CT venography for the diagnosis of postpartum venous thromboembolism: a prospective multi-center cohort study.

OBJECTIVES: To assess the role of CT venography (CTV) in the diagnosis of venous thromboembolism (VTE) during the postpartum period. MATERIALS AND METHODS: This multicenter prospective cohort study was conducted between April 2016 and April 2020 in 14 university hospitals. All women referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE) within the first 6 weeks postpartum were eligible. All CTPAs were performed on multidetector CT machines with the usual parameters and followed by CTV of the abdomen, pelvis, and proximal lower limbs. On-site reports were compared to expert consensus reading, and the added value of CTV was assessed for both. RESULTS: The final study population consisted of 123 women. On-site CTPA reports mentioned PE in seven women (7/123, 5.7%), all confirmed following expert consensus reading, three involving proximal pulmonary arteries and four limited to distal arteries. Positive CTV was reported on-site in nine women, five of whom had negative and two indeterminate CTPAs, bringing the VTE detection rate to 11.4% (14/123) (95%CI: 6.4-18.4, p = 0.03). Expert consensus reading confirmed all positive on-site CTV results, but detected a periuterine vein thrombosis in an additional woman who had a negative CTPA, increasing the VTE detection rate to 12.2% (15/123) (95%CI: 7.0-19.3, p = 0.008). Follow-up at 3 months revealed no adverse events in this woman, who was left untreated. Median Dose-Length-Product was 117 mGy.cm for CTPA and 675 mGy.cm for CTPA + CTV. CONCLUSION: Performing CTV in women suspected of postpartum PE doubles the detection of venous thromboembolism, at the cost of increased radiation exposure. CLINICAL RELEVANCE STATEMENT: CTV can help in the decision-making process concerning curative anticoagulation in women with suspected postpartum PE, particularly those whose CTPA results are indeterminate or whose PE is limited to the subsegmental level. KEY POINTS: Postpartum women are at risk of pulmonary embolism, and CT pulmonary angiography can give equivocal results. CT venography (CTV) positivity increased the venous thromboembolism detection rate from 5.7 to 11.4%. CTV may help clinical decision-making, especially in women with indeterminate CTPA results or subsegmental emboli.

Recurrent de novo mutations in CLDN5 induce an anion-selective blood-brain barrier and alternating hemiplegia.

Claudin-5 is the most enriched tight junction protein at the blood-brain barrier. Perturbations in its levels of expression have been observed across numerous neurological and neuropsychiatric conditions; however, pathogenic variants in the coding sequence of the gene have never been reported previously. Here, we report the identification of a novel de novo mutation (c.178G>A) in the CLDN5 gene in two unrelated cases of alternating hemiplegia with microcephaly. This mutation (G60R) lies within the first extracellular loop of claudin-5 and based on protein modelling and sequence alignment, we predicted it would modify claudin-5 to become an anion-selective junctional component as opposed to a purely barrier-forming protein. Generation of stably transfected cell lines expressing wild-type or G60R claudin-5 showed that the tight junctions could still form in the presence of the G60R mutation but that the barrier against small molecules was clearly attenuated and displayed higher Cl- ion permeability and lower Na+ permeability. While this study strongly suggests that CLDN5 associated alternating hemiplegia is a channelopathy, it is also the first study to identify the conversion of the blood-brain barrier to an anion-selective channel mediated by a dominant acting variant in CLDN5.

Renal vein thrombosis in neonates: a case series of diagnosis, treatment and childhood kidney function follow-up.

