporal Image Correlation (STIC) allows an automatic acquisition of a single 3D volume through slow sweep and subsequent analysis in a looped cine sequency of images in the multiplanar/multi-slice format and a rendered view. This can produce images in a standardized plane while minimizing the operation dependency of the ultrasound examination. The recent advances in gray scale and color Doppler post processing

Spatiotemporal Image Correlation
Spatiotemporal Image Correlation (STIC) allows an automatic acquisition of a single 3D volume through slow sweep and subsequent analysis in a looped cine sequency of images in the multiplanar/multi-slice format and a rendered view. This can produce images in a standardized plane while minimizing the operation dependency of the ultrasound examination. The recent advances in gray scale and color Doppler post processing improves the display of ultrasound images. Using color Doppler with STIC in the glass-body mode can show normal and abnormal anatomy of the fetal heart and major vessels [46] (Figure 9, Video S9). The matrix probe allows the rapid acquisition of an STIC volume, thus reducing the motion artifact and facilitating live 4D display [46]. In addition, the use of the matrix probe allows the simultaneous examination of two orthogonal planes of the fetal heart in the 'biplane mode'. Additional use of image recognition software can help review cardiac structures in the standard planes [46]. The 3D rendered images are useful for counseling to parents. In addition, STIC volume can facilitate interdisciplinary consultation and teleconsultation [42]. improves the display of ultrasound images. Using color Doppler with STIC in the glassbody mode can show normal and abnormal anatomy of the fetal heart and major vessels [46] (Figure 9, Video S9). The matrix probe allows the rapid acquisition of an STIC volume, thus reducing the motion artifact and facilitating live 4D display [46]. In addition, the use of the matrix probe allows the simultaneous examination of two orthogonal planes of the fetal heart in the 'biplane mode'. Additional use of image recognition software can help review cardiac structures in the standard planes [46]. The 3D rendered images are useful for counseling to parents. In addition, STIC volume can facilitate interdisciplinary consultation and teleconsultation [42].

3D Ultrasound Examination of Face, Limbs, and Other Structures
While 2D ultrasound is a key tool for the detection of fetal anomalies, there are some anomalies such as facial clefts, micrognathia, and club foot in which 3D ultrasound may provide additional information or help counseling when such anomaly is suspected [9]. Compared to 2D ultrasound alone, combined approach of 2D and 3D ultrasound with multiplanar/multi-slice analysis can improve the detection or exclusion of cleft palate in fetuses with cleft lip [50] (Figure 10). Although 3D ultrasound is less sensitive for the detection of isolated cleft palate, a recent study showed that an accurate evaluation of palate requires 3D ultrasound examination with volume acquisition in a strictly axial transverse view of the palate [16]. The use of 3D ultrasound multiplanar analysis and 3D rendering view can facilitate the display of mid-sagittal plane of the fetal face and thus improve the accuracy of measurements of the mandible and the detection of micrognathia [51].

