Guy Sebag

Magnetic resonance imaging of the fetus

Abstract Fetal magnetic resonance imaging (FMRI) has gained considerable interest during the last decade, especially in its intracranial applications. Due to its high soft-tissue contrast and presumed safety, FMRI should be accepted as a complementary technique in prenatal diagnosis, useful either to elucidate equivocal findings on routine US studies or to further delineate some pathological entities. Normal patterns of fetal brain maturation, as shown by FMRI, are described because they are of paramount importance to accurately evaluate intracranial diseases. To date, however, FMRI requires specialised facilities and should be considered as an evolving clinical research modality and performed within precise guidelines in a multidisciplinary approach to prenatal pathology.

Gestational Hypoxia Induces White Matter Damage in Neonatal Rats: A New Model of Periventricular Leukomalacia

In the premature infant, periventricular leukomalacia, usually related to hypoxic‐ischemic white matter damage, is the main cause of neurological impairment. We hypothesized that protracted prenatal hypoxia might induce white matter damage during the perinatal period. Pregnant Sparague‐Dawley rats were placed in a chamber supplied with hypoxic gas (10% O2 ‐90% N2) from embryonic day 5(E5) to E20. Neonatal rat brains were investigated by histology, immunocytochemistry, western blotting, in situ hybridization, DNA fragmentation analysis, and in vivo magnetic resonance imaging (MRI).

Cerebral biometry in fetal magnetic resonance imaging: new reference data

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.

Metabolic Correction Induced by Leptin Replacement Treatment in Young Children With Berardinelli-Seip Congenital Lipoatrophy

OBJECTIVE. Berardinelli-Seip syndrome is a rare congenital lipoatrophy with a severe prognosis and no efficient therapy. Children present with low leptin levels and severe metabolic complications (insulin resistