Diagnosis of fetal cortical abnormalities by new reference charts for assessment of sylvian fissure biometry.

OBJECTIVE: To develop novel fetal reference ranges for the characterization of the normal appearance of the Sylvian fissures (SF) along gestation and to apply them to fetuses with cortical abnormalities affecting the SF. METHODS: In this cross-sectional study, we used three-dimensional sonographic multiplanar reformatting (3D-MPR) to examine the fetal SF. Normal development was assessed in the second and third trimesters. SF parameters were evaluated in predefined axial and coronal planes: insular height and length, SF depth, and the extent of the coverage of the insula by the frontal and temporal lobes. Intra-observer variability and inter-rater reliability for the studied parameters were evaluated. The new reference charts were applied to 19 fetuses with cortical abnormalities involving the SF who had appropriate sonographic volumes for 3D-MPR analysis. Their diagnoses were confirmed by autopsy, fetal or postnatal MRI, genetic findings related to cortical malformations, or an abnormal cortical imaging pattern with similar MRI findings in an affected sibling. We applied the two previously published references for the evaluation of fetal SF development to these cases and compared the ability of the references to correctly detect SF abnormalities. RESULTS: The study included 189 fetuses of low-risk singleton pregnancies between 24 and 34 gestational weeks. The insular length or height increased with gestational age in the axial and coronal planes with adjusted R2  = 0.621, p < 0.0001 and R2  = 0.384, p < 0.0001, respectively. The SF depth also increased with gestational age in the axial and coronal planes with adjusted R2  = 0.695, p < 0.0001 and R2  = 0.219, p = 0.008, respectively. The extent of the coverage of the insula by the frontal and temporal lobes in the coronal plane increased with gestational age (adjusted R2  = 0.627, p < 0.0001 and R2  = 0.589, p < 0.0001, respectively). The interclass correlation coefficients of the intra- and inter-rater reliability of the studied parameters ranged between 0.71 and 0.97. The cortical anomalies in the 19 fetuses were polymicrogyria (7), simplified gyral pattern (3), dysgyria (3), lissencephaly (2), cortical malformation related to tubulinopathy (1), brain atrophy (1), cortical dysplasia (1), and cobblestone malformation (1). Three of the fetuses had multiple cortical anomalies. In 17 of 19 (89%) cases, at least one of our 6 SF parameters was found to be out of the normal range. In the coronal plane, SF height and depth were measured below 2SD in 9 (47%) and 4 (21%) cases, respectively. In the axial plane, SF length and depth were out of the normal ranges in six (31.5%) and four (21%), correspondingly. In the coronal plane, the opercular coverage by the frontal and temporal lobes was below 2 SD in 10 (52%) and 11 (57%), respectively. The scoring of the SF operculization by Quarello et al. was abnormal in 8 cases (42%). The measurement of the SF angle according to Poon et al. was abnormal in 14 cases (74%). CONCLUSIONS: The fetal SF is a complex developing structure that can be reliably characterized by sonographic parameters. One abnormal parameter is sufficient to raise the suspicion of SF malformation. Our new SF parameters might facilitate the detection of prenatal cortical abnormalities affecting the SF.

A New Insight on Exophytic Serous Borderline Adnexal Tumors: Specific Sonographic Features.

OBJECTIVES: To characterize and compare the sonographic features of exophytic serous borderline ovarian tumors (ESBOT) with those of high-grade serous carcinoma of the ovary (HGSC). METHODS: Seven patients with histological diagnosis of ESBOT diagnosed between 2011 and 2019 and 10 consecutive cases of HGSC detected during 2019, both depicting an exophytic growth pattern, were identified retrospectively. The sonographic imaging of the masses was reassessed and characterized according to the International Ovarian Tumor Analysis terms. RESULTS: A unilateral irregular solid adnexal mass was demonstrated in all patients with ESBOT. The mass typically wrapped an apparently normal ovary, with a clear demarcation line depicted between them and it contained tiny cystic inclusions and calcifications. On color Doppler study of all the ESBOT cases, a unique vascular pattern could be demonstrated: an intratumoral vascular bundle originating from the ovarian vessels and supplying a rich radial blood flow to the tumor periphery. These characteristic morphological and color Doppler features could not be observed in any of the HGSC cases (P < .001). In 42.8% of the patients with ESBOT, additional unilocular-solid components (ipsilateral or contralateral) could be detected, whereas all the HGSC patients presented with a multilocular-solid tumor morphology (P < .001). The interface of the external mass border with the adjacent pelvic walls was regular in all the cases with ESBOT, whereas in 80% of HGSC patients, it was irregular, suggesting invasiveness (P = .002). CONCLUSIONS: ESBOT can mimic HGSC. Our results suggest that ESBOT has specific B-mode and color Doppler features, enabling differentiation from HGSC and planning appropriate intervention.