BACKGROUND: Neonatal renal vein thrombosis (NRVT) is a rare condition with little data available. METHODS: We retrospectively analyzed newborns diagnosed with NRVT admitted to 3 pediatric nephrology units in Paris from 2005 to 2020. RESULTS: Twenty-seven patients were analyzed (male = 59%). The median age at diagnosis was 2.5 days (1 - 4.5). Diagnosis was suspected based on at least one of the three cardinal signs of renal vein thrombosis in 93%: flank mass (67%), hematuria (67%) and thrombocytopenia (70%). In all patients, diagnosis was confirmed by ultrasound. All patients had at least one known perinatal risk factor. A prothrombotic risk factor was found in 13 patients (48%). NRVT was unilateral in 70%, involving the left renal vein in 58%. Among 25 treated patients, 19 (76%) received low molecular weight heparin (LMWH) as initial therapy, 2 (8%) received unfractionated heparin and 4 (16%) received fibrinolysis. Median duration of treatment was 8 weeks (4 - 12). Bleeding occurred significantly more often with fibrinolysis than with LMWH/supportive therapy (3 of 4: 75% vs 0 of 4: 0%, p = 0.05). Clot resolution in patients treated with fibrinolysis did not differ significantly from those treated with LMWH/supportive therapy. After a median follow-up of 5.7 years (3 years - 9.9 years), pathological kidney features were observed in 73% of the patients (19 of 26), kidney atrophy in 18 (69%), hypertension in 2 (8%), chronic kidney disease (CKD) in 1 (4%) and proteinuria in 2 (8%). CONCLUSIONS: NRVT remains a challenging condition, which still requires further study because of its associated morbidity. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evolution of Extracranial Internal Carotid Artery Disease in Children With Sickle Cell Anemia.

BACKGROUND: Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. METHODS: Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. RESULTS: Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1-9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT (P=0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and -0.18 (0.55) with CTT (P=0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. CONCLUSIONS: Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.

Cerebral injuries in neonatal encephalopathy treated with hypothermia: French LyTONEPAL cohort.

BACKGROUND: Hypothermia is widely used for infants with hypoxic-ischemic neonatal encephalopathy but its impact remains poorly described at a population level. We aimed to describe brain imaging in infants born at ≥36 weeks' gestation, with moderate/severe encephalopathy treated with hypothermia. METHODS: Descriptive analysis of brain MRI and discharge neurological examination for infants included in the French national multicentric prospective observational cohort LyTONEPAL. RESULTS: Among 575 eligible infants, 479 (83.3%) with MRI before 12 days of life were included. MRI was normal for 48.2% (95% CI 43.7-52.8). Among infants with brain injuries, 62.5% (95% CI 56.2-68.5) had damage to more than one structure, 19.8% (95% CI 15.0-25.3) showed a pattern-associating injuries of basal ganglia/thalami (BGT), white matter (WM) and cortex. Overall, 68.4% (95% CI 62.0-74.3) of infants with normal MRI survived with a normal neurological examination. The rate of death was 15.4% (95% CI 12.3-19.0), predominantly for infants with the combined BGT, cortex, and/or WM injuries. CONCLUSIONS: Among infants with neonatal encephalopathy treated with hypothermia, two-thirds of those with normal MRI survived with a normal neurological examination at discharge. When present, brain injuries often involved more than one structure. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT02676063). IMPACT: In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge. In total, 10% of newborns showed a pattern associating injuries of the basal ganglia-thalami, white matter, and cortex, which was correlated with a high risk of death at discharge. The evolution of MRI techniques and sequences in the era of hypothermia calls for a revisiting of imaging protocol in neonatal encephalopathy, especially for the timing. The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.

Ovarian torsion: diagnosis, surgery, and fertility preservation in the pediatric population.

Ovarian torsion is rare in the pediatric population. Delayed diagnosis can significantly impact fertility. The aim of this review is to highlight current knowledge regarding clinical presentation, diagnosis, surgical management, and follow-up in the pediatric population. Whilst the presentation is often very unspecific, most children will present with sudden severe unilateral pelvic pain associated with vomiting. A key diagnostic test is pelvic ultrasonography, which may help demonstrate an asymmetric enlarged ovary with peripherally displaced follicles. In the pediatric population, ovarian torsion may occur in a normal ovary. However, underlying lesions can be found in half of cases. Benign neoplasms (teratomas or cystic lesions) represent the commonest etiology, with the risk of malignancy being less than 2%. Surgical management should be focused on fertility preservation. This is achievable through ovarian detorsion ± ovarian cystectomy ± oophoropexy to avoid recurrence. Follow-up studies demonstrate excellent recovery rates of detorsed ovaries including those with ischemic appearances. What is Known: • Ovarian torsion is a rare diagnosis in the pediatric population. • Aspecific symptoms and differential diagnoses lead to missed or delayed diagnosis increasing the risk of oophoprectomy and further infertility. What is New: • Reviewing the latest knowledge about clinical presentation, diagnostic, surgical management, and follow-up of ovarian torsion in the pediatric population. • Adiponectin was negatively associated with diastolic blood pressure and HOMA-IR, and chemerin was negatively associated with glucose.

