Brain metabolism in fetal intrauterine growth restriction: a proton magnetic resonance spectroscopy study.

OBJECTIVE: The purpose of this study was to investigate alterations in brain metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution of blood flow. STUDY DESIGN: Biometry and Doppler assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and cerebral redistribution and in 41 appropriately grown control subjects. Proton magnetic resonance spectroscopy of the fetal brain was then performed to determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr. RESULTS: Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and creatine peaks were identified in all these spectra; lactate was present in 5 IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were significantly lower in IUGR fetuses with cerebral redistribution. CONCLUSION: Cerebral redistribution is associated with altered brain metabolism that is evidenced by a reduction in NAA:Cho and NAA:Cr ratios.

Early adverse perinatal complications in preterm growth-restricted fetuses.

INTRODUCTION: Growth-restricted fetuses are at increased risk of adverse perinatal outcome when compared to their normally grown counterparts. The additional risks associated with growth restriction in preterm fetuses are not well quantified, and this meta-analysis serves to address this uncertainty. MATERIALS AND METHODS: This is a meta-analysis and meta-regression of all relevant studies published since 1997 investigating perinatal outcome in preterm growth-restricted fetuses. RESULTS: Growth-restricted fetuses across all gestational ages were found to be at significant risk of having low Apgar scores at 5 min, sepsis, intracranial haemorrhage, intrauterine and neonatal death, necrotising enterocolitis and respiratory complications. Although this risk reduced as gestation increased, it remained amplified in growth-restricted fetuses when compared to normally grown fetuses. CONCLUSION: This large meta-analysis for the first time quantifies the additional perinatal risks associated with preterm fetal growth restriction and may help counsel parents about the complications these fetuses face following birth.

Severe hypertension in pregnancy.

Severe hypertension in pregnancy is defined as a sustained systolic blood pressure of 160 mmHg or over or diastolic blood pressure of 110 mmHg or over and should be assessed in hospital. Severe hypertension before 20 weeks' gestation is rare and usually due to chronic hypertension; assessment for target organ damage and exclusion of secondary hypertension are warranted. The most common cause of severe hypertension in pregnancy is pre-eclampsia, which presents after 20 weeks' gestation. This warrants more rapid control of blood pressure due to the risk of haemorrhagic stroke, and intravenous antihypertensive agents may be required. Treatment is determined by licensing, availability and clinician experience, with no high-level evidence to guide prescribing. Labetalol is the agent most commonly used, both orally and intravenously, in pregnancy in the UK. Severe hypertension is a risk factor for sustained hypertension after pregnancy. Hypertension in pregnancy is associated with increased cardiovascular risk.

Neuromodulative treatment with percutaneous tibial nerve stimulation for intractable detrusor instability: outcomes following a shortened 6-week protocol.

OBJECTIVE: To describe our initial outcome data following a shortened 6-week treatment protocol with percutaneous tibial nerve stimulation (PTNS) in women with overactive bladder syndrome (OABS) unresponsive to bladder retraining and anticholinergic therapy. PATIENTS AND METHODS: This was a prospective observational study over a 6-month period. In all, 43 women with OABS refractory to medical therapy were treated with a shortened PTNS protocol that consisted of 6 weekly 30 min sessions. Bladder symptom diaries and health-related quality of life (HRQL) assessed using the short-form seven-item self-report. Incontinence Impact Questionnaire (IIQ-7) were completed before and after treatment. A positive response was defined as: (i) OAB symptoms no longer being bothersome; (ii) reduction by half in frequency episodes and (iii) reduction by 25% in IIQ-7 outcomes. RESULTS: All 43 women (median age 55.3 years) completed six treatments with a positive response rate of 69.7%. In the positive responders, the median daytime and nocturnal frequency was reduced by half after 6 weeks of treatment (11.8 vs 6.9 and 3.5 vs 1.8, respectively, P < 0.05) and the patients reported fewer urge leak episodes per 24 h (median 3.5 vs 2.4, P < 0.05). The median IIQ-7 scores improved by 25% (30.4 vs 24.3, P < 0.05) in responders, while the median number of pads changed in 24 h also decreased by 34% (3.8 vs 2.5, P < 0.05). The median acceptability of the technique when scored by Visual Analogue Score was 9.6/10 and no side-effects were reported. CONCLUSION: A shortened 6-week treatment with PTNS appears to be successful, with a significant reduction in symptoms and improvement in HRQL. This early data suggest that the duration of treatment for peripheral neuromodulation can be halved compared with the conventional 12 weeks, which would make it more acceptable and cost effective for patients. A randomised controlled trial of 6 weeks vs 12 weeks of PTNS therapy would be useful in determining the optimal duration of treatment.

PVR: Patch-to-Volume Reconstruction for Large Area Motion Correction of Fetal MRI.

In this paper, we present a novel method for the correction of motion artifacts that are present in fetal magnetic resonance imaging (MRI) scans of the whole uterus. Contrary to current slice-to-volume registration (SVR) methods, requiring an inflexible anatomical enclosure of a single investigated organ, the proposed patch-to-volume reconstruction (PVR) approach is able to reconstruct a large field of view of non-rigidly deforming structures. It relaxes rigid motion assumptions by introducing a specific amount of redundant information that is exploited with parallelized patchwise optimization, super-resolution, and automatic outlier rejection. We further describe and provide an efficient parallel implementation of PVR allowing its execution within reasonable time on commercially available graphics processing units, enabling its use in the clinical practice. We evaluate PVR's computational overhead compared with standard methods and observe improved reconstruction accuracy in the presence of affine motion artifacts compared with conventional SVR in synthetic experiments. Furthermore, we have evaluated our method qualitatively and quantitatively on real fetal MRI data subject to maternal breathing and sudden fetal movements. We evaluate peak-signal-to-noise ratio, structural similarity index, and cross correlation with respect to the originally acquired data and provide a method for visual inspection of reconstruction uncertainty. We further evaluate the distance error for selected anatomical landmarks in the fetal head, as well as calculating the mean and maximum displacements resulting from automatic non-rigid registration to a motion-free ground truth image. These experiments demonstrate a successful application of PVR motion compensation to the whole fetal body, uterus, and placenta.