Prenatal sonographic features of triploidy at 12-16 weeks.

OBJECTIVE: The purpose of our study was to describe the sonographic appearance of triploidy in early pregnancy. METHODS: We report the sonographic characteristics of a cohort of fetal triploid cases detected at targeted ultrasonographic vaginal examinations between 12 and 16 weeks of gestation from 2008 to 2014. Indications for fetal karyotype following ultrasound were maternal request, advanced maternal age, increased nuchal translucency, and/or fetal abnormalities. RESULTS: Triploidy was detected in 25 cases during the 6 years of the study period with an estimated incidence of ~1 in 5000 pregnancies. Four cases had molar changes in the placenta. Among the remaining 21 cases, a consistent sonographic pattern was noted, which included the combination of asymmetric growth restriction with abdominal circumference lagging 2 weeks behind head circumference in 21/21, oligohydramnios in 20/21, abnormal posterior fossa or enlarged fourth ventricle in 20/21, and absent gall bladder in 17/21. Other findings present in more than 50% of cases included cardiac (70%) and renal (55%) abnormalities, clenched hands (55%), and hypoplastic lungs (67%). CONCLUSION: Fetal triploidy can manifest at 12-16 weeks with molar changes in the placenta or with a cluster of unusual sonographic findings whose presence should prompt appropriate testing for diagnosis in early pregnancy. © 2016 John Wiley & Sons, Ltd.

Effect of B-mode optimization techniques on fetal bowel echogenicity using computerized image analysis.

OBJECTIVES: The purpose of this study was to provide and compare measurable parameters for normal fetal bowel echogenicity under predefined B-mode scanning presets. METHODS: Forty healthy fetuses underwent 14- to 17-week ultrasound scans, and 40 underwent 21- to 25-week scans. Sagittal, coronal, and axial fetal abdominal images were tested using predefined B-mode presets. The presets differed from fundamental imaging by isolated activation of harmonic imaging, compound resolution imaging, speckle reduction imaging, focus and frequency composite imaging, and coded excitation imaging features. A transabdominal probe was used in all fetuses, and transvaginal images were added for the 14- to 17-week scans. The images were studied with custom-developed software, which provided a grayscale analysis of the pixels in the region of interest within the image. The mean brightness of the pixels from the fetal bowel area was calculated. RESULTS: The 14- to 17-week transabdominal scans showed significantly higher mean brightness on harmonic imaging compared to fundamental imaging (P < .01). Activation of coded excitation and compound resolution imaging in these scans resulted in a significant decrease in the mean brightness compared to fundamental imaging. Mean bowel brightness values on the 21- to 25-week transabdominal scans did not differ significantly with the use of the different imaging presets compared to fundamental imaging. CONCLUSIONS: Transabdominal harmonic imaging in the early second trimester may significantly increase the mean brightness of the fetal bowel tissue. Contrarily, compound resolution imaging and coded excitation imaging produce the opposite effect on bowel echogenicity.

Sonography of the fetal cochlea in the early second trimester of pregnancy.