MRI of the Neonatal Brain: A Review of Methodological Challenges and Neuroscientific Advances.

In recent years, exploration of the developing brain has become a major focus for researchers and clinicians in an attempt to understand what allows children to acquire amazing and unique abilities, as well as the impact of early disruptions (eg, prematurity, neonatal insults) that can lead to a wide range of neurodevelopmental disorders. Noninvasive neuroimaging methods such as MRI are essential to establish links between the brain and behavioral changes in newborns and infants. In this review article, we aim to highlight recent and representative studies using the various techniques available: anatomical MRI, quantitative MRI (relaxometry, diffusion MRI), multiparametric approaches, and functional MRI. Today, protocols use 1.5 or 3T MRI scanners, and specialized methodologies have been put in place for data acquisition and processing to address the methodological challenges specific to this population, such as sensitivity to motion. MR sequences must be adapted to the brains of newborns and infants to obtain relevant good soft-tissue contrast, given the small size of the cerebral structures and the incomplete maturation of tissues. The use of age-specific image postprocessing tools is also essential, as signal and contrast differ from the adult brain. Appropriate methodologies then make it possible to explore multiple neurodevelopmental mechanisms in a precise way, and assess changes with age or differences between groups of subjects, particularly through large-scale projects. Although MRI measurements only indirectly reflect the complex series of dynamic processes observed throughout development at the molecular and cellular levels, this technique can provide information on brain morphology, structural connectivity, microstructural properties of gray and white matter, and on the functional architecture. Finally, MRI measures related to clinical, behavioral, and electrophysiological markers have a key role to play from a diagnostic and prognostic perspective in the implementation of early interventions to avoid long-term disabilities in children. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

Bone Health in Pediatric Patients With Crohn Disease.

OBJECTIVE: The aim of our study was to examine longitudinal changes in bone mineral density (BMD) of children and adolescents with Crohn disease (CD), and risk factors related to low BMD. PATIENTS AND METHODS: All patients ages from 2 to 18 years with CD who underwent dual-energy X-ray absorptiometry (DXA) at diagnosis and at the end of follow-up between 1999 and 2018 were considered for inclusion in this retrospective study. Factors related to changes in BMD at diagnosis and during follow-up were investigated. RESULTS: One hundred and ninety-three patients had the two DXA required. At diagnosis, 36 patients (18.7%) had a low BMD.At the end of follow-up, 31 patients (16%). One hundred and sixty-four patients did not have the two DXA required.In included CD, BMD values were lower in the lumbar spine (LS) than in total body less head (TBLH), as well at diagnosis (P < 0.0001) or at the end of follow-up (P = 0.001).At diagnosis, only growth impairment or low BMI was associated with low BMD (P < 0.0001), only cumulative dose of corticosteroid at the end of follow-up (P = 0.01). CONCLUSION: The high prevalence of low BMD in children and adolescents with IBD highlights the importance of evaluating BMD in these patients at the time of diagnosis and throughout the course of their treatment. Special attention must be given to patients with height delay or low BMI at diagnosis. Long-term glucocorticoid therapy is the main clinical risk factor associated with low BMD at the end of follow-up.

Renal parenchyma impairment characterization in partial unilateral ureteral obstruction in mice with intravoxel incoherent motion-MRI.

