A new automatic algorithm to extract craniofacial measurements from fetal three-dimensional volumes.

OBJECTIVES: Three-dimensional (3D) ultrasound is useful in the prenatal evaluation of fetal craniofacial structures, particularly as it provides a multiplanar view. However, an expert must designate the area of interest and the appropriate view, making measurement of fetal structures using 3D ultrasound both time-consuming and subjective. In this study we propose an image analysis system that measures automatically and precisely the fetal craniofacial structures and evaluate its performance in the second trimester of pregnancy using a new 3D volume analysis algorithm. METHODS: A universal facial surface template model containing the geometric shape information of a fetal craniofacial structure was constructed from a fetal phantom. Using the proposed image analysis system we fitted this stored template model using a model deformation approach to individual fetal 3D facial volumes from 11 mid-trimester fetuses, and extracted automatically the following standard measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital diameter (BOD) and distance between vertex and nasion (VN). The same five parameters were measured manually by an expert and the results compared. RESULTS: Comparison of the algorithm-based automatic measurements with manual measurements made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD, 0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences between automatic and manual measurements. CONCLUSION: Our proposed system measures precisely the fetal craniofacial structures using 3D ultrasound, making it potentially useful for clinical service. This system could also be applied to other clinical fields in future testing.

Molecular analysis of HLA-DRB1 allelic associations with systemic lupus erythematous and lupus nephritis in Taiwan.

To evaluate the association of human leukocyte antigen (HLA)-DRB1 alleles with systemic lupus erythematosus (SLE) and lupus nephritis (LN) in the Taiwanese population, and to investigate the possible association of HLA-DRB1 alleles with disease severity in LN. HLA-DRB1 alleles were studied in 105 SLE patients (82 patients with LN, 23 patients without LN) and 855 healthy controls by polymerase chain reaction and sequence-based typing assays. The frequency of the HLA class II alleles DRB1*0301 (Odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.31-3.10, Pc = 0.02) and DRB1*1501 (OR = 2.06, 95% CI = 1.36-3.13, Pc = 0.01) were both increased in SLE patients, compared to healthy controls. The frequency of DRB1*1202 was significantly lower in LN patients than in SLE patients without nephritis (OR = 0.23, 95% CI = 0.09-0.57, Pc = 0.01). No specific allele was significantly associated with an increased or decreased risk for severity of LN in this sample. In Taiwanese people, the DRB1*0301 and DRB1*1501 alleles are significant risk factors for SLE, while the DRB1*1202 allele is protective for LN.

Standardization of three-dimensional images in obstetrics and gynecology: consensus statement.

Standardization of the display of ultrasound images has so far only been achieved in transabdominal two-dimensional (2D) sonography. In contrast, there is a lack of uniformity in the demonstration of transvaginal 2D ultrasound images. The described non-uniformity frequently leads to confusion in the assessment of an image, in particular with regard to the accurate anatomical assignment of left/right and dorsal/ventral. Three-dimensional (3D) sonography offers a unique opportunity to avoid this confusion in the interpretation of ultrasound images, because, independent of primary volume acquisition, the volume can always be rotated so that the stored object can at all times be visualized in a known anatomical position, rendering it of no importance whether the image acquired transvaginally is demonstrated from above or from below. This will also be important in allowing fusion of ultrasound image data with computed tomographic, magnetic resonance and/or positron emission tomography images. In this article we suggest that standardization of transabdominal and transvaginal 3D images does not only provide the inexperienced physician/sonographer with a guide to spatial orientation, but also serves to avoid erroneous topographical interpretations.

Infusion of human umbilical cord blood cells protect against cerebral ischemia and damage during heatstroke in the rat.