OBJECTIVES: To examine the feasibility of imaging the fetal cochlea in the early second trimester. METHODS: This study included 42 healthy fetuses of low-risk pregnancies between 14 and 16 weeks. The coronal head sections via sagittal and lateral acoustic windows were used for cochlear visualization. The coronal plane was directed across the thalamus, oriented to the petrous part of the temporal bones. All fetuses were examined by 2-dimensional(2D) transvaginal sonography. Transabdominal scans were added in 11 fetuses at 16 weeks. Three-dimensional (3D) multiplanar reconstruction was used for coronal plane reformatting in cases with inappropriate head positioning for 2D scanning. RESULTS: Because of temporal bone hypomineralization in the early second trimester, sonographic depiction of the cochlear labyrinth was possible. On coronal imaging, the cochleas showed ringlike echogenic borders containing hypoechoic liquid content. The cochlear modiolus appeared as a central echogenic round spot ("cochlear target sign"). The cochleas were observed caudad to the temporal lobes, separated by the clivus. Shifting of the coronal plane showed progressive coiling of the basal cochlear turn toward the second turn ("cochlear whirlpool sign"). Two-dimensional transvaginal scanning showed at least 1 cochlea in 79% (33 of 42) of the cases. Adding 3D multiplanar reconstruction, at least 1 cochlear target sign was observed in 83% (35 of 42). The cochlear whirlpool sign on at least one side was shown in 57% (24 of 42). The maximal cochlear diameter was measured in fetuses with clear cochlear margin visualization. In this subgroup, the mean gestational age ± SD was 15.8 ± 0.5 weeks, and the mean maximal cochlear diameter was 6.4 ± 0.8 mm. CONCLUSIONS: Prenatal sonographic inner ear depiction was previously considered impossible. Using a unique time window in the early second trimester, we achieved feasible fetal cochlear imaging.

Variations of the origin of renal arteries in the fetus identified on power Doppler and 3D sonography.

PURPOSE: To investigate anatomic variations of renal arteries (RAs) using 2-dimensional (2D)/3D power Doppler sonography (PDUS) in normal fetuses and in fetuses with renal anomalies. METHODS: The origin, direction, and distribution of RAs were studied in 120 fetuses without renal malformations using 2D/3D PDUS. Studies were performed between 14 and 17 weeks of gestation age on 64 male and 56 female fetuses. PDUS of the RAs was also performed in 12 fetuses with renal anomalies. RESULTS: In 117/120 fetuses, a single RA was found to originate from each side of the abdominal aorta. The origin of the right RA from the abdominal aorta was superior to, at the same level as, and inferior to that of the left RA in 47% (55/117), 25.5% (30/117), and 27.5% (32/117) of the cases, respectively. An accessory right RA was found in 3 cases. Bifurcation of the right RA was found in 2 cases. There were no variations of the origin of renal vessels in 69% of the cases (83/120), whereas the remaining 31% (37/120) had 1 or several variation patterns. Variations in renal vessels were found in 8 of the 12 fetuses with renal malformations: accessory artery in 3 cases, origin of the right RA from the iliac artery in horseshoe kidney and in 2 cases with pelvic kidney, and bifurcation in 2 of the fetuses with double collecting system. CONCLUSIONS: Variations in origin and distribution of fetal RAs are frequently observed in normal pregnancies. The majority of renal malformations are associated with such vascular variations.

Expectant management of pregnancy-related high-velocity uterine arteriovenous shunt diagnosed after abortion.

OBJECTIVE: To assess sonographic and clinical outcome in women with pregnancy-related uterine arteriovenous malformations (AVMs) diagnosed after abortion. METHOD: Twelve patients diagnosed as having AVMs after abortion were followed-up until resolution of the lesions. RESULTS: The 9 asymptomatic patients were managed expectantly for 4 to 10 weeks without further complications. None of the 12 required aggressive interventions such as transcatheter arterial embolization, and 6 had uncomplicated pregnancies after resolution of the lesions. CONCLUSION: Expectant management is an option in many women with pregnancy-related uterine AVMs.

The oral absorption of phospholipid prodrugs: in vivo and in vitro mechanistic investigation of trafficking of a lecithin-valproic acid conjugate following oral administration.

The purpose of this study was to evaluate the oral absorption characteristics of a phospholipid-drug conjugate, comprising direct conjugation between the lecithin and the drug moiety through the sn-2 position. We investigated the mechanisms involved with the trafficking of this conjugate following oral administration in the gastrointestinal (GI) lumen, within the enterocyte and further. A phospholipid-valproic acid conjugate (DP-VPA) was utilized as a model molecule. The oral absorption of this conjugate in rats was investigated following administration in long (LCT) vs. medium (MCT) chain triglyceride formulations, and in the postprandial vs. fasted state. Oral administration within the LCT solution caused more than a 3-fold increase in DP-VPA bioavailability in comparison to the MCT solution. Moreover, a significant food effect was evident for DP-VPA. Hence, we evaluated the lymphatic transport of DP-VPA in mesenteric lymph duct cannulated freely moving rats. Sixty percent of the absorbed DP-VPA was associated with lymphatic transport. Similar DP-VPA absorption was obtained in secretory type II PLA(2) knockout mice (C57BL/6) and in control mice (BALB/c). Moreover, nil DP-VPA degradation in serum and very low (4.8%) degradation by bee venom PLA(2)in vitro were obtained. In conclusion, direct conjugation between the drug and the phospholipid produces a complex having unique absorption properties that include: (1) a stable complex that does not undergo degradation in the GI tract; (2) permeation through the gut wall and entering intact to the enterocyte; and (3) association with chylomicron in the enterocyte and reaching the systemic circulation via the lymphatic route. These unique properties may be of interest in drug delivery.