3D Ultrasound Examination of Face, Limbs, and Other Structures
While 2D ultrasound is a key tool for the detection of fetal anomalies, there are some anomalies such as facial clefts, micrognathia, and club foot in which 3D ultrasound may provide additional information or help counseling when such anomaly is suspected [9]. Compared to 2D ultrasound alone, combined approach of 2D and 3D ultrasound with multiplanar/multi-slice analysis can improve the detection or exclusion of cleft palate in fetuses with cleft lip [50] (Figure 10). Although 3D ultrasound is less sensitive for the detection of isolated cleft palate, a recent study showed that an accurate evaluation of palate requires 3D ultrasound examination with volume acquisition in a strictly axial transverse view of the palate [16]. The use of 3D ultrasound multiplanar analysis and 3D rendering view can facilitate the display of mid-sagittal plane of the fetal face and thus improve the accuracy of measurements of the mandible and the detection of micrognathia [51].
Three-dimensional (3D) rendering technology with skeletal mode can display skull, vertebrae, ribs, long bones and fingers [52] (Figure 11a,b and Video S10a,b). Prenatal assessment of the ribs and vertebral pattern can be performed by 3D ultrasound with skeletal mode (Figure 8a,b), albeit it is not a routine practice. A review of 39 studies including 75,018 healthy subjects and 6130 subjects with structural or chromosomal anomalies or adverse outcome showed an association between cervical ribs and other structural anomalies including esophageal atresia and anorectal malformation [53]. Abnormalities such as craniosynostosis [26,54], and extra ribs can be shown. Three-dimensional (3D) rendering technology with skeletal mode can display skull, vertebrae, ribs, long bones and fingers [52] (Figure 11a,b and Video S10a,b). Prenatal assessment of the ribs and vertebral pattern can be performed by 3D ultrasound with skeletal mode (Figure 8a,b), albeit it is not a routine practice. A review of 39 studies including 75,018 healthy subjects and 6,130 subjects with structural or chromosomal anomalies or adverse outcome showed an association between cervical ribs and other structural anomalies including esophageal atresia and anorectal malformation [53]. Abnormalities such as craniosynostosis [26,54], and extra ribs can be shown. It is difficult to visualize esophagus on 2D ultrasound examination. The use of 3D ultrasound with multiplanar analysis and Crystal Vue rendering may make the visualization possible [55]. Three-dimensional (3D) volumes are acquired from a midsagittal section of the thorax and upper abdomen with the fetus lying in supine position.
While 2D ultrasound examination with gray scale and color flow is the standard for the antenatal diagnosis of placenta accreta spectrum disorders [22], 3D ultrasound with  Three-dimensional (3D) rendering technology with skeletal mode can display vertebrae, ribs, long bones and fingers [52] (Figure 11a,b and Video S10a,b). Prena sessment of the ribs and vertebral pattern can be performed by 3D ultrasound wit etal mode (Figure 8a,b), albeit it is not a routine practice. A review of 39 studies inc 75,018 healthy subjects and 6,130 subjects with structural or chromosomal anoma adverse outcome showed an association between cervical ribs and other structural alies including esophageal atresia and anorectal malformation [53]. Abnormalities s craniosynostosis [26,54], and extra ribs can be shown. It is difficult to visualize esophagus on 2D ultrasound examination. The use ultrasound with multiplanar analysis and Crystal Vue rendering may make the vis tion possible [55]. Three-dimensional (3D) volumes are acquired from a midsagit tion of the thorax and upper abdomen with the fetus lying in supine position.
While 2D ultrasound examination with gray scale and color flow is the stand the antenatal diagnosis of placenta accreta spectrum disorders [22], 3D ultrasoun It is difficult to visualize esophagus on 2D ultrasound examination. The use of 3D ultrasound with multiplanar analysis and Crystal Vue rendering may make the visualization possible [55]. Three-dimensional (3D) volumes are acquired from a midsagittal section of the thorax and upper abdomen with the fetus lying in supine position.
While 2D ultrasound examination with gray scale and color flow is the standard for the antenatal diagnosis of placenta accreta spectrum disorders [22], 3D ultrasound with power Doppler and multiplanar analysis permits an accurate assessment of the placenta-bladder interface, and the degree of bladder invasion by the placenta [56]. Three-dimensional (3D) rendered images can be used for patient counseling [56].

3D Printing
With advances in 3D ultrasound, the derived ultrasound data can be used for 3D printing of physical models of whole fetuses [57] and the fetal face [58]. A recent trial showed that the use of 3D-printed fetal facial models resulted in greater increases in maternal-fetal attachment in the third trimester than the use of ultrasonography only [58]. Whether this can be translated into better pregnancy outcomes needs further studies. In addition, a 3D-printed spina bifida model can be beneficial for surgical rehearsal prior to a fetoscopic repair [59].
With advances in STIC, the derived data can be used for 3D printing of the fetal heart, which is a fast-moving structure [60]. In a recent case report, the authors found that the 3D model was useful in showing the complex anatomy of fetal transposition of great arteries and in providing prenatal parental counseling [61].
Previously, after acquisition of a 3D/STIC volume dataset, a number of post-processing steps are required to convert it from Cartesian.vol file through segmentation, refinement, and optimization to a STL (Standard Triangle Language) file, the industry standard file type for 3D Printing [60]. These steps take a long time, and whether the final produced STL file is good enough for 3D printing is not certain before processing. With recent advances in ultrasound technology, a 3D/STIC volume dataset can be directly exported from the ultrasound machine as an STL file that is ready for viewing on a personal computer using common software as well as for 3D printing (Figure 12).

