Prognostic value of diffusion-weighted magnetic resonance imaging of brain in fetal growth restriction: results of prospective multicenter study.

OBJECTIVE: To measure prospectively apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5th centile, and analyze their association with adverse perinatal outcome. METHODS: This was a prospective study involving six tertiary-level perinatal centers. In the period 22 November 2016 to 11 September 2017, we included singleton, small-for-gestational-age (SGA) fetuses with EFW ≤ 5th percentile, between 28 and 32 weeks of gestation, regardless of the umbilical artery Doppler and maternal uterine artery Doppler findings. A fetal magnetic resonance imaging (MRI) examination with diffusion-weighted sequences (DWI) was performed within 14 days following inclusion and before 32 weeks. ADC values were calculated in the frontal and occipital white matter, basal ganglia and cerebellar hemispheres. An ultrasound examination was performed within 1 week prior to the MRI examination. The primary outcome was a composite measure of adverse perinatal outcome, defined as any of the following: perinatal death; admission to neonatal intensive care unit with mechanical ventilation > 48 h; necrotizing enterocolitis; Grade III-IV intraventricular hemorrhage; periventricular leukomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with and those without adverse perinatal outcome was performed. The association between ADC values and adverse perinatal outcome was then analyzed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses. RESULTS: MRI was performed in 64 patients, of whom five were excluded owing to fetal movement artifacts on DWI and two were excluded for termination of pregnancy with no link to fetal growth restriction (FGR). One intrauterine death occurred secondary to severe FGR. Among the 56 liveborn neonates, delivered at a mean ± SD gestational age of 33.6 ± 3.0 weeks, with a mean birth weight of 1441 ± 566 g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotizing enterocolitis. Overall, therefore, seven out of 57 (12.3%) cases had an adverse perinatal outcome (95% CI, 3.8-20.8%). The ADC values in the frontal region were significantly lower in the group with adverse perinatal outcome vs those in the group with favorable outcome (mean values of both hemispheres, 1.68 vs 1.78 × 10-3 mm2 /s; P = 0.04). No significant difference in ADC values was observed between the two groups in any other cerebral territory. A cut-off value of 1.70 × 10-3 mm2 /s was associated with a sensitivity of 57% (95% CI, 18-90%), a specificity of 78% (95% CI, 63-88%), a positive predictive value of 27% (95% CI, 8-55%) and a negative predictive value of 93% (95% CI, 80-98%) for the prediction of adverse perinatal outcome. A mean frontal ADC value < 1.70 × 10-3 mm2 /s was not associated significantly with an increased risk of adverse perinatal outcome, either in the univariate analysis (P = 0.07), or when adjusting for gestational age at MRI and fetal sex (odds ratio (OR), 6.06 (95% CI, 0.9-37.1), P = 0.051) or for umbilical artery Doppler (OR, 6.08 (95% CI, 0.89-41.44)). CONCLUSION: This first prospective, multicenter, cohort study using DWI in the setting of SGA found lower ADC values in the frontal white-matter territory in fetuses with, compared with those without, adverse perinatal outcome. To determine the prognostic value of these changes, further standardized evaluation of the neurodevelopment of children born with growth restriction is required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Neonatal brain MRI: how reliable is the radiologist's eye?

INTRODUCTION: White matter (WM) analysis in neonatal brain magnetic resonance imaging (MRI) is challenging, as demonstrated by the issue of diffuse excessive high signal intensity (DEHSI). We evaluated the reliability of the radiologist's eye in this context. METHODS: Three experienced observers graded the WM signal intensity on axial T2-weighted 1.5T images from 60 different premature newborns on 2 occasions 4 weeks apart with a semi-quantitative classification under identical viewing conditions. RESULTS: The intra- and inter-observer correlation coefficients were fair to moderate (Fleiss' kappa between 0.21 and 0.60). CONCLUSION: This is a serious limitation of which we need to be aware, as it can lead to contradictory conclusions in the challenging context of term-equivalent age brain MRI in premature infants. These results highlight the need for a semiautomatic tool to help in objectively analyzing MRI signal intensity in the neonatal brain.

Periventricular hemorrhagic infarction (PVHI) associated with intraventricular hemorrhage (IVH) in premature infants: Outcome at 2 years of age.