Fetal weight estimation for prediction of fetal macrosomia: does additional clinical and demographic data using pattern recognition algorithm improve detection?

OBJECTIVE: The aim of this study was to test whether pattern recognition classifiers with multiple clinical and sonographic variables could improve ultrasound prediction of fetal macrosomia over prediction which relies on the commonly used formulas for the sonographic estimation of fetal weight. METHODS: THE SVM ALGORITHM WAS USED FOR BINARY CLASSIFICATION BETWEEN TWO CATEGORIES OF WEIGHT ESTIMATION: >4000gr and <4000gr. Clinical and sononographic input variables of 100 pregnancies suspected of having LGA fetuses were tested. RESULTS: Thirteen out of 38 features were selected as contributing variables that distinguish birth weights of below 4000gr and of 4000gr and above. Considering 4000gr. as a cutoff weight the pattern recognition algorithm predicted macrosomia with a sensitivity of 81%, specificity of 73%, positive predictive value of 81% and negative predictive value of 73%. The comparative figures according to the combined criteria based on two commonly used formulas generated from regression analysis were 88.1%, 34%, 65.8%, 66.7%. CONCLUSIONS: The SVM algorithm provides a comparable prediction of LGA fetuses as other commonly used formulas generated from regression analysis. The better specificity and better positive predictive value suggest potential value for this method and further accumulation of data may improve the reliability of this approach.

DP-155, a lecithin derivative of indomethacin, is a novel nonsteroidal antiinflammatory drug for analgesia and Alzheimer's disease therapy.

DP-155 is a lipid prodrug of indomethacin that comprises the latter conjugated to lecithin at position sn-2 via a 5-carbon length linker. It is cleaved by phospholipase A2 (PLA)(2) to a greater extent than similar compounds with linkers of 2, 3, and 4 carbons. Indomethacin is the principal metabolite of DP-155 in rat serum and, after DP-155 oral administration, the half-life of the metabolite was 22 and 93 h in serum and brain, respectively, compared to 10 and 24 h following indomethacin administration. The brain to serum ratio was 3.5 times higher for DP-155 than for indomethacin. In vitro studies demonstrated that DP-155 is a selective cyclooxygenase (COX)-2 inhibitor. After it is cleaved, its indomethacin derivative nonselectively inhibits both COX-1 and -2. DP-155 showed a better toxicity profile probably due to the sustained, low serum levels and reduced maximal concentration of its indomethacin metabolite. DP-155 did not produce gastric toxicity at the highest acute dose tested (0.28 mmol/kg), while indomethacin caused gastric ulcers at a dose 33-fold lower. Furthermore, after repeated oral dosing, gastrointestinal and renal toxicity was lower (10- and 5-fold, respectively) and delayed with DP-155 compared to indomethacin. In addition to reduced toxicity, DP-155 had similar ameliorative effects to indomethacin in antipyretic and analgesia models. Moreover, DP-155 and indomethacin were equally efficacious in reducing levels of amyloid ss (Ass)42 in transgenic Alzheimer's disease mouse (Tg2576) brains as well as reducing Ass42 intracellular uptake, neurodegeneration, and inflammation in an in vitro AD model. The relatively high brain levels of indomethacin after DP-155 administration explain the equal efficacy of DP-155 despite its low systemic blood concentrations. Compared to indomethacin, the favored safety profile and equal efficacy of DP-155 establish the compound as a potential candidate for chronic use to treat AD-related pathology and for analgesia.

Instability of Doppler cerebral blood flow in monochorionic twins.