Ureteropelvic junction obstruction constitutes a major cause of progressive pediatric renal disease. The biological mechanisms underlying the renal response to obstruction can be investigated using a clinically relevant mouse model of partial unilateral ureteral obstruction (pUUO). Renal function and kidney morphology data can be evaluated using renal ultrasound, scintigraphy and uro-magnetic resonance imaging (uro-MRI), but these methods are poorly linked to histological change and not all are quantitative. Here, we propose to investigate pUUO for the first time using an intravoxel incoherent motion diffusion sequence. The aim of this study was to quantitatively characterize impairment of the kidney parenchyma in the pUUO model. This quantitative MRI method was able to assess the perfusion and microstructure of the kidney without requiring the injection of a contrast agent. The results suggest that a perfusion fraction (f) reduction is associated with a decrease in the volume of the renal parenchyma, which could be related to decreased renal vascularization. The latter may occur before impairment by fibrosis and the findings are in accordance with the literature using the UUO mice model and, more specifically, on pUUO. Further investigation is required before this technique can be made available for the diagnosis and management of children with antenatal hydronephrosis and to select the optimal timing of surgery if required.

High-resolution heavily T2-weighted magnetic resonance imaging for evaluation of the pituitary stalk in children with ectopic neurohypophysis.

BACKGROUND: In anterior pituitary deficiency, patients with non visible pituitary stalk have more often multiple deficiencies and persistent deficiency than patients with visible pituitary stalk. OBJECTIVE: To compare the diagnostic value of a high-resolution heavily T2-weighted sequence to 1.5-mm-thick unenhanced and contrast-enhanced sagittal T1-weighted sequences to assess the presence of the pituitary stalk in children with ectopic posterior pituitary gland. MATERIALS AND METHODS: We retrospectively evaluated the MRI data of 14 children diagnosed with ectopic posterior pituitary gland between 2010 and 2014. We evaluated the presence of a pituitary stalk using a sagittal high-resolution heavily T2-weighted sequence and a 1.5-mm sagittal T1-weighted turbo spin-echo sequence before and after contrast medium administration. RESULTS: A pituitary stalk was present on at least one of the sequences in 10 of the 14 children (71%). T2-weighted sequence depicted the pituitary stalk in all 10 children, whereas the 1.5-mm-thick T1-weighted sequence depicted 2/10 (20%) before contrast injection and 8/10 (80%) after contrast injection (P=0.007). CONCLUSION: Compared with 1.5-mm-thick contrast-enhanced T1-weighted sequences, high-resolution heavily T2-weighted sequence demonstrates better sensitivity in detecting the pituitary stalk in children with ectopic posterior pituitary gland, suggesting that contrast injection is unnecessary to assess the presence of a pituitary stalk in this setting.

EOS microdose protocol for the radiological follow-up of adolescent idiopathic scoliosis.

PURPOSE: Imaging plays a key role in adolescent idiopathic scoliosis (AIS) to determine the prognosis and accordingly define the best therapeutic strategy to follow. Conventional radiographs with ionizing radiation have been associated with 1-2 % increased lifetime risk of developing cancer in children, and physicians, therefore, need a sensitive but harmless way to explore patients at risk, according to the "as low as reasonably achievable" concept. The EOS system (EOS imaging, Paris, France) is available in routine clinical use since 2007, and allows 3D reconstructions of the trunk in standing position with significant radiation reduction. With recent technical advances, further dose reduction can be obtained, but at the cost of image quality that might alter the reliability of 3D reconstructions. The aim of the present study was to analyze the reproducibility of a "microdose" protocol, and evaluate its use in clinical practice. METHODS: 32 consecutive patients followed for AIS were prospectively included. Biplanar radiographs were obtained with the EOS system according to the new microdose protocol. From the microdose images obtained, three experienced operators performed 3D reconstructions, two times for each subject in a random order (total, 192 reconstructions). The intraoperator repeatability and interoperator reproducibility were evaluated, as recommended by the International Organization for Standardization, for the most clinically relevant 3D radiological parameters. RESULTS: The identification of the required anatomical landmarks for the "fast spine" reconstruction process was possible in all cases. None of the patients required a second acquisition for 3D analysis. Mean time for reconstruction was 5 ± 2 min. The intraoperator repeatability was better than interoperator reproducibility for all parameters, with values ranging between 3° and 8° for frontal and sagittal spinal parameters, and between 1° and 8° for pelvic measurements. The agreement was very good for all clinical measurements. No correlation was found between the BMI and the reliability of the measurements. CONCLUSIONS: Because children are notably more sensitive to the carcinogenic effects of ionizing radiation, judicious use of imaging methods and a search for newer technologies remain necessary. Results of the current study show that the new microdose acquisition protocol can be used in clinical practice without altering the quality of the images. Relevant clinical measurements can be made manually, but the landmarks are also visible enough to allow accurate 3D reconstructions (ICC >0.91 for all parameters). The resulting radiation exposure was 5.5 times lower than that received with the prior protocol, corresponding now to a 45-fold reduction compared to conventional radiographs, and can, therefore, almost be considered negligible.

