Latest developments in post-mortem foetal imaging

A sustained decline in parental consent rates for perinatal autopsies has driven the development of less-invasive methods for death investigation. A wide variety of imaging modalities have been developed for this purpose and include post-mortem whole body magnetic resonance imaging (MRI), ultrasound, computed tomography (CT) and micro-focus CT techniques. These are also vital for “minimally invasive” methods, which include potential for tissue sampling, such as image guidance for targeted biopsies and laparoscopic-assisted techniques. In this article, we address the range of imaging techniques currently in clinical practice and those under development. Significant advances in high-field MRI and micro-focus CT imaging show particular promise for smaller and earlier gestation foetuses. We also review how MRI biomarkers such as diffusion-weighted imaging and organ volumetric analysis may aid diagnosis and image interpretation in the absence of autopsy data. Three-dimensional printing and augmented reality may help make imaging findings more accessible to parents, colleagues and trainees.     

The use of fetal MRI for renal and urogenital tract anomalies

Fetal anomalies are detected in approximately 2% of all fetuses and, among these, genitourinary tract abnormalities account for 30% to 50% of all structural anomalies present at birth. Although ultrasound remains the first line diagnostic modality, fetal MRI provides important additional structural and functional information, especially with the development of faster sequences and the use of functional sequences. The added value of MRI-based imaging is three-fold: (a) improvement of diagnostic accuracy by adequate morphological examination, (b) detection of additional anomalies, and (c) in addition, MRI has the potential to provide information regarding renal function. In this review, we describe the role of fetal MRI in the anatomical evaluation of renal and urogenital tract anomalies, and we also touch upon the contribution of functional MRI to the diagnostic workup of these conditions.     

Magnetic resonance spectroscopy of the fetal brain

Fetal magnetic resonance spectroscopy (MRS) is technically feasible in utero and demonstrates similar findings to those observed in neonatal populations. MRS can provide additional information to conventional T1- and T2-weighted imaging of the fetal brain. It is of particular use when subtle changes are present on conventional fetal MRI sequences, and when imaging fetuses at risk of brain injury and metabolic abnormalities. Copyright © 2009 John Wiley & Sons, Ltd.     

Minimally invasive fetal postmortem examination using magnetic resonance imaging and computerised tomography: current evidence and practical issues

For a variety of reasons, acceptance of traditional postmortem examination following foetal or neonatal death has declined significantly in recent years in the UK. Here, we review the case for the development of less invasive autopsy using combined investigations including imaging techniques, in particular, magnetic resonance imaging and computerised tomography. Copyright © 2010 John Wiley & Sons, Ltd.     

Fetal ear measurements in the prenatal detection of trisomy 21

Although prominent fetal nuchal folds, short long bones, echogenic bowel, and renal pelviectasis have been shown to be associated with trisomy 21, none has acceptable diagnostic efficacy. Diminished fetal ear lengths measured by ultrasound have recently been reported as yet another potential morphological marker for the prenatal detection of trisomy 21. To investigate this further, we measured ear lengths and widths of normal (n = 107) and trisomy 21 (n = 25) second-trimester formalin-preserved fetuses. The normal ear growth characteristics are described and compared with those of trisomy 21 fetuses. The normal fetal ear shape, not unlike that of the neonates, manifested a marked variation. When the ear lengths and widths were regressed against gestational age, the slopes of the regression lines for the two groups were found to be different (P < 0·001). However, despite the statistically significant difference between the ear sizes of normal and trisomy 21 fetuses, the wide range of normal variation seen at each gestational age means that the fetal ear measurements are not diagnostically helpful.     

Prenatal diagnosis of cystic fibrosis: Ultrasonographic appearance of meconium ileus in the fetus

Four often fetuses carrying a risk of 1:4 for cystic fibrosis were found to have low levels of microvillar enzymes in the amniotic fluid obtained between 17 and 18 weeks' gestational age. On sonography performed prior to the amniocentesis, three fetuses showed enlarged bowel loops. At autopsy, meconium ileus was detected. Enlarged bowel loops are a sign which has not been described previously so early in pregnancies.     