OBJECTIVE: The purpose of this study was to evaluate Doppler flow velocity changes in cerebral vessels of monochorionic twins with twin-twin transfusion syndrome (TTTS). METHODS: Repeated Doppler umbilical and cerebral blood flow studies were performed in 7 twin pairs with TTTS. Eight monochorionic twin pairs and 11 dichorionic twin pairs served as control groups. The following Doppler parameters were assessed: umbilical artery pulsatility index (PI), middle cerebral artery (MCA) PI, cerebroplacental ratio, delta PI between the umbilical artery and MCA, and peak systolic velocity (PSV) in the MCA. RESULTS: Significant variations in PSV in the MCA and cerebral indices were found in the study group of monochorionic twins with TTTS. Periods of high PSV with low PI in the MCA were followed by lower PSV in the same fetus. Repeated measurements in the comparison groups were stable without significant variations. The delta cerebroplacental ratio was significantly higher in the study group (0.38 versus 0.09 and 0.19 in the comparison groups; P < .02). CONCLUSIONS: Significant changes in Doppler flow velocity and indices suggest instability of cerebral blood flow with episodes of "hyperperfusion" in monochorionic twins with TTTS. Further studies are needed to elucidate the relationship of these transient changes to neurologic sequelae in the neonate.

Subendometrial arterial spectral doppler assessment during IVF cycles and its correlation with treatment outcome.

The influence of blood flow impedance in subendometrial arteries on embryo implantation rate was investigated by transvaginal sonographic examination in in vitro fertilization (IVF) cycles. A total of 39 women undergoing IVF treatment were evaluated along the treatment cycle. Power and spectral Doppler studies of subendometrial arteries were performed to calculate the pulsatility index (PI), resistance index (RI) and systolic:diastolic ratio (S:D). The correlation between these parameters and pregnancy achievement was analyzed. Patients were grouped according to whether pregnancy was achieved or not. RI and S:D did not differ between the groups along the course of treatment. In pregnant patients, the PI was significantly lower in the beginning of the cycle than on the preovulation day and ovum pickup day. PI in the beginning of the treatment was significantly lower in pregnancy cycles than in nonpregnancy ones. A lower PI on day 1 was correlated with a better chance for pregnancy.

Decidualization of ovarian endometriosis during pregnancy mimicking malignancy.

OBJECTIVE: The purpose of this series is to present deciduosis (the formation of extrauterine decidua) as one of the differential diagnoses of a malignant tumor during pregnancy. METHODS: Two cases are described in which pregnant patients had a pelvic tumor. The lesions, which were diagnosed in the early second trimester, consisted of complex masses with an extensive blood supply and had a sonographic appearance of a malignant tumor. The high suspicion for malignancy necessitated surgical intervention. RESULTS: During surgery, the lesions were observed to be of an ovarian origin with papillary excrescences covering their exterior. The lesions were excised and sent for histologic examination. The results showed a markedly decidualized endometriotic cyst in both cases. CONCLUSIONS: This phenomenon is a diagnostic challenge and should be considered in the differential diagnosis of a malignant mass during pregnancy.

Diagnosis of pregnancy-associated uterine venous plexus thrombosis on the basis of transvaginal sonography.

OBJECTIVE: To describe the sonographic signs of uterine venous plexus thrombosis. METHODS: Four pregnant patients had a diagnosis of uterine venous plexus thrombosis in the first half of gestation. The diagnosis was based on transvaginal sonography only in 3 cases, and the fourth had magnetic resonance imaging corroboration. RESULTS: All 4 patients had similar sonographic features of uterine venous plexus thrombosis on transvaginal sonographic examination. The thrombi within the dilated veins were shown as elongated echogenic structures along the lumen that appeared round on transverse views of the affected veins. They showed swinging movements provoked by gentle transducer pressure. Power and color Doppler sonography enhanced the uterine venous plexus thrombosis diagnosis by showing blood flow around the thrombi. There were no signs of thromboembolic disease. Sonographic findings in deep leg veins and iliac veins were normal in all cases. Complete thrombophilia studies did not reveal any abnormalities. The uterine venous plexus thrombosis could not be detected on transabdominal sonography and was shown better by transvaginal sonography compared with magnetic resonance imaging. During 3 months of anticoagulation therapy, the thrombi gradually disappeared in all cases. CONCLUSIONS: Focusing on the pelvic veins while performing a transvaginal sonographic study during pregnancy may reveal important findings, which may have clinical implications. The therapeutic treatment of uterine venous plexus thrombosis is controversial and still empirical.