OBJECTIVE: Neonates can develop periventricular hemorrhagic infarction (PVHI) in association with intraventricular hemorrhage (IVH). The prognosis of this condition remains under debate. The aim of this study was to compare the neurological outcome at 2 years of age for neonates who have IVH with and without PVHI. METHODS: This retrospective single-center study (2010-2017) included all neonates who had at least a grade II IVH on ultrasound (US). The population was divided into two groups: Group 1 had grade II-III IVH without PVHI and Group 2 had grade II-III IVH with PVHI. All clinical and imaging (US and magnetic resonance images) data were reviewed. Neurological sequelae were classified as either mild (favorable outcome), or moderate or severe (unfavorable outcome), based on the follow-up report at the age of 2 years. RESULTS: A total of 25 of the 46 infants meeting the inclusion criteria were excluded due to missing clinical or imaging data at diagnosis or follow-up. Of the remaining 21 infants, all were preterm and had grade II-III IVH, either with PVHI (n = 10) or without (n = 11). The neurological prognosis was unfavorable for both groups. Except for the size of the lesion, no radiological findings appeared to be significantly associated with an unfavorable prognosis. Overall, 11 of the infants died early in life; i.e., the mortality rate was 52% (n = 11/21). The deaths were not due to neurological complications of prematurity. C-section was more common in the PVHI group. CONCLUSION: PVHI does not appear to be predictive of an unfavorable outcome. Lesion size may be a predictive factor for an unfavorable prognosis in children with PVHI.

Feasibility of dynamic MRI for evaluating velopharyngeal insufficiency in children.

OBJECTIVE: To demonstrate the feasibility of dynamic MRI with near-real-time temporal resolution for analysing velopharyngeal closure. METHODS: Eleven children and young adults (seven girls, four boys, mean age: 8.4 years) with suspected velopharyngeal insufficiency (VPI), and one healthy volunteer underwent MRI (1.5 Tesla) using T2 fast imaging sequences. Imaging was done without any sedation at rest and during various phonations in the axial and sagittal planes. Images were analysed by two radiologists, a plastic surgeon and a speech therapist. RESULTS: The MRI examinations were well tolerated by even the youngest patient. A qualitative analysis found that the sagittal dynamic sequences during phonation were in relation to the clinical data in all patients. A quantitative analysis enabled calculation of the elevation angle of the soft palate in relation to the hard palate, the velar eminence angle and the percentage of reduction of the antero-posterior diameter of the pharyngeal lumen. CONCLUSION: Dynamic MRI is a non-invasive, rapid and repeatable method. It can be considered a complementary tool to endoscopy and fluoroscopy, particularly in children, for assessing VPI without any sedation or radiation exposure.

Fetal tumors of the choroid plexus: is differential diagnosis between papilloma and carcinoma possible?

Fetal choroid plexus tumors are uncommon. The prognosis is widely variable and depends on the histological findings: papilloma or carcinoma. We report a case of prenatal diagnosis of choroid plexus mass detected by ultrasound at 33 weeks of gestation. Prenatal (T1, T2, T2* and diffusion weighted sequences) magnetic resonance imaging (MRI) was used to rule out a hematoma. Follow-up examination by ultrasound and MRI revealed a significant increase in the volume of the mass, suggesting a diagnosis of malignant tumor. A healthy neonate was delivered by Cesarean section at 38 weeks of gestation. Full surgical excision of the tumor was performed at 20 days after delivery and histological analysis revealed a papilloma.

Pediatric outcome of children with the prenatal diagnosis of isolated septal agenesis.

BACKGROUND: Isolated Septal Agenesis (SA) is a rare disease with clinical outcomes (especially neurological outcomes) that are unknown. The purpose of this study was to evaluate the clinical outcome of these children. METHODS: We conducted a retrospective multicenter study of 17 children with an isolated SA or SA combined with a moderate ventricular dilatation (VD) that was diagnosed antenatally and confirmed by a magnetic resonance imaging (MRI) performed in the antenatal period. RESULTS: Of the 17 children, 14 had normal neurological examinations, 2 had language development delay and visuo-spatial dyspraxia, and 3 of the 17 children had behavioral problems. Eight children had neuropsychological evaluations, and the results were normal in six cases. There were 3 cases of septo-optic dysplasia (SOD) diagnosed postnatally, which highlighted the difficulties in assessing the optic tract and hypothalamic-pituitary region in antenatal imaging. Language delay and behavioral disorders were the main abnormalities at follow-up. CONCLUSION: The discovery of an isolated SA reveals the difficulties of prenatal diagnosis to correlate the neurological and functional prognosis to morphological findings. The prognosis seemed to be good. It appears necessary to improve the diagnostic performance of fetal brain imaging and to follow-up these children prospectively to assess their long-term cognitive-behavioral outcomes.

