Fetal "gallstones" are still an unsolved mystery. Case series.

BACKGROUND: Echogenic content in the fetal gallbladder is rather an incidental finding during third-trimester ultrasonography. The etiology, clinical course, and prognosis of this condition are still unclear. We highlight the demographic, clinical and ultrasound characteristics of our patients with echogenic content in the fetal gallbladder. METHODS: This is a retrospective single-center study conducted at the University of Medicine and Pharmacy Cluj-Napoca, Romania, between March 2022 and April 2023. All pregnant patients who were admitted to the hospital and had echogenic content in the fetal gallbladder detected by ultrasound were identified. The clinical and ultrasonography parameters were obtained from the databases of the ultrasound units and the medical records of the patients. RESULTS: Four patients were found to have echogenic content in the fetal gallbladder. The mean maternal age at diagnosis was 27.5 years (range 25-31). All patients had singleton pregnancies. The mean gestational age at diagnosis was 36.5 weeks (range 35-40). In all cases, the predominant aspect of echogenic content on ultrasound was multiple hyperechogenic foci; additionally, in one case, sludge was also observed. The mean maximal length of the hyperechogenic foci was 3.375 mm (range 1.6-5.4). All fetuses were delivered at full term, either vaginally or by cesarean section. The mean weight at birth was 3082.5 g (range 2800-3450). In all four cases, the EC disappeared spontaneously at birth. Neither of the four newborns displayed digestive symptoms or complications during the follow-up. CONCLUSION: The EC is still a medical mystery since little is known about its etiology and long-term outcome. Many cases are likely to be undetected until after birth; therefore, fetal gallbladder examination should be included in the US routine. The condition appears to be benign, and usually, it improves naturally after birth. Consecutively, asymptomatic newborns with EC can be managed through a wait-and-see approach.

Neonatal Hemochromatosis: Systematic Review of Prenatal Ultrasound Findings-Is There a Place for MRI in the Diagnostic Process?

Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.

Ultrasound Placental Remodeling Patterns and Pathology Characteristics in Patients with History of Mild SARS-CoV-2 Infection during Pregnancy.

Introduction: This research aims to describe a progressive pattern of ultrasound placental remodeling in patients with a history of SARS-CoV-2 infection during pregnancy. Materials and Methods: This was a longitudinal, cohort study which enrolled 23 pregnant women with a history of former mild SARS-CoV-2 infection during the current pregnancy. Four obstetricians analyzed placental ultrasound images from different gestational ages following COVID infection and identified the presence and degree of remodeling. We assessed the inter-rater agreement and the interclass correlation coefficients. Pathology workup included placental biometry, macroscopic and microscopic examination. Results: Serial ultrasound evaluation of the placental morphology revealed a progressive pattern of placental remodeling starting from 30-32 weeks of gestation towards term, occurring approximately 8-10 weeks after the SARS-CoV-2 infection. Placental changes-the "starry sky" appearance and the "white line" along the basal plate-were identified in all cases. Most placentas presented normal subchorionic perivillous fibrin depositions and focal stem villi perivillous fibrin deposits. Focal calcifications were described in only 13% of the cases. Conclusions: We identified two ultrasound signs of placental remodeling as potential markers of placental viral shedding following mild SARS-CoV-2. The most likely pathology correspondence for the imaging aspect is perivillous and, respectively, massive subchorionic fibrin deposits identified in most cases.

Echogenic Content in the Fetal Gallbladder: Systematic Review of Ultrasound Features and Clinical Outcome.

It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of 100 database entries identified in PubMed, EMBASE, and ICTRP reviews, we selected 34 studies in which we investigated the ultrasound features and outcome of this condition. There were 226 fetuses with gallbladder echogenic content identified. Seventy-two fetuses were found to have biliary sludge; thirty cases had a single hyperechogenic focus, and one hundred fetuses had multiple foci in the gallbladder. There were 16 cases of distal shadowing, 37 fetuses with comet tail and twinkling, and 26 cases with no acoustic artifacts. Nine cases of spontaneous resolution before birth have been documented; nine fetuses exhibited no echogenic content at birth, and 138 cases of resolution of echogenic content within the first year of life have been described. Typically, the condition resolves spontaneously during the postnatal period. After adequately reassuring the parents, the patients should be monitored for spontaneous resolution; medical or surgical intervention is not indicated. Asymptomatic patients can be managed with a wait-and-see strategy.