Functional imaging of the human placenta with magnetic resonance.

Abnormal placentation is responsible for most failures in pregnancy; however, an understanding of placental functions remains largely concealed from noninvasive, in vivo investigations. Magnetic resonance imaging (MRI) is safe in pregnancy for magnetic fields of up to 3 Tesla and is being used increasingly to improve the accuracy of prenatal imaging. Functional MRI (fMRI) of the placenta has not yet been validated in a clinical setting, and most data are derived from animal studies. FMRI could be used to further explore placental functions that are related to vascularization, oxygenation, and metabolism in human pregnancies by the use of various enhancement processes. Dynamic contrast-enhanced MRI is best able to quantify placental perfusion, permeability, and blood volume fractions. However, the transplacental passage of Gadolinium-based contrast agents represents a significant safety concern for this procedure in humans. There are alternative contrast agents that may be safer in pregnancy or that do not cross the placenta. Arterial spin labeling MRI relies on magnetically labeled water to quantify the blood flows within the placenta. A disadvantage of this technique is a poorer signal-to-noise ratio. Based on arterial spin labeling, placental perfusion in normal pregnancy is 176 ± 91 mL × min(-1) × 100 g(-1) and decreases in cases with intrauterine growth restriction. Blood oxygen level-dependent and oxygen-enhanced MRIs do not assess perfusion but measure the response of the placenta to changes in oxygen levels with the use of hemoglobin as an endogenous contrast agent. Diffusion-weighted imaging and intravoxel incoherent motion MRI do not require exogenous contrast agents, instead they use the movement of water molecules within tissues. The apparent diffusion coefficient and perfusion fraction are significantly lower in placentas of growth-restricted fetuses when compared with normal pregnancies. Magnetic resonance spectroscopy has the ability to extract information regarding metabolites from the placenta noninvasively and in vivo. There are marked differences in all 3 metabolites N-acetyl aspartate/choline levels, inositol/choline ratio between small, and adequately grown fetuses. Current research is focused on the ability of each fMRI technique to make a timely diagnosis of abnormal placentation that would allow for appropriate planning of follow-up examinations and optimal scheduling of delivery. These research programs will benefit from the use of well-defined sequences, standardized imaging protocols, and robust computational methods.

Periosteum: characteristic imaging findings with emphasis on radiologic-pathologic comparisons.

The periosteum covers most bone structures. It has an outer fibrous layer and an inner cambial layer that exhibits osteogenic activity. The periosteum is a dynamic structure that plays a major role in bone modeling and remodeling under normal conditions. In several disorders such as infections, benign and malignant tumors, and systemic diseases, the osteogenic potential of the periosteum is stimulated and new bone is produced. The newly formed bone added onto the surface of the cortex adopts various configurations depending on the modalities and pace of bone production. Our aim here is to describe the anatomy, histology, and physiology of the periosteum and to review the various patterns of periosteal reaction with emphasis on relations between radiological and histopathological findings. A careful evaluation of the periosteal reaction and appearance of the underlying cortex, in combination with the MRI, clinical, and laboratory data, provides valuable information on lesion duration and aggressiveness, thereby assisting in the etiological diagnosis and optimizing patient management. A solid reaction strongly suggests a benign and slow-growing process that gives the bone enough time to wall off the lesion. Single lamellar reactions occur in acute and usually benign diseases. Multilamellar reactions are associated with intermediate aggressiveness and a growth rate close to the limit of the walling-off capabilities of the bone. Spiculated, interrupted, and complex combined reactions carry the worst prognosis, as they occur in the most aggressive and fast-growing diseases: the periosteum attempts to create new bone but is overwhelmed and may be breached.