The MRI spectrum of congenital cytomegalovirus infection

Human cytomegalovirus (CMV) is an ubiquitous pathogen, with a high worldwide seroprevalence. When acquired in the prenatal period, congenital CMV (cCMV) is a major cause of neurodevelopmental sequelae and hearing loss. cCMV remains an underdiagnosed condition, with no systematic screening implemented in pregnancy or in the postnatal period. Therefore, imaging takes a prominent role in prenatal diagnosis of cCMV. With the prospect of new viable therapies, accurate and timely diagnosis becomes paramount, as well as identification of fetuses at risk for neurodevelopmental sequelae. Fetal magnetic resonance imaging (MRI) provides a complementary method to ultrasound (US) in fetal brain and body imaging. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to US in their detection. Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. However, when seen in combination these should raise the suspicion of fetal infection, highlighting the need for a full fetal assessment. Still, some fetuses deemed normal on prenatal imaging are symptomatic at birth or develop delayed cCMV-associated symptoms, leaving room for improvement of diagnostic tools. Advanced MR sequences may help in this field and in determining prognosis, but further studies are needed.     

Brain cortical assessment by MRI in fetuses with left congenital diaphragmatic hernia

Objective

To evaluate fetal brain development using MRI (magnetic resonance imaging) in CDH (congenital diaphragmatic hernia).

Methods

52 isolated left CDH and 104 control fetuses were imaged using MRI. Brain morphometry (Biparietal diameter—BPD, brain fronto-occipital diameter—BFOD, third ventricle, posterior ventricles, transcerebellar diameter—TCD, anteroposterior and craniocaudal cerebellar vermis diameter—AP and CC) and cortical structures (bilateral cingulate fissure—CF, insular fissure—IF, insular depth - ID) were compared with controls using Mann–Whitney test.

Results

Median gestational age at MRI (p = 0.95)and the median biparietal diameter (p = 0.737) were comparable. Among morphometric parameters, only the brain fronto-occipital diameter was significantly smaller in CDH (p = 0.001) and the third ventricle was significantly greater in CDH (<0.0001). Among cortical structures, the cingulate and insular fissures were significantly deeper in CDH fetuses (p < 0.0001) as the insular depth ID was smaller in CDH (p < 0.03).

Conclusions

CDH fetuses have a smaller fronto-occipital diameter, reduced insular depth, deeper cingulate and insular fissure, and greater third ventricle width as compared to controls. These findings suggest that left CDH may have an impact on fetal brain development with an overall reduction in brain volume.     

Genetic syndromes associated with isolated fetal growth restriction

Early onset fetal growth restriction (FGR) may be due to impaired placentation, environmental or toxic exposure, congenital infections or genetic abnormalities. Remarkable research, mainly based on retrospective series, has been published on the diverse genetic causes. Those have become more and more relevant with the improvement in the accuracy of the analysis techniques and the rising of breakthrough genomewide methods such as the whole genome sequencing. However, no publication has presented an integrated view of management of those fetuses with an early and severe affection. In this review, we explored to which extent genetic syndromes can cause FGR fetuses without structural defects. The most common chromosomal abnormalities (Triploidies and Trisomy 18), submicroscopic chromosomal anomalies (22q11.2 microduplication syndrome) and single gene disorders (often associated with mild ultrasound findings) related to early and severe FGR had been analysed. Finally, we addressed the impact of epigenetic marks on fetal growth, a matter of growing importance. At the end of this review, we should be able to provide an adequate counseling to parents in terms of diagnosis, prognosis and management of those pregnancies.     

Bilateral renal agenesis in three consecutive siblings

We report here an unusual recurrence of bilateral renal agenesis (BRA) in three consecutive siblings. Chromosome analysis was normal, as were renal ultrasound studies on both parents and their surviving child. Ultrasound was employed prenatally to diagnose Potter's syndrome in both of the recurrences, and autopsy confirmed BRA in otherwise normal fetuses. Recurrence of BRA points to the usefulness of ultrasound in monitoring subsequent pregnancies in couples who have had one such occurrence. Ultrasound studies should also be performed in non-affected family members to detect the presence of asymptomatic anomalies of the genitourinary system, but a negative family study does not preclude recurrence of BRA.     

Early prenatal detection of diastrophic dysplasia

Diastrophic dysplasia, an autosomal recessive disorder, results in severe short-limbed dwarfism, progressive spinal and joint problems, and secondary psychosocial disability. The results of treatments are unsatisfactory. Four pregnant mothers at risk for an affected fetus were studied with an ultrasound scanner at 16 and 19 weeks of gestation. Each mother had a previous child with diastrophic dysplasia. The biparietal distance and the length of the long bones of the extremities were normal in three fetuses, whereas in one fetus there was a 30 per cent shortening of all long bones. The biparietal distance corresponded with the gestational age in all fetuses. In one fetus, diastrophic dysplasia was confirmed by fetoscopy and fetal radiograph at 19 weeks of gestation after the parents had decided to terminate the pregnancy. The skeletal radiograph and autopsy findings of the fetus verified the diagnosis. All other mothers were followed with repeated ultrasound examinations, and they delivered healthy babies. The retrospective follow-up of the four previous pregnancies and of the present one with affected fetuses disclosed that two mothers had had vaginal bleeding, two lymphedema, one abdominal pains, and one mother had had polyhydramnios. These complications were, however, mild and transient, and they could not be regarded as specific for pregnancies with affected fetuses.     