[Diffusion-weighted MR imaging of the normal fetal brain: marker of fetal brain maturation]. / Diffusion du cerveau foetal normal: limites et espoirs.

PURPOSE: To determine the reliability and variations of apparent diffusion coefficient (ADC) values in normal fetuses. Materials and methods. Retrospective study (2007-2008) on 22 normal fetal MR examinations, performed between 30 and 34 of gestation, using a routine protocol (T1W and T2W images in 3 planes, b=1,000 diffusion-weighted imaging) without sedation. ADC values were measured by placing 3 adjacent regions of interest (ROI) including a centrally located ROI over the right frontal and occipital white matter (6 ROI). STATISTICAL ANALYSIS: reproducibility of adjacent ADC values (intraclass correlation coefficient: ICC) and comparison between frontal and occipital ADC values (Wilcoxon). RESULTS: The mean ADC value was 1.78 mm(2)/s for the frontal white matter (+ or - 0.10) and 1.66 mm(2)/s for the occipital white matter (+ or - 0.12) with excellent reproducibility (ICC=0.91 in the frontal lobe) and good reproducibility for adjacent measurements (ICC=0.7). A linear inverse correlation existed between ADC values and gestational age in the occipital lobes, and a significant fronto-occipital gradient existed after 32 weeks of gestational age. CONCLUSION: ADC value measurements are reliable and inversely correlated with gestational age due to fetal brain maturation. The existence of a fronto-occipital gradient after 32 weeks of gestational age could be a marker of normal maturation used in clinical practice.

[Venous infarction of the neonate]. / L'infarctus veineux hémorragique du nouveau-né

PURPOSE: To determine the imaging features of hemorrhagic infarction in neonates. PATIENTS AND METHODS: Retrospective study (1998-2008) of 19 children (17 premature and 2 term deliveries) with early lobar hyperechogenicity on transfontanel US (TFUS). Group I: 11 born infants with clinical as well as TFUS and MRI follow-up. Group II: 8 premature infants deceased within a week from multisystem pathology, with neuropathological study available in 3 cases. RESULTS: Group I (n=11): periventricular hyperechogenicity in a frontal (7), frontoparietal (2), parietooccipital (1) and temporoparietal (1) distribution with developing cavitary change (n=6). MRI showed a cortex sparing intraparenchymal hematoma. Group II (n=8): periventricular hyperechogenicity in a frontal (4), frontoparietal or parietal (3) and occipital (1) with developing cavitary change (3). Neuropathological examination showed characteristic lesions of venous hemorrhagic infarction. Clinical outcome was generally favorable for the surviving infants with contralateral motor deficit (n=5) non-correlated to the extent of the initial lesions. CONCLUSION: Venous hemorrhagic infarction mainly affetcs premature infants and typically involves the periventricular frontal white matter. Prognosis is generally favorable. It is thus important to differentiate this entity from asymmetrical cystic periventricular leukomalacia with much different prognosis.

E.U. paediatric MOG consortium consensus: Part 4 - Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up.

E.U. paediatric MOG consortium consensus: Part 1 - Classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.

Cerebral biometry in fetal magnetic resonance imaging: new reference data.