Multiparametric optical and MR imaging demonstrate inhibition of tumor angiogenesis natural history by mural cell therapy.

PURPOSE: To determine whether functional imaging using MRI and fibered confocal fluorescence microscopy (FCFM) could be used to monitor cell therapy by mural progenitor cells (MPC). METHODS: Fifty mice bearing TC1 murine xenograft tumors were allocated into: control (n = 17), sham (phosphate buffer saline, n = 16), and MPC-treated (MPC, n = 17) groups. MRI was performed before (D0 ) and 7 days (D7 ) after injection measuring tumor size, R2 * under air, oxygen, and carbogen using blood oxygen level dependent (BOLD) and f (fraction linked to microcirculation), D* (perfusion related coefficient) and Dr (restricted diffusion coefficient) using diffusion-weighted sequences based on the IVIM (intravoxel incoherent motion) method. FCFM was performed at D7 measuring "index leakage" (capillary permeability). RESULTS: Tumor growth was significantly slowed down in the MPC-treated animals (P = 0.002) on D7 . R2 *air significantly decreased in controls between D0 and D7 (P = 0.03), reflecting a decrease in tumor oxygenation. ΔR2 *O2CO2 significantly increased in controls between D0 and D7 (P = 0.01) reflecting loss of vessel response to carbogen. D* significantly decreased in controls between D0 and D7 (P = 0.03). Finally, "index leakage" was lower in the MPC-treated tumors (P = 0,009). CONCLUSION: Treatment by MPC resulted in slowing down of tumor growth, capillary permeability decrease, and stabilization of tumor angiogenesis.

Headache with focal neurologic signs in children at the emergency department.

OBJECTIVE: To identify predictors of secondary headache in children consulting at the pediatric emergency department (ED) for headache with a focal neurologic deficit. STUDY DESIGN: In this prospective cohort study, we enrolled children aged 6-18 years presenting to the ED of a tertiary care hospital with moderate to severe headache and focal neurologic deficit. Enrollment took place between March 2009 and February 2012. Children with a history of trauma, fever, or neurosurgical intervention were excluded from the study. The final diagnosis was made after 1 year of follow-up. Our primary aim was to identify any differences in the frequency of clinical signs between children with a final diagnosis of primary headache and those with a final diagnosis of secondary headache. RESULTS: Of the 101 patients included in the study, 66% received a final diagnosis of primary headache (94% migraine with aura), and 34% received a final diagnosis of secondary headache (76.5% focal epilepsy). On multivariate analysis, children with bilateral localization of pain had a higher likelihood (aOR, 8.6; 95% CI, 3.2-23.2; P<.001) of having secondary headache. CONCLUSION: Among children presenting to the ED with focal neurologic deficits, a bilateral headache location was associated with higher odds of having a secondary cause of headache. Additional longitudinal studies are needed to investigate whether our data can aid management in the ED setting.

Apparent diffusion coefficient measurements of the fetal brain during the third trimester of pregnancy: how reliable are they in clinical practice?