DeepCut: Object Segmentation From Bounding Box Annotations Using Convolutional Neural Networks.

In this paper, we propose DeepCut, a method to obtain pixelwise object segmentations given an image dataset labelled weak annotations, in our case bounding boxes. It extends the approach of the well-known GrabCut [1] method to include machine learning by training a neural network classifier from bounding box annotations. We formulate the problem as an energy minimisation problem over a densely-connected conditional random field and iteratively update the training targets to obtain pixelwise object segmentations. Additionally, we propose variants of the DeepCut method and compare those to a naïve approach to CNN training under weak supervision. We test its applicability to solve brain and lung segmentation problems on a challenging fetal magnetic resonance dataset and obtain encouraging results in terms of accuracy.

Placenta Maps: In Utero Placental Health Assessment of the Human Fetus.

The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.

Normative biometry of the fetal brain using magnetic resonance imaging.

The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21-38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery.

Myo-inositol metabolism in appropriately grown and growth-restricted fetuses: a proton magnetic resonance spectroscopy study.

OBJECTIVE: Myo-inositol (Myo-ins) is a marker of neuroglial cells, being present in the astrocytes of brain tissue, but also functions as an osmolyte. Numbers of astrocytes are known to increase following injury to the brain. Growth-restricted fetuses are at increased risk of later neurodevelopmental impairments even in the absence of overt lesions and despite preserved/increased cerebral blood flow. This study aims to investigate brain Myo-ins metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution using magnetic resonance spectroscopy (MRS) at a short echo time. STUDY DESIGN: Biometry and Doppler assessment of blood flow was assessed using ultrasound in 28 fetuses with IUGR and 47 appropriately grown control subjects. MRI was used to exclude overt brain injury. Proton magnetic resonance spectroscopy of the fetal brain was then performed at an echo time of 42 ms to examine the Myo-ins:Choline (Cho), Myo-ins:Creatine (Cr) and Cho:Cr ratios. RESULTS: No alterations in brain Myo-ins:Cho, Myo-ins:Cr or Cho:Cr ratios were detected between appropriately grown and growth restricted fetuses. CONCLUSIONS: IUGR is not associated with a measureable difference in brain myo-inositol ratios. This may be due to the protective effects of preserved cerebral blood flow in growth restriction and comparable astrocyte numbers when compared to controls.

Foetal volumetry using magnetic resonance imaging in intrauterine growth restriction.

OBJECTIVES: We used magnetic resonance imaging (MRI) to perform volumetry of foetuses with and without growth restriction, and identify deviations in organ growth. STUDY DESIGN: 20 growth restricted and 19 normal foetuses were scanned once during pregnancy at gestational age 20.53-36.57 weeks. MRI scans were performed on a 1.5T system using ssFSE sequences. Manual segmentation of whole body, brain, heart, lung, liver, thymus and kidney volume was performed. Data on the severity of foetal growth restriction and pregnancy outcome was collected. RESULTS: There was a significant reduction in foetal whole body volume and volume of all internal organs except the brain in growth restricted foetuses. A brain:liver ratio above 3.0 was associated with a 3.3 fold increase in risk of perinatal mortality (95% CI=1.68-6.47). CONCLUSION: MRI provides an accurate assessment of foetal organ growth. It may have a role to play in monitoring disease severity and the effect of future interventions.

Proton magnetic resonance spectroscopy in the fetus.

Magnetic Resonance Imaging (MRI) has become an established technique in fetal medicine, providing complementary information to ultrasound in studies of the brain. MRI can provide detailed structural information irrespective of the position of the fetal head or maternal habitus. Proton Magnetic Resonance Spectroscopy ((1)HMRS) is based on the same physical principles as MRI but data are collected as a spectrum, allowing the biochemical and metabolic status of in vivo tissue to be studied in a non-invasive manner. (1)HMRS has been used to assess metabolic function in the neonatal brain but fetal studies have been limited, primarily due to fetal motion. This review will assess the technique and findings from fetal studies to date.

The pressure profile test is more sensitive and specific than Palmer's test in predicting correct placement of the Veress needle.

OBJECTIVES: Although the majority of laparoscopic complications result from improper Veress needle placement, the safety tests commonly used to determine correct placement are not always reliable. A prospective observational study (Canadian Task Force Classification II-2) was set up to determine the reliability of Palmer's and pressure profile tests in predicting the correct intraperitoneal placement of the Veress needle prior to insufflation. STUDY DESIGN: One hundred consecutive women undergoing gynaecological laparoscopic surgery between September 2006 and June 2007 were recruited. The operating surgeons conducted Palmer's and pressure profile tests in all 100 cases and recorded the ease with which these tests were performed and whether or not they felt that the needle placement was correct. They were also asked to comment on the saline drop test and double click acoustic test if appropriate. RESULTS: The overall sensitivity of Palmer's test was 0.92 while its specificity was 0.5. The overall sensitivity and specificity of the pressure profile test were 0.99 and 0.75, respectively, making this a more reliable test for predicting intraperitoneal placement of the Veress needle. CONCLUSIONS: The pressure profile test was a more reliable guide to confirming the correct placement of the Veress needle as a negative test is more likely to indicate failure to achieve intraperitoneal placement.