MR imaging of the fetal musculoskeletal system

Magnetic resonance imaging (MRI) appears to be increasingly used, in addition to standard ultrasonography for the diagnosis of abnormalities in utero. Previous studies have recently drawn attention to the technical refinement of MRI to visualize the fetal bones and muscles. Beyond commonly used T2-weighted MRI, echoplanar, thick-slab T2-weighted and dynamic sequences, and three-dimensional MRI techniques, are about to provide new imaging insights into the normal and the pathological musculoskeletal system of the fetus. This review emphasizes the potential significance of MRI in the visualization of the fetal musculoskeletal system. © 2012 John Wiley & Sons, Ltd.     

First-trimester diagnosis of osteogenesis imperfecta associated with encephalocele by conventional and three-dimensional ultrasound

To illustrate the three-dimensional sonographic features of a rare genetic disorder, we report on prenatal diagnosis of osteogenesis imperfecta congenita associated with encephalocele at 13 weeks of gestation, using conventional and three-dimensional ultrasound. Because the parents were first-degree cousins and on the basis of the family history, a recessive autosomal inheritance was suspected. Of seven previous pregnancies, five were unaffected and two had been terminated in the second trimester owing to a similar abnormality (one affected boy and one affected girl). In the case we present, the diagnosis was made on the basis of two-dimensional ultrasound performed by physicians aware of the history; the quality of three-dimensional ultrasound imaging suggests that this technique might have contributed toward establishing a precise diagnosis in the absence of a positive family history. Besides, the global view provided by three-dimensional surface-rendering images made the parents more confident of the accuracy of the diagnosis. Although osteogenesis imperfecta congenita is generally considered as autosomal dominant, the case we report suggests that it may be inherited in a recessive autosomal fashion at least when associated with encephalocele. Three-dimensional ultrasound confirmed the conventional two-dimensional examination and was helpful in convincing the parents of the accuracy of the diagnosis. Copyright © 2003 John Wiley & Sons, Ltd.     

Usefulness of automated chromatography for rapid fetal blood analysis for second trimester prenatal diagnosis of β-thalassemia

Prenatal diagnosis of β-thalassemia is now ideally done in the first trimester of pregnancy by chorionic villus tissue DNA analysis. Nevertheless, fetal blood analysis in the second trimester is required either when the mutation in both parents cannot be characterised or when the couple comes late for investigations. We evaluated the usefulness of analysis of fetal blood on the Biorad Variant Hemoglobin Testing System using the β-thalassemia short programme in comparison with the conventional globin biosynthesis in 58 pregnancies. The β/α biosynthesis ratios in 13 homozygous fetuses ranged from 0 to 0.03 and the adult hemoglobin (HbA) levels by automated chromatography varied from 0% to 0.4%. The normal or heterozygous fetuses had β/α ratios of >0.04 and HbA levels ranging from 2.1% to 10.6%. In 17 fetuses we also correlated the β gene mutations with the predicted genotypes using automated high-performance liquid chromatography (HPLC). Follow-up of 18 unaffected fetuses using the Variant System at birth showed a significant increase in HbA levels. Copyright © 2002 John Wiley & Sons, Ltd.     

Intrauterine brain teratoma: a case report of imaging (US,MRI) with neuropathologic correlations

Fetal brain tumors are rare and teratoma is considered as the most common. Fetal MR Imaging is currently used to evaluate cases of ventricular dilatation. We report a case of cerebral immature teratoma detected by ultrasonography because of ventricular dilatation at 24 gestational weeks. MRI was the more accurate imaging method in depicting the tumor and its consequences on brain development as well as in taking a decision with regard to the management of pregnancy. Copyright © 2003 John Wiley & Sons, Ltd.     

Challenges in non-invasive prenatal screening for sub-chromosomal copy number variations using cell-free DNA

Non-invasive prenatal screening (NIPS) has revolutionized the approach to prenatal fetal aneuploidy screening. Many commercial providers now offer analyses for sub-chromosomal copy number variations (CNVs). Here, we review the use of NIPS in the context of screening for microdeletions and microduplications, issues surrounding the choice of disorders tested for, and the advantages and disadvantages associated with the inclusion of microdeletions to current NIPS. Several studies have claimed benefits; however, we suggest that microdeletions have not demonstrated a low enough false positive rate to be deemed practical or ethically acceptable, especially considering their low positive predictive values. Because a positive NIPS result should be confirmed using diagnostic techniques, and false positive rates are as high as 90% for some microdeletions, diagnostic testing seems preferable when the goal is to maximize the detection of microdeletion or microduplication syndromes.     