OBJECTIVES: To provide normal magnetic resonance imaging (MRI) reference biometric data of the fetal brain, to evaluate reproducibility and gender effect, to compare the two cerebral hemispheres and to compare MRI with ultrasonographic biometry, in a large cohort. METHODS: Normal cerebral fetal MRI examinations were collected prospectively and several parameters were measured: the supratentorial space (bone and cerebral fronto-occipital and biparietal (BPD) diameters), the length of the corpus callosum (LCC), the surface area, height and anteroposterior diameter of the vermis, the transverse cerebellar diameter (TCD) and the anteroposterior diameter of the pons. We evaluated the interobserver reproducibility of measurements and the possible gender effect on measurements of bone BPD, TCD and LCC. We compared right and left hemispheres, right and left atria and ultrasound and MRI measurements. RESULTS: The study included 589 fetuses, ranging from 26 to 40 weeks. Normal values (from 3(rd) to 97(th) percentile) are provided for each parameter. Interobserver agreement was excellent, with an intraclass correlation coefficient (ICC) > 0.75 for many parameters. The gender effect was evaluated in 372 cases and did not reveal any clinically meaningful difference. Comparison between the right and left cerebral hemispheres and between the right and left atria did not reveal any meaningful differences. Ultrasound and MRI measurements of BPD and TCD were compared in 94 cases and 48 cases, respectively, and the agreement was excellent (ICC = 0.85). CONCLUSIONS: We present new reproducible reference charts for cerebral MRI biometry at 26-40 weeks' gestation, from a large cohort of fetuses.

[Fetal cerebral magnetic resonance imaging (MRI). Indications, normal and pathological patterns]. / Imagerie par résonance magnétique (IRM) foetale cérébrale : indications, aspects normaux et pathologiques.

Fetal MRI is a specific imaging modality, always performed after a reference ultrasound examination. The decision to perform an MRI-scan must take into account the anxiety constantly generated by the need for this unusual examination during pregnancy. To date, no side-effect associated with 1.5 tesla magnets has been described. Compared to ultrasonography, fetal brain MRI provides better contrast between grey and white matter, as well as better delineation of the brainstem (pontic curvature) and the cerebellum (lobules and fissures). However, it often remains difficult to inform parents about prognosis. Thereby, it is of utmost importance to be familiar with the definite criteria associated with a poor neurological prognosis such as lack of pontic curvature or as diffuse or bilateral cortical malformations. This has to be considered within the framework of French regulations which allow pregnancy termination with no time limit. The optimal timing to perform a fetal MRI-scan depends on the context. The period between 27 and 30 weeks of gestation is a good balance between gestational age and gyration or sulcation development. The main ultrasonographic findings requiring MRI are ventriculomegalies and posterior fossa abnormalities. MRI exploration can sometimes be performed despite a normal ultrasonography in case of genetic disorders such as tuberous sclerosis and lissencephalies. In addition to its diagnostic value towards decision to terminate pregnancy, fetal MRI can be used as "in vivo autopsy", in case of expected technical difficulties or refusal of post-abortion examinations by relatives. Technical advances (real time and specific sequences like diffusion tensor and spectroscopy) and prospective clinical studies will probably improve the efficiency of this method to assess neurological prognosis.

Imaging features of atypical bleeds in young patients with hemophilia.

Hemarthroses and muscle bleeds are well-known and well-documented complications in pediatric and young adult hemophilia patients. In contrast, deep bleeds in atypical locations can be a diagnostic challenge, since clinicians and radiologists are often unfamiliar with their clinical and radiological features. Some atypical bleeds, however, can be life-threatening or severely disabling, highlighting the need for prompt, accurate diagnosis. Rare bleeds include central nervous system bleeds (including intracranial and spinal hematomas), urogenital bleeds, intra-abdominal bleeds (mesenteric and gastrointestinal wall hematomas) and pseudo tumors in unusual locations like the sinonasal cavities. Because clinical assessment can be difficult, clinicians and radiologists should be aware of the possibility of these rare complications in their hemophilia patients, so that they can avoid unnecessary invasive diagnostic and surgical procedures and institute prompt, appropriate treatment. The purpose of this review is to illustrate the imaging features of bleeds that occur in rare locations in young (i.e., children and young adults) patients with hemophilia to make the reader more familiar with these conditions.

Craniosynostosis and metabolic bone disorder. A review.

INTRODUCTION: Some metabolic bone disorders may result in the premature closure of one or more calvarial sutures during childhood, potentially leading to a cranioencephalic disproportion. The aim of this paper is to review the characteristics and consequences of craniosynostosis associated with metabolic disorder. MATERIAL AND METHODS: A review of the literature on metabolic forms of craniosynostosis was performed. RESULTS: The most common forms of craniosynostosis associated with metabolic bone disorder were isolated sagittal suture fusion with or without scaphocephaly, and sagittal suture fusion associated with coronal suture fusion (oxycephaly) or also with lambdoid suture fusion (pansynostosis). Synostosis may be well-tolerated, but in some subjects results in neurodevelopmental and functional impairment that is sometimes severe. CONCLUSION: The impact of metabolic synostosis is very variable, depending on the specific underlying metabolic disease, with a large spectrum of morphological and functional consequences. Diagnosis should be early and management should be carried out by a multidisciplinary team with expertise in both rare skeletal disorders and craniosynostosis. The impact of emergent medical therapies recently developed for some of these diseases will be assessed by systematic coherent follow-up of international registries.