Intravenously delivered human umbilical cord blood cells (HUCBC) have been previously shown to improve both morphologic and functional recovery of heat-stroked rats. To extend these findings, we examined both the morphologic and functional alterations in the presence of HUCBC or human peripheral mononuclear cells (PBMC) 24 h before initiation of heatstroke. Anesthetized rats, 1 day before the initiation of heatstroke, were divided into three major groups and given the following: (a) serum-free lymphocyte medium (0.3 ml) intravenously; (b) PBMC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium); or (c) HUCBC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium). Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. In vehicle-treated heatstroke rats, their mean arterial pressure, cerebral blood flow, and brain PO(2) were all lower than in normothermic controls after the onset of heatstroke. However, their body temperatures and striatal levels of inducible nitric oxide synthase (iNOS)-dependent NO, ischemia and damage markers (e.g., glycerol, glutamate, and lactate/pyruvate ratio), and neuronal damage in the striatum were all greater. The heatstroke-induced arterial hypotension, cerebral ischemia and hypoxia, and increased levels of iNOS-dependent NO in the striatum were all significantly reduced by pretreatment with HUCBC, but not with PBMC. Moreover, HUCBC were localized by immunohistochemistry and PCR analysis in the injured brain structures and spleen. These findings indicate that HUCBC transplantation, in addition to having therapeutic values, can be a good choice for preventing heatstroke occurrence.

Three-dimensional power Doppler imaging of early-stage cervical cancer.

OBJECTIVES: To characterize intratumoral vascularization in early-stage cervical cancer by three-dimensional (3D) power Doppler ultrasound. METHODS: One hundred and forty-one patients with carcinoma of the uterine cervix and 30 normal controls were studied by transvaginal 3D power Doppler ultrasound. The tumor volume of the cervical cancer was determined. The blood flow within the tumor or normal cervix was measured and expressed as the vascularization index (VI), flow index (FI) and vascularization flow index (VFI). RESULTS: Of the 141 patients with cervical cancer, 44 patients had undergone prior cervical conization. Eighty-seven patients had measurable cervical tumors, of whom five had had prior conization. Abundant intratumoral power Doppler signals could be detected, and the VI, FI and VFI were significantly elevated in cervical cancer patients compared with women with a normal cervix and patients in whom no cervical tumor could be detected (P < 0.05, one-way ANOVA). We observed four types of intratumoral vascularity patterns, which did not significantly differ in VI, FI and VFI: localized, peripheral, scattered and single-vessel types. Cervical tumor volume was positively correlated with FI (linear regression, r = 0.373, P = 0.001), but not with VI or VFI. CONCLUSIONS: 3D power Doppler ultrasound provides a useful tool to investigate intratumoral vascularization and volume of cervical cancer.

Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women.

Depression and anxiety disorders often coexist clinically and both are known to have a genetic basis, but the mode of inheritance is too complicated to be determined so far. Serotonin is the biogenic amine neurotransmitter most commonly associated with depression and anxiety. Since tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, its role in the pathophysiology of these psychiatric diseases has been intensively studied. In this study, we examined whether polymorphism of the TPH1 gene is related to the etiology of major depression, anxiety and comorbid depression and anxiety. Five single nucleoside polymorphisms of the TPH1 gene were studied in a population-based sample of postpartum Taiwanese women consisting of 120 subjects with depression or/and anxiety and 86 matched normal controls. A significant difference (P = 0.0107) in genotype frequency for the T27224C polymorphism was found between the comorbid and normal groups, and risk analysis showed that the C allele conferred a strong protective effect (odds ratio = 0.27; 95% confident interval = 0.11-0.7). Three-allele haplotypes involving T27224C polymorphism were constructed and haplotype associations between particular haplotype combinations and various diseases identified. However, the associations were weak and the overall haplotype frequency profiles in all groups were similar. The results suggest that depression, anxiety, and comorbid depression and anxiety disorders may have related etiologies. In addition, this study suggests that the TPH1 gene might play a role in the pathogenesis of these closely related disorders.

Three-dimensional power Doppler imaging of ovarian stromal blood flow in women with endometriosis undergoing in vitro fertilization.