3D Printing
With advances in 3D ultrasound, the derived ultrasound data can be used for 3D printing of physical models of whole fetuses [57] and the fetal face [58]. A recent tria showed that the use of 3D-printed fetal facial models resulted in greater increases in ma ternal-fetal attachment in the third trimester than the use of ultrasonography only [58 Whether this can be translated into better pregnancy outcomes needs further studies. I addition, a 3D-printed spina bifida model can be beneficial for surgical rehearsal prior t a fetoscopic repair [59].
With advances in STIC, the derived data can be used for 3D printing of the fetal hear which is a fast-moving structure [60]. In a recent case report, the authors found that th 3D model was useful in showing the complex anatomy of fetal transposition of great ar teries and in providing prenatal parental counseling [61].
Previously, after acquisition of a 3D/STIC volume dataset, a number of post-pro cessing steps are required to convert it from Cartesian.vol file through segmentation, re finement, and optimization to a STL (Standard Triangle Language) file, the industr standard file type for 3D Printing [60]. These steps take a long time, and whether the fina produced STL file is good enough for 3D printing is not certain before processing. Wit recent advances in ultrasound technology, a 3D/STIC volume dataset can be directly ex ported from the ultrasound machine as an STL file that is ready for viewing on a persona computer using common software as well as for 3D printing (Figure 12).

FetalHQ
FetalHQ, a novel heart and vascular analysis software, can allow assessment of th fetal heart shape, size, and contractibility by using speckle tracking to analyze the motio of multiple points of the fetal heart [62] (Figure 13). The global sphericity index (SI) is simple measurement of cardiac contractility, and it is equal to (end-diastolic mid-basal apical length)/transverse length [63]. For 24-segment sphericity index, SI is computed fo each of the 24 end-diastolic transverse segments, which are distributed from the base t the apex of each ventricle, as well as the end-diastolic mid-basal-apical length [62].

FetalHQ
FetalHQ, a novel heart and vascular analysis software, can allow assessment of the fetal heart shape, size, and contractibility by using speckle tracking to analyze the motion of multiple points of the fetal heart [62] (Figure 13). The global sphericity index (SI) is a simple measurement of cardiac contractility, and it is equal to (end-diastolic mid-basal-apical length)/transverse length [63]. For 24-segment sphericity index, SI is computed for each of the 24 end-diastolic transverse segments, which are distributed from the base to the apex of each ventricle, as well as the end-diastolic mid-basal-apical length [62].
This 24-segment sphericity index is a comprehensive method to assess the shape of ventricular chambers [62]. The SI for each segment was independent of gestational age and fetal biometry. The SI of the right ventricle was lower than that of the left ventricle for segments 1-18. This index can be used when discordance between the size of the atrial and/or ventricular cardiac chambers is found. Abnormal SI values are found in the fetuses with cardiac abnormalities such as coarctation of aorta, pulmonary stenosis, and fetal growth restriction [62]. Abnormal SI values are associated with increased risk of perinatal complications and childhood and/or adult cardiovascular disease [64]. Figure 13. FetalHQ assessment of the fetal heart shape, size, and contractibility by using speckle tracking to analyze the motion of multiple points of the fetal heart at 20 weeks' gestation. This 24-segment sphericity index is a comprehensive method to assess the shape of ventricular chambers [62]. The SI for each segment was independent of gestational age and fetal biometry. The SI of the right ventricle was lower than that of the left ventricle for segments 1-18. This index can be used when discordance between the size of the atrial and/or ventricular cardiac chambers is found. Abnormal SI values are found in the fetuses with cardiac abnormalities such as coarctation of aorta, pulmonary stenosis, and fetal growth restriction [62]. Abnormal SI values are associated with increased risk of perinatal complications and childhood and/or adult cardiovascular disease [64].
While the initial results are promising, a recent review of 23 studies showed conflicting results concerning the development of strain and strain rate during gestation [65]. Large longitudinal cohort studies with a standard protocol are needed to obtain reference values for fetal cardiac deformation in uncomplicated pregnancies [65]. A recent systematic review also showed heterogeneous results concerning gestational age and Doppler profiles. Large prospective longitudinal cohort studies are required to assess the clinical significance of deformation measurements of the fetal heart in growth restricted fetuses and normal fetuses [66].