[Fetal MR: evaluation of patient's experiences and practical implications]. / Imagerie par Résonance Magnétique foetale : évaluation du vécu des patientes et implications pratiques.

PURPOSE: Several studies have evaluated the experience of patients undergoing obstetrical US. No similar study evaluated the impact of fetal MR on patients. Our hypothesis was that the fetal MR is more anxiety-producing than fetal US. The goal was to acquire insight to improve the experience for patients. PATIENTS AND METHODS: Prospective dual-center study of 100 patients who answered a questionnaire validated by radiologists, obstetricians and psychologists. In one of the two centers, po sedation was routinely used in all patients. The questionnaires were qualitatively and quantitatively analyzed. RESULTS: Results confirm the more stressful nature of MR compared to US (72%). One third of patients (34%) would have liked information about the procedure, diagnostic limitations, and mainly the impact on the fetus, especially with regards to noise. Most patients reported discomfort (duration, position) (82%) and stated that it would be preferable to be accompanied (83%). The perception of fetal movements by the mother was related to stress, noise and vibration of the MR examination. CONCLUSION: MR increases the anxiety related to prenatal diagnosis by its setting and sometimes the lack of information, namely the fetal risk. It is important to maintain a dialogue between obstetricians and mothers from the indication to the acquisition of the MR. The diagnostic limitations of MR for prenatal diagnosis should be clearly stated. A discussion between the radiologist and mother after completion of the examination is desirable, if only to discuss the patient's or couple's comments.

[Cerebral infarction in full-term newborns: MR imaging features]. / Accident vasculaire cérébral (AVC) du nouveau-né à terme: aspects en IRM.

PURPOSE: Perinatal stroke is the most frequent cause of congenital hemiplegia. The MR imaging features of cerebral infarction in full-term newborns will be reviewed and the underlying etiologies discussed. PATIENTS AND METHODS: Retrospective study (1999-2005) including 15 newborn infants without history of fetal distress with early seizures (before day 7) with ischemic or hemorrhagic infarct on MR. All MR examinations were reviewed by consensus (MBD, CHA) using a checklist and results were correlated with findings at clinical follow-up (mean follow-up of 1 year). RESULTS: MR showed ischemic strokes in 10 infants (5 left, 4 right, 1 bilateral) in the middle (n=9) or anterior (n=1) cerebral artery distribution or with extensive bilateral distribution. The cortex and subcortical regions were involved in all cases with ipsilateral basal ganglia/internal capsule extension in 4 cases. The imaging features were related to the timing of the MR examination: within 5 days (n=4): cortical effacement on T1W and T2W images, increased signal on DWI with reduced signal on ADC; between 7-14 days (n=6): T1W hyperintense and T2W hypointense cortex. Five infants had unifocal (3/5) or multifocal (2/5) hemorrhagic infacrtion. Of 13 patients followed-up from 3 months to 3 years (1 lost to follow-up, 1 deceased), 11 had no clinical deficits, 1 had hemiparesis, and 1 had asymmetrical muscle tone. The latter 2 infants had involvement of the posterior limb internal capsule, with basal ganglia and hemispheric involvement. In the literature, this association of lesions is considered predictive of hemiplegia and a high rate of sequelae is reported following neonatal stroke: 50-75% with motor deficit and/or seizure disorder. The 4 infacts with hemorrhagic infarction followed-up for 14 months to 5 years had a globally favorable neurological outcome. CONCLUSION: Cerebral infacrtion in full-term newborns without associated risk factor is variable and should be recognized. Early MR, before day 2, with diffusion-weighted sequences, allows diagnosis but follow-up MR after day 7 is necessary to better depict the extent of permanent lesions. The presence of hemorrhage is not a predictive factor of poor neurological outcome.