Background Late-onset intrauterine growth restriction (IUGR) results from a failure of the placenta to supply adequate nutrients and oxygen to the rapidly growing late-gestation fetus. Limitations in ...current monitoring methods present the need for additional techniques for more accurate diagnosis of IUGR in utero. New magnetic resonance imaging (MRI) technology now provides a noninvasive technique for fetal hemodynamic assessment, which could provide additional information over conventional Doppler methods. Objective The objective of the study was to use new MRI techniques to measure hemodynamic parameters and brain growth in late-onset IUGR fetuses. Study Design This was a prospective observational case control study to compare the flow and T2 of blood in the major fetal vessels and brain imaging findings using MRI. Indexed fetal oxygen delivery and consumption were calculated. Middle cerebral artery and umbilical artery pulsatility indexes and cerebroplacental ratio were acquired using ultrasound. A score of ≥ 2 of the 4 following parameters defined IUGR: (1) birthweight the third centile or less or 20% or greater drop in the centile in estimated fetal weight; (2) lowest cerebroplacental ratio after 30 weeks less than the fifth centile; (3) ponderal index < 2.2; and (4) placental histology meets predefined criteria for placental underperfusion. Measurements were compared between the 2 groups (Student t test) and correlations between parameters were analyzed (Pearson’s correlation). MRI measurements were compared with Doppler parameters for identifying IUGR defined by postnatal criteria (birthweight, placental histology, ponderal index) using receiver-operating characteristic curves. Results We studied 14 IUGR and 26 non-IUGR fetuses at 35 weeks’ gestation. IUGR fetuses had lower umbilical vein ( P = .004) and pulmonary blood flow ( P = .01) and higher superior vena caval flow ( P < .0001) by MRI. IUGR fetuses had asymmetric growth but smaller brains than normal fetuses ( P < .0001). Newborns with IUGR also had smaller brains with otherwise essentially normal findings on MRI. Vessel T2s, oxygen delivery, oxygen consumption, middle cerebral artery pulsatility index, and cerebroplacental ratio were all significantly lower in IUGR fetuses, whereas there was no significant difference in umbilical artery pulsatility index. IUGR score correlated positively with superior vena caval flow and inversely with oxygen delivery, oxygen consumption, umbilical vein T2, and cerebroplacental ratio. Receiver-operating characteristic curves revealed equivalent performance of MRI and Doppler techniques in identifying IUGR that was defined based on postnatal parameters with superior vena caval flow area under the curve of 0.94 (95% confidence interval, 0.87–1.00) vs a cerebroplacental ratio area under the curve of 0.80 (95% confidence interval, 0.64–0.97). Conclusion MRI revealed the expected circulatory redistribution in response to hypoxia in IUGR fetuses. The reduced oxygen delivery in IUGR fetuses indicated impaired placental oxygen transport, whereas reduced oxygen consumption presumably reflected metabolic adaptation to diminished substrate delivery, resulting in slower fetal growth. Despite brain sparing, placental insufficiency limits fetal brain growth. Superior vena caval flow and umbilical vein T2 by MRI may be useful new markers of late-onset IUGR.