Artificial Intelligence
Machine learning, in particular deep learning, allows ultrasound image recognition and thus facilitates the automatic identification and measurement of fetal biometry [67]. It is a branch of artificial intelligence (AI). In obstetric ultrasonography, the automation of measurements of fetal biometry is a potentially useful tool to increase the reliability and reproducibility of measurements as compared to manual measurements [68]. In addition, it can reduce scanning time [68] and work-related fatigue and musculoskeletal disorders [69].
With automatic image recognition technology applied on a frozen 2D ultrasound image, auto measurement of fetal biometry including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) becomes feasible. A study showed a success rate of 91.43% and 100% for auto measurement of HC and BPD, respectively [67]. Although the inaccuracy for the plane acceptance check for head parameters was 12.9% [67], such inaccuracy can be corrected by fine-tuning of the caliper placement manually. In another study, manual adjustment of caliper position was not required in about two-thirds of cases for HC and FL measurements, but it was required in more than 80% for the measurement of AC [68]. Auto measuring AC is more difficult than measuring HC because of the low contrast between the abdomen and surrounding tissues and the large variability in abdominal shape and appearance [68]. The accuracy of the auto Figure 13. FetalHQ assessment of the fetal heart shape, size, and contractibility by using speckle tracking to analyze the motion of multiple points of the fetal heart at 20 weeks' gestation.
While the initial results are promising, a recent review of 23 studies showed conflicting results concerning the development of strain and strain rate during gestation [65]. Large longitudinal cohort studies with a standard protocol are needed to obtain reference values for fetal cardiac deformation in uncomplicated pregnancies [65]. A recent systematic review also showed heterogeneous results concerning gestational age and Doppler profiles. Large prospective longitudinal cohort studies are required to assess the clinical significance of deformation measurements of the fetal heart in growth restricted fetuses and normal fetuses [66].