OBJECTIVE: The aims of this retrospective study were to investigate whether the quantification of ovarian stromal blood flow and/or leptin concentration are predictive of in vitro fertilization (IVF) outcomes in women after laparoscopic ovarian cystectomy for large endometriomas. METHODS: Twenty-two women undergoing IVF after laparoscopic surgery for ovarian endometriomas (> 6 cm) comprised the study group. Twenty-six women with tubal factor infertility constituted the control group. Ovarian stromal blood flow was evaluated by three-dimensional (3D) power Doppler ultrasound imaging using virtual organ computer-aided analysis (VOCAL( trade mark )). Serum and follicular fluid (FF) leptin concentrations were quantified using an enzyme-linked immunosorbent assay kit. RESULTS: There were significantly decreased ovarian stromal blood flow parameters (including vascularization index, flow index (FI), and vascularization flow index) in the endometriosis group without an evident difference in total ovarian volume on the day of human chorionic gonadotropin. The value of FF leptin demonstrated a negative correlation with ovarian stromal FI in the control group, but there was a loss of this effect in the endometriosis group. CONCLUSIONS: Quantification of ovarian stromal blood flow by 3D power Doppler ultrasound in women with endometriosis may provide an important prognostic indicator in those undergoing IVF.

Prenatal diagnosis of cleft palate by three-dimensional ultrasound.

Prenatal diagnosis of cleft palate is very important to prenatal consultation and management after birth. To examine if three-dimensional (3-D) ultrasound (US) is an accurate diagnostic method for clinical use, we analyzed our experience in detecting cleft palate by 3-D US. From June 1996 to January 2000, 21 fetuses with facial clefts were scanned by 2-D US, as well as by 3-D US. The coronal and oblique planes were reconstructed by 3-D US to detect the cleft palate. In addition, level II US was performed to find any possibly associated anomalies. All the scans were recorded on optic disks for final analysis. In our study, the gestational age when prenatal diagnosis was made by US initially was between 20 and 34 weeks. The accuracy for prenatal diagnosis of cleft lip with or without cleft palate by 3-D US was 100%, which was superior to that by 2-D US (p < 0.05). In addition, we proposed a novel method to evaluate the cleft palate systemically by 3-D US. In conclusion, from our study, fetuses with cleft lip combined with or without cleft palate can be easily differentiated by 3-D US. The reconstruction of coronal and oblique planes by 3-D US is a powerful tool for detecting cleft palate.

Prenatal diagnosis of twin-twin transfusion syndrome complicated with hydrops fetalis at 14 weeks of gestation.

Twin-twin transfusion syndrome (TTTS) may complicate multiple pregnancy. Monochorionic discordant twins with oligohydramnios and polyhydramnios may be diagnostic. Hydrops fetalis is particularly ominous. All the signs can appear independently at any stage of gestation. However, TTTS with hydrops fetalis in early pregnancy is rare. We report here a case of TTTS complicated with hydrops fetalis diagnosed at 14 weeks of gestation. Our case may be one of the earliest cases of the prenatal diagnosis of TTTS complicated with hydrops fetalis in the literature.

Successful pregnancy by transmyometrial and transtubal embryo transfer after IVF in a patient with congenital cervical atresia who underwent uterovaginal canalization during Caesarean section: case report.

Successful pregnancy in a patient with congenital cervical atresia is a great challenge for assisted reproductive techniques and reproductive medicine. We report a case of successful pregnancy by transmyometrial and transtubal embryo transfer simultaneously after in-vitro fertilization (IVF) in a 33 year-old patient with congenital cervical atresia diagnosed at the age of 18 years. The patient had experienced cyclic abdominal pain and amenorrhoea since she was 13 years old. She had had two unsuccessful attempts to create a new uterovaginal canal in another hospital. At the age of 32 years, she was referred to our unit and had a successful pregnancy after transmyometrial and transtubal embryo transfer. Caesarean section was performed at 36 weeks gestation due to progressive pre-eclampsia and gestational diabetes. A healthy male baby weighing 2812 g was safely delivered. Uterovaginal canalization with amniotic membrane for the covering of the neo-endocervical wall was performed during Caesarean section. Normal menstrual outflow and symptomatic relief have continued for 5 months after the operation. To the best of our knowledge, this is the first reported case of successful pregnancy by transmyometrial and transtubal embryo transfer as well as uterovaginal canalization performed during Caesarean section in a patient with congenital cervical atresia.

Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy.

OBJECTIVE: The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women. METHODS: Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale. RESULTS: Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse. CONCLUSIONS: The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT.

Assessment of fetal cerebellar volume using three-dimensional ultrasound.

The purposes of this study were to assess the fetal cerebellar volume during normal gestation using three-dimensional (3-D) ultrasound (US) and to establish a normal chart of fetal cerebellar volume using Altman's model of statistics. In total, 231 healthy fetuses were studied for assessment of cerebellar volume using a 3-D US volume scanner. The fetuses to be studied were selected to give a cross-sectional series (i.e., each fetus was examined only once). Polynomial regression analysis was calculated to find the best-fit model using gestational age as the independent variable and cerebellar volume as the dependent variable. Altman's model was used to calculate the age-related reference centiles for the variance of cerebellar volume. In addition, common fetal growth indices, such as biparietal diameter, occipitofrontal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight, were also measured for the correlation between cerebellar volume and these indices. Our results indicated that the fetal cerebellar volume was highly correlated with gestational age in normal pregnancies with the best-fit polynomial regression equation of a second-order (r = 0.91, p < 0.0001). In addition, fetal cerebellar volume in normal gestation is also highly correlated with common fetal growth indices, such as biparietal diameter, occipitofrontal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight (all p < 0.0001). Following the Altman's model, a normal growth chart of fetal cerebellar volume was established for clinical reference. In conclusion, with 3-D US, the assessment of fetal cerebellar volume becomes feasible. We believe that fetal cerebellar volume assessed by 3-D US may be useful in detecting cerebellar hypoplasia and relevant syndromes prenatally.

Fetal ear assessment and prenatal detection of aneuploidy by the quantitative three-dimensional ultrasonography.

The purposes of this study were to use quantitative three-dimensional (3-D) ultrasonography to establish the normal charts of three fetal ear-growth indexes, (ear length, ear width and ear area), and to validate their efficacy in the prenatal diagnosis of fetal trisomies, either separately or as a combination. Using quantitative 3-D ultrasonography, we performed a prospective study to measure the three fetal ear growth indexes (i.e., ear length, ear width and ear area) in 129 singleton pregnancies, including 122 normal fetuses and 7 trisomies. The ear shape was also evaluated in these fetuses using both 2-D and 3-D ultrasonography. Our results showed that: First, 3-D ultrasonography offers better visualization and easier evaluation of fetal ears than 2-D ultrasonography. Second, when using the quantitative assessment of 3-D ultrasonography, the measurements of ear length, ear width and ear area were all correlated significantly with gestational age in normal pregnancies (r = 0.881, 0.848, and 0.890, respectively). In addition, 3 of 7 fetal trisomies had ear length below the tenth percentile, 1 had ear width below the tenth percentile, and 2 had ear area below the tenth percentile. Furthermore, with the combination of these three measurements, (including ear length, ear width and ear area), the sensitivity in detecting fetal trisomies was elevated to 57.1% and the specificity was 83.2%. In conclusion, 3-D ultrasonography reduces the limitations of 2-D ultrasonography in the evaluation of fetal ears. However, fetal ear measurement may not be used as a single ultrasonographic parameter in identifying aneuploid fetuses. We recommend using the combination of these three ear growth indexes to enhance the detection rate of aneuploidy.

Systemic assessment of fetal hemodynamics by Doppler ultrasound.