The diagnostic potential of fetal renal biopsy

The feasibility of fetal renal biopsy has been investigated in order to assess the diagnostic value of the histological specimen. Two fetuses with a severe bilateral renal abnormality (multicystic dysplastic kidney, Meckel-Gruber syndrome with polycystic kidney) and one fetus with Down syndrome (no detectable structural anomaly) were sampled. Histological findings in the biopsy specimens of cases 1 and 2 were diagnostic of an early obstructive renal disease. In case 3 , the findings were consistent with normal development for gestational age of the kidney. Fetal renal biopsy is technically feasible; histological examination of the samples showed a good correlation with postnatal findings. Further studies of its diagnostic value are required.     

海上注聚井渗氮油管腐蚀失效原因

渤海S油田A2井渗氮防腐油管在注聚过程中发现多处腐蚀穿孔,为避免换管柱后再次发生腐蚀失效,通过腐蚀形貌观察、腐蚀产物分析、腐蚀介质分析对A2井油管腐蚀失效原因进行了研究。认为A2井油管部分渗氮层脱落,形成了电化学腐蚀的阳极,这是造成局部腐蚀的根本原因。注入水中存在较高含量的氯离子和硫酸盐还原菌,加剧了腐蚀进程,造成油管腐蚀穿孔,形成了以FeCO_3为主的腐蚀产物。建议加强渗氮油管质量管控,防止入井前渗氮层脱落,同时在注入水中加入杀菌剂减少细菌对腐蚀的影响,并在井下安装牺牲阳极短节预防腐蚀。     

Agenesis of the corpus callosum: What to tell expecting parents?

Agenesis of the corpus callosum (ACC) is one of the most common brain malformations, with an incidence estimated to range from 0.5 to 70 in 10,000 among the general population. Prenatal diagnosis is made via ultrasound; however, fetal MRI is useful to confirm or exclude the presence of associated cerebral abnormalities–mostly cortical malformations–that may affect postnatal prognosis. When no additional central nervous system (CNS) or extra CNS anomalies are identified and no genetic cause is found, an isolated ACC is diagnosed. Overall, in cases of ACC, an underlying genetic cause can be identified in up to 12.5% with chromosomal microarray (CMA) and up to 47% with whole exome sequencing (WES). In cases where ACC is the only anomaly detected, the yield of WES is 30%. Postnatal outcomes are variable and depend on whether the condition is isolated or not. In truly isolated ACC, outcomes range from normal in 65% of cases through mild to severe neurodevelopmental impairments in 35% of cases. An interdisciplinary team of medical experts is key in guiding parents toward informed decision-making in pregnancies complicated by ACC. Considering current and expected advancements in genetic testing and imaging technologies in upcoming years, we herein summarize current recommendations for the management and prenatal counseling of expecting parents of fetuses with ACC. Our review pertains primarily to expecting parents of fetuses with complete ACC.     

Fetal brain imaging in isolated congenital heart defects – a systematic review and meta-analysis

Congenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical search was performed, and 34 studies evaluating the fetal brain [magnetic resonance imaging (MRI) or ultrasound] in isolated CHD were included (1990–2015). Data regarding cerebral abnormalities, head circumference growth and middle cerebral artery flow were extracted. Prenatal MRI was studied in ten articles (445 fetuses), resulting in a pooled prevalence of 18% (95%CI −6%; 42%) for combined structural and acquired cerebral abnormalities. Prenatal head circumference was studied in 13 articles (753 fetuses), resulting in a pooled z-score of −0.51 (95%CI −0.84; −0.18). Doppler was studied in 21 articles (1412 fetuses), resulting in a lower middle cerebral artery pulsatility index (z-score −0.70 95%CI −0.99; −0.41) in left-sided CHD only. We conclude that prenatal MRI and ultrasound demonstrate brain abnormalities, delay in head growth and brainsparing in subgroups of CHD. However, large MRI studies are scarce, and ultrasound data are biased towards severe and left-sided CHD. Long-term follow-up studies correlating prenatal findings with postnatal ND outcome are limited, and data are lacking to support counseling families regarding ND outcome based on prenatal findings suggestive of altered brain development. © 2016 John Wiley & Sons, Ltd.