Fetal cardiac rhabdomyomas as a sonographic sign of tuberous sclerosis complex - a diagnosis not to be missed. A pictorial essay.

Fetal cardiac rhabdomyomas should trigger the awareness of a potential coexisting tuberous sclerosis complex that can lead to a poor neurological outcome. This condition is not only uncommon but can be easily unrecognized prenatally in the absence of a meticulous neurosonogram and MRI. We emphasize that careful consideration of all prenatal facilities is required to confirm the diagnosis of tuberous sclerosis complex as early as possible during pregnancy.

First trimester sonographic diagnosis of limb-body wall defect associating both cephalic and thoraco-abdominal defects - a case report and literature update.

We present the first trimester prenatal ultrasonography and pathological assessment of a case diagnosed with limb-body wall complex (LBWC) presenting both exenchephaly and a complex thoraco-abdominal wall defect. Ectopia cordis is demonstrated with a movie showing the heart beating outside the body of the fetus after its expulsion. Also, we discuss the pathogenesis and possible etiology of LBWC and associated malformations and we provide an update of the literature of this very rare anomaly.

Early development of human ganglionic eminences assessed in vitro by using 7.04 Tesla micro-MRI - a pilot study.

BACKGROUND AND AIMS: Ganglionic eminences are temporary structures which appear during the 5th week post-fertilization on the floor of telencephalic vesicles and disappear until the 35th week of gestation. The aim of this descriptive study of morphological research is to depict the ganglionic eminences within the embryonic and early fetal brains by using micro-MRI. METHODS: Six human embryos and fetuses ranging from 21 mm crown-rump length CRL (9 gestational week GW) to 85 mm CRL (14 GW) were examined in vitro by micro-MRI. The investigation was performed with a Bruker BioSpec 70/16USR scanner (Bruker BioSpin MRI GmbH, Ettlingen, Germany) operating at 7.04 Tesla. RESULTS: We describe the morphological characteristics of the ganglionic eminences at different gestational ages. The acquisition parameters were modified for each subject in order to obtain an increased spatial resolution. The remarkable spatial resolution of 27 µm/voxel allows visualization of millimetric structures of the developing brain on high quality micro-MR images. CONCLUSION: In our study we give the description of the ganglionic eminences within the embryonic and early fetal brains by using micro-MRI, which, to the best of our knowledge, have not been previously documented in literature. Micro-MRI provides accurate images, which are comparable with the histological slices.

Potential clinical benefits and limitations of fetal virtopsy using high-field MRI at 7 Tesla versus stereomicroscopic autopsy to assess first trimester fetuses.

OBJECTIVE: The aim of this study was to establish the diagnostic accuracy of high-field magnetic resonance imaging (MRI) at 7 Tesla (T) compared with that of stereomicroscopic autopsy for assessing first trimester fetuses. METHODS: Nine consecutive cases of first trimester fetuses resulting from spontaneous and therapeutic pregnancy termination were considered. The cases were divided into two groups according to gestational age: the Embryo Group with cases of nine to 10 gestational weeks (GWs) and the Fetus Group with cases of 13 GWs. The first group was scanned using three-dimensional fast imaging with steady state precession (3D FISP), and the second group was scanned using a two-dimensional (2D) turbo spin-echo high-resolution T2-weighted imaging (T2 WI) protocol. A radiologist and two embryologists interpreted the images. All cases were evaluated by invasive autopsy, with pathologist blinded to the imaging results. In total, the database included 270 items for evaluation (9 cases × 30 structures/case). RESULTS: The global agreement between fetal high-field virtopsy and microscopic or stereomicroscopic autopsy was evaluated using 225 evaluation items visible by both methods. Overall, using microscopic examination and stereomicroscopic autopsy as the gold standard, fetal high-field virtopsy had a sensitivity of 94.6% [95% CI, 87.2-98.3] and a specificity of 97.6% [95% CI, 95-98.8]. The positive predictive value (PPV) was 93% [95% CI, 85.7-96.6], and the negative predictive value (NPV) was 98.2% [95% CI, 95.7-99.4]. Cohen kappa coefficient of agreement was k = 0.92 [95% CI, 0.82-0.97], and the McNemar test showed p = 1.00. CONCLUSIONS: Virtual autopsy using high-field MRI at 7 T can be considered a safe alternative approach to stereomicroscopic autopsy for the assessment of fetal structural anomalies at the end of the first trimester of pregnancy.