The aim of our study was to investigate the parameters of fetal circulation of normal pregnancies and their relationship to fetal cardiac output. We performed a cross-sectional study of 315 normal singleton pregnancies between 20 and 40 weeks' gestation without fetal chromosomal or structural malformations. After follow-up to delivery, 212 patients who fit all the criteria were enrolled for final analysis. Blood flow velocity waveforms were obtained from the tricuspid and mitral ventricular inflow, ascending aorta (AAO), pulmonary artery (PA), middle cerebral artery (MCA), renal artery (RA), umbilical artery (UA), descending aorta (DAO), inferior vena cava (IVC) and ductus venosus (DV) using duplex (real-time Doppler) ultrasound (US) scanner. The peak velocity of DV, AAO, PA and MCA were also obtained. At the intracardiac level, the ratio of peak flow velocity of E wave to peak flow velocity of A wave (E:A ratio) of mitral valve (MV) increased more rapidly than tricuspid valve (TV) E:A ratio. For the great vessels, aortic peak velocity remained higher than the pulmonary peak velocity with advancing gestation. The cardiac output closely correlated to the cardiac compliance and flow resistance indices at arterial and venous level. The acceleration time in the fetal arteries increased with advancing gestation in AAO, PA, MCA and DAO, but it decreased in RA and kept constant in UA. In addition, the acceleration time of UA was unrelated to cardiac output. The changes of the fetal intracardiac, arterial and venous impedances were remarkable through the gestation and related to cardiac output. Fetal cardiac output correlated well with the changes of arterial resistance, except with the DAO. The ventricular compliance increased with advancing gestation, especially in the left side, and was highly related to the change of cardiac output. The acceleration time in major arteries positively correlated with the gestational age and cardiac output, except in UA and RA; this indicates the difference of the changes of mean arterial pressure in uteroplacental circulation, fetal organs and great vessels. In conclusion, the fetal cardiac output correlated well with the ventricular compliance and was influenced by both hemodynamic changes in peripheral resistance and mean arterial pressure.

Prenatal diagnosis of alobar holoprosencephaly by two-dimensional and three-dimensional ultrasound.

The aim of this study is to evaluate the sonographic characteristics of alobar holoprosencephaly (AH) in utero. Seventeen cases were diagnosed at 16-30 weeks' gestation by two-dimensional and three-dimensional ultrasound from October 1994 to December 1998. In this series, the prenatal prevalence was 1 out of 415 and the detection rate of AH by prenatal ultrasound was 100%. Eleven cases (64.7%) had concurrent facial anomalies. Cleft lip and hypotelorism were the most common associated facial anomalies (72.7%). Two cases (11.8%) were twin pregnancy with one fetus affected. We present one of the largest series in the literature and compare it with previous reports. From this series, we concluded that: (1) intracranial findings, including monoventricle, fused thalami, and the absence of midline structures, were reliable sonographic characteristics for prenatal diagnosis; (2) cleft lip and hypotelorism seemed to be more common associated facial malformations than cyclopia or cebocephaly with AH; and (3) although three-dimensional ultrasound did not change the diagnosis of AH made by two-dimensional ultrasound in this series, three-dimensional ultrasound does assist in defining the severity and extent of AH.

Evolution of exon 1 of the dopamine D4 receptor (DRD4) gene in primates.

The dopamine D4 receptor (DRD4) gene exhibits a large amount of expressed polymorphism in humans. To understand the evolutionary history of the first exon of DRD4-which in humans contains a polymorphic 12bp tandem duplication, a polymorphic 13bp deletion, and other rare variants-we examined the homologous exon in thirteen other primate species. The great apes possess a variable number of tandem repeats in the same region as humans, both within and among species. In this sense, the 12bp tandem repeat of exon 1 is similar to the 48bp VNTR of exon 3 of DRD4, previously shown to be polymorphic in all primate species examined. The Old World monkeys show no variation in length, and a much higher conservation of amino acid sequence than great apes and humans. The New World monkeys show interspecific differences in length in the region of the 12bp polymorphism, but otherwise show the higher conservation seen in Old World monkeys. The different patterns of variation in monkeys compared to apes suggest strong purifying selective pressure on the exon in these monkeys, and somewhat different selection, possibly relaxed selection, in the apes.