Summary Background Multiple sclerosis (MS) diagnostic criteria incorporate MRI features that can be used to predict later diagnosis of MS in adults with acute CNS demyelination. To identify MRI ...predictors of a subsequent MS diagnosis in a paediatric population, we created a standardised scoring method and applied it to MRI scans from a national prospective incidence cohort of children with CNS demyelination. Methods Clinical and MRI examinations were done at the onset of acute CNS demyelination and every 3 months in the first year after that, and at the time of a second demyelinating attack. MS was diagnosed on the basis of clinical or MRI evidence of relapsing disease. Baseline MRI scans were assessed for the presence of 14 binary response parameters. Parameters were assessed with a multiple tetrachoric correlation matrix. Univariate analyses and multivariable Cox proportional hazards models were used to identify predictors of MS. Findings Between Sept 1, 2004, and June 30, 2010, 332 children and adolescents were assessed for eligibility. 1139 scans were available from 284 eligible participants who had been followed up for 3·9 (SD 1·7) years. 57 (20%) were diagnosed with MS after a median of 188 (IQR 144–337) days. Seven of 14 binary response parameters were retained. The presence of either one or more T1-weighted hypointense lesions (hazard ratio 20·6, 95% CI 5·46–78·0) or one or more periventricular lesions (3·34, 1·27–8·83) was associated with an increased likelihood of MS diagnosis (sensitivity 84%, specificity 93%, positive predictive value 76%, negative predictive value 96%). Risk for MS diagnosis was highest when both parameters were present (34·27, 16·69–70·38). Although the presence of contrast enhancement, cerebral white matter, intracallosal, and brainstem lesions was associated with MS in the univariate analyses, these parameters were not retained in the multivariable models. Interpretation Specific MRI parameters can be used to predict diagnosis of MS in children with incident demyelination of the CNS. The ability to promptly identify children with MS will enhance timely access to care and will be important for future clinical trials in paediatric MS. Funding Canadian Multiple Sclerosis Scientific Research Foundation.
A mouse model of antepartum stillbirth Rahman, Anum, Ms; Cahill, Lindsay S., PhD; Zhou, Yu-Qing, PhD ...
American journal of obstetrics and gynecology,
10/2017, Volume:
217, Issue:
4
Journal Article
Peer reviewed
Abstract Background Many stillbirths of normally-formed fetuses in the third trimester could be prevented via delivery if reliable means to anticipate this outcome existed. However, since the ...etiology of these stillbirths is often unexplained and, although the underlying mechanism is presumed to be hypoxia from “placental insufficiency”, the placentas often appear normal on histopathologic examination. Gestational age is a risk factor for antepartum stillbirth, with a rapid rise in stillbirth rates after 40 weeks gestation. We speculate that a common mechanism may explain antepartum stillbirth in both the late-term and post-term periods. Mice also show increasing rates of stillbirth when pregnancy is artificially prolonged. The model therefore affords an opportunity to characterize events that precede stillbirth. Objective To prolong gestation in mice and monitor fetal and placental growth and cardiovascular changes. Study Design From E15.5 to E18.5, pregnant CD-1 mice received daily progesterone injections to prolong pregnancy by an additional 24-hour period (to embryonic day 19.5). To characterize fetal and placental development, experimental assays were performed throughout late gestation (E15.5 to E19.5), including post-natal day 1 pups as controls. In addition to collecting fetal and placental weights, we monitored fetal blood flow using Doppler ultrasound and examined the feto-placental arterial vascular geometry using microcomputed tomography. Evidence of hypoxic organ injury in the fetus was assessed using magnetic resonance imaging and pimonidazole immunohistochemistry. Results At E19.5, mean fetal weights were reduced by 14% compared with control post-natal day 1 pups. Ultrasound biomicroscopy showed that fetal heart rate and umbilical artery flow continued to increase at E19.5. Despite this, the E19.5 fetuses had significant pimonidazole staining in both brain and liver tissue, indicating fetal hypoxia. Placental weights at E19.5 were 21% lower than at term (E18.5). Microcomputed tomography showed no change in quantitative morphology of the feto-placental arterial vasculature between E18.5 and E19.5. Conclusions Prolongation of pregnancy renders the murine fetus vulnerable to significant growth restriction and hypoxia due to differential loss of placental mass rather than any compromise in feto-placental blood flow. Our data are consistent with a hypoxic mechanism of antepartum fetal death in human term and post-term pregnancy and validates the inability of umbilical artery Doppler to safely monitor such fetuses. New tests of placental function are needed to identify the late-term fetus at risk of hypoxia in order to intervene by delivery to avoid antepartum stillbirth.
This review summarizes results from studies that have applied advanced magnetic resonance (MR) imaging techniques to patients with pediatric-onset multiple sclerosis (MS), and includes a discussion ...of cortical imaging techniques, volumetry, magnetization transfer and diffusion tensor imaging, proton magnetic resonance spectroscopy, and functional MR imaging. Multicenter studies on the sensitivity of these techniques to natural history of disease and treatment response are required before their implementation into clinical practice.