Artificial Intelligence
Machine learning, in particular deep learning, allows ultrasound image recognition and thus facilitates the automatic identification and measurement of fetal biometry [67]. It is a branch of artificial intelligence (AI). In obstetric ultrasonography, the automation of measurements of fetal biometry is a potentially useful tool to increase the reliability and reproducibility of measurements as compared to manual measurements [68]. In addition, it can reduce scanning time [68] and work-related fatigue and musculoskeletal disorders [69].
With automatic image recognition technology applied on a frozen 2D ultrasound image, auto measurement of fetal biometry including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) becomes feasible. A study showed a success rate of 91.43% and 100% for auto measurement of HC and BPD, respectively [67]. Although the inaccuracy for the plane acceptance check for head parameters was 12.9% [67], such inaccuracy can be corrected by fine-tuning of the caliper placement manually. In another study, manual adjustment of caliper position was not required in about two-thirds of cases for HC and FL measurements, but it was required in more than 80% for the measurement of AC [68]. Auto measuring AC is more difficult than measuring HC because of the low contrast between the abdomen and surrounding tissues and the large variability in abdominal shape and appearance [68]. The accuracy of the auto measurement of HC, AC, and FL was high, and it compared well with previously published manual-to-manual agreement, but the auto measurements had a tendency to underestimate biometry, which requires further improvements in the algorithm [68].
With automatic image recognition technology applied on an acquired 3D ultrasound volume of the fetal head from the BPD plane, SonoCNS allows auto measurement of fetal biometry including BPD, HC, atrium of the posterior horn of the lateral ventricle (Vp), transcerebellar diameter (TCD), and cisterna magnum (CM) [70] (Figure 14). A recent study showed that this 3D automated technology reliably identified and measured BPD and HC but was less so for TCD, CM, and Vp [70]. Further optimization of this automated technology is required.
lished manual-to-manual agreement, but the auto measurements had a tendency to underestimate biometry, which requires further improvements in the algorithm [68].
With automatic image recognition technology applied on an acquired 3D ultrasound volume of the fetal head from the BPD plane, SonoCNS allows auto measurement of fetal biometry including BPD, HC, atrium of the posterior horn of the lateral ventricle (Vp), transcerebellar diameter (TCD), and cisterna magnum (CM) [70] (Figure 14). A recent study showed that this 3D automated technology reliably identified and measured BPD and HC but was less so for TCD, CM, and Vp [70]. Further optimization of this automated technology is required. Fetal Intelligent Navigation Echocardiography (FINE) applied on a STIC volume using "intelligent navigation" technology allows the automatic display of nine standard fetal echocardiography views [71]. This can simplify fetal cardiac examinations, reduce operator dependency, and help detect congenital heart defects [71].
During a real-time 2D morphology scan, identifying and interpreting fetal standard scan planes are highly complex tasks. With automatic image processing technology [46,70], these tasks can be assisted by providing feedback or guidance to an ultrasound operator on whether a correct standard scan plane of fetal anatomy is obtained, whether all parts of anatomy are checked, and whether unusual findings on a standard plane are identified [72]. The operator can use this technology as a second pass or confirmation to improve diagnostic accuracy [70]. This can also allow audit and quality improvement [73].
Based on deep learning, image segmentation is an image processing method that can automatically recognize the location and size of an object in pixels. However, accurate segmentation of most anatomical structures in medical ultrasound is limited by the low contrast between the target and background of the images [74]. To improve the segmentation performance of the thoracic wall in fetal ultrasound videos, a novel model-agnostic method using deep learning techniques in processing time-series information of ultrasound videos and the shape of the thoracic wall was proposed [75]. Accurate segmentation can assist ultrasonographers with identifying the thoracic area and its orientation, and it has the potential to build AI-based diagnostic support models to assess four-chamber view [75].
There are emerging studies on the application of artificial intelligence in obstetric scan. It is feasible to use 3D ultrasound to automatic measure thymic volume [76]. Twodimensional (2D) placental sonographic images can be screened for lacunae, which is a Fetal Intelligent Navigation Echocardiography (FINE) applied on a STIC volume using "intelligent navigation" technology allows the automatic display of nine standard fetal echocardiography views [71]. This can simplify fetal cardiac examinations, reduce operator dependency, and help detect congenital heart defects [71].
During a real-time 2D morphology scan, identifying and interpreting fetal standard scan planes are highly complex tasks. With automatic image processing technology [46,70], these tasks can be assisted by providing feedback or guidance to an ultrasound operator on whether a correct standard scan plane of fetal anatomy is obtained, whether all parts of anatomy are checked, and whether unusual findings on a standard plane are identified [72]. The operator can use this technology as a second pass or confirmation to improve diagnostic accuracy [70]. This can also allow audit and quality improvement [73].
Based on deep learning, image segmentation is an image processing method that can automatically recognize the location and size of an object in pixels. However, accurate segmentation of most anatomical structures in medical ultrasound is limited by the low contrast between the target and background of the images [74]. To improve the segmentation performance of the thoracic wall in fetal ultrasound videos, a novel model-agnostic method using deep learning techniques in processing time-series information of ultrasound videos and the shape of the thoracic wall was proposed [75]. Accurate segmentation can assist ultrasonographers with identifying the thoracic area and its orientation, and it has the potential to build AI-based diagnostic support models to assess four-chamber view [75].
There are emerging studies on the application of artificial intelligence in obstetric scan. It is feasible to use 3D ultrasound to automatic measure thymic volume [76]. Twodimensional (2D) placental sonographic images can be screened for lacunae, which is a feature of PAS [77]. Preliminary results are encouraging. Further improvement of algorithm and technology are required prior to using AI applications in clinical practice.

Conclusions
The use of high-resolution ultrasonography can facilitate detailed diagnostic ultrasonography, in particular, fetal echocardiography and targeted neurosonography, in at-risk pregnancies, as suggested by the recent guidelines. The use of radiant flow can improve the display, especially in complex cardiac or vascular structures. The use of 3D/4D ul-trasound may help in the prenatal diagnosis and counseling of some fetal abnormalities. Select use of linear transducer may enhance the diagnostic capabilities of some superficial anomalies. Speckle tracking of the fetal heart can allow assessment of fetal heart shape, size and contractibility, and further studies are required to assess its clinical effectiveness. At present, automated tools for simple task such as measurement of fetal growth biometry are a good assistant to routine ultrasonography. Further refinement of automated algorithm is required, especially for complex tasks, to improve the workflow.
Supplementary Materials: The following are available online at https://www.mdpi.com/article/ 10.3390/diagnostics11071217/s1. Video S1. High-resolution ultrasonography of the fetal heart at 20 weeks' gestation showing four-chamber view with two pulmonary veins connecting to the left atrium at a high frame rate. Video S2. High-resolution ultrasonography of the fetal brain at 20 weeks' gestation: (a) mid-sagittal view showing corpus callosum, thalamus, brain stem and cerebellar vermis,