OBJECTIVE: The objective of this study was to determine the reproducibility, the inter-hemispheric difference and the reference apparent diffusion coefficient (ADC) values of the fetal brain according to gestational age. METHOD: One hundred and one normal fetal brain (29.4-38.4 weeks) were analysed with diffusion-weighted MR imaging. ADC was measured in frontal white matter (FWM), occipital white matter (OWM), centrum semi-ovale (CSO), basal ganglia (BG), cerebellar hemisphere (CBM) and pons. ADC ratios (fronto-occipital, fronto-cerebellar and occipito-cerebellar) were calculated. Inter-observer reproducibility was assessed on 27 studies, using intra-class correlation coefficient and Bland-Altman plot. Inter-hemispheric difference was evaluated with Bland-Altman plot. Gestation-specific reference intervals were estimated for each brain region. RESULTS: Inter-observer bias was near zero. Limits of agreement (LOA) were clinically acceptable (-0.17; 0.20 to -0.38; 0.31 × 10(-3) mm(2) /s) for all brain regions except for CSO and pons. Inter-hemispheric bias was near zero. Smallest LOA were for FWM (±0.09 mm(2) /s) and BG (±0.019 mm(2) /s). ADC values decreased, whereas ADC ratio increased with gestational age, reflecting normal maturation. Fronto-occipital, fronto-cerebellar and occipito-cerebellar ratios were consistently above 0.8, 1 and 1, respectively. CONCLUSION: The fetal brain regions with the highest reproducibility and smallest inter-hemispheric differences are the frontal, occipital, cerebellar white matter and BG. ADC ratio could be useful to assess differential temporo-spatial maturation.

Analysis of MRI brain biometrics in fetuses monitored for intra uterine growth restriction and their prognostic value: Results of a prospective multicenter study.

OBJECTIVE: Show a prognostic value of brain changes in fetuses with intra uterine growth restriction (IUGR) on early neonatal outcome. STUDY DESIGN: We prospectively recruited pregnant women whose fetuses presented fetal weight < 5th centile. A brain MRI was performed between 28 and 32 weeks of gestation (WG). Several brain biometrics were measured (as fronto-occipital diameter (FOD) and transverse cerebellar diameter (TCD)). Neonatal prognosis was evaluated according to a composite criterion. RESULTS: Of the 78 patients included, 62 had a fetal brain MRI. The mean centile value of FOD was lower in the unfavorable outcome group (n = 9) compared to the favorable outcome group (n = 53) (24.5 ± 16.8 vs. 8.6 ± 13.2, p = 0.004). The ROC curve for predicting risk of unfavorable neonatal outcome based on FOD presented an area under the curve of 0.81 (95 % CI, [0.63---0.99]) and a threshold determined at the 3rd centile was associated with sensitivity of 0.78 and a specificity of 0.89. In multivariate analysis, a FOD less than the 3rd centile was significantly associated with an unfavorable neonatal risk. There also was a reduction in TCD (25.5 ± 21.5 vs. 10.4 ± 10.4, p = 0.03) in the unfavorable neonatal outcome group. CONCLUSION: We found an association between a reduction in FOD and TCD in fetal MRIs conducted between 28 and 32 WG in fetuses monitored for IUGR with an unfavorable neonatal outcome. Our results suggest that these biometric changes could constitute markers of poor neonatal prognosis.

Quantification of brain-wide vascular resistivity via ultrafast Doppler in human neonates helps early detection of white matter injury.

Preterm birth is associated with cerebrovascular development disruption and can induce white matter injuries (WMI). Transfontanellar ultrasound Doppler is the most widely used clinical imaging technique to monitor neonatal cerebral vascularisation and haemodynamics based on vascular indexes such as the resistivity index (RI); however, it has poor predictive value for brain damage. Indeed, these RI measurements are currently limited to large vessels, leading to a very limited probing of the brain's vascularisation, which may hinder prognosis. Here we show that ultrafast Doppler imaging (UfD) enables simultaneous quantification, in the whole field of view, of the local RI and vessel diameter, even in small vessels. Combining both pieces of information, we defined two new comprehensive resistivity parameters of the vascular trees. First, we showed that our technique is more sensitive in the early characterisation of the RI modifications between term and preterm neonates and for the first time we could show that the RI depends both on the vessel diameter and vascular territory. We then showed that our parameters can be used for early prediction of WMI. Our results demonstrate the potential of UfD to provide new biomarkers and pave the way for continuous monitoring of neonatal brain resistivity.