Transvaginal three-dimensional sonographic assessment of the embryonic brain: a pilot study.

AIMS: A very good knowledge of human embryology is mandatory not only for the correct sonographic assessment of the developing brain, but also for better understanding the origins of congenital anomalies involving the central nervous system. 3D transvaginal sonography may be an effective technique for imaging the developing brain. The aims of this explorative study are to demonstrate the feasibility of imaging the embryonic brain between 7 and 10 weeks of gestation for clinical studies by using a 3D high-frequency vaginal ultrasound transducer and to provide a reference for the morphology of the brain in the embryonic period. MATERIALS AND METHODS: Four embryos of 9 mm, 17 mm, 23 mm and 31 mm crown-rump length respectively were assessed in vivo by transvaginal sonography. We gave a special attention to the embryonic brain. All patients were examined with a Voluson E10, BT 15 ultrasound scanner (GE Healthcare, Zipf, Austria), using a high-frequency 6-12 MHz/ 256-element 3D/4D transvaginal transducer. Three-dimensional sonography was performed routinely as the patients were scanned. The multiplanar display was used after selecting the best volume. The Omni view® software was used for digitally slicing the selected volumes. RESULTS: We describe the morphological details of the developing brains of four embryos ranging from 7 to 10 gestational weeks. In the human embryo 9 mm CRL the hypoechogenic cavities of the three primary vesicles (prosencephalon, mesencephalon, rhombencephalon) could be observed on a sagittal section. In the human embryo 17 mm CRL the prosencephalon was divided into the median diencephalon and two telencephalic vesicles, which were partially separated by the falx cerebri. In the human embryo 23 mm CRL the cerebral hemispheres developed and they were completely separated by the falx cerebri. The choroid plexus was evident inside the lateral ventricles and the fourth ventricle. In the human embryo 31 mm CRL the ventral thalamus was evident, and the ganglionic eminence, as the precursor of the basal ganglia, was well seen on the floor of the cerebral hemispheres. CONCLUSIONS: Studies of embryology are still needed for a complete understanding of the developing brain. 3D sonography using a high-frequency vaginal ultrasound transducer is feasible for imaging the embryonic brain with an acceptable quality for clinical studies.

Ganglionic eminence within the early developing brain visualized by 3D transvaginal ultrasound.

AIM: Early diagnosis of cerebral congenital anomalies requires a profound knowledge of the anatomy of the developing human brain. The ganglionic eminences (GE) are crucial structures of the brain, giving rise mostly to the basal nuclei. The aim of this explorative study is to assess the GE within the embryonic and early fetal brain by using 3D transvaginal US. MATERIAL AND METHODS: From March 2015 to May 2015, a total of 18 singleton non-malformed embryos and fetuses at 9-13 weeks of gestation were assesed in vivo by transvaginal ultrasound using a Voluson E10, BT 15 scanner (GE Healthcare, Zipf, Austria). The 3D sonography was performed routinely as the subjects were scanned. Inter-observer agreement (concordance) was calculated using the Cohen's kappa statistics. RESULTS: At 9 gestational weeks, no GE was identified. At 10 gestational weeks the GE were identified as mere thickenings in the lateral wall of the cerebral hemispheres, well depicted by 3D transvaginal ultrasound using the HDlive rendering mode and the OmniView® software. Starting with 11 gestational weeks the GE are evident. The results of inter-observer agreement for ganglionic eminences identification were as follows: observed agreement Po=0.94, expected agreement Pe=0.76, kappa coefficient=0.83, which means a very good agreement between the observers. CONCLUSIONS: The GE can be clearly visualized by 3D transvaginal sonography, and especially by HDlive rendering mode. This method has become the "golden standard" for in vivo morphological studies of the embryonic and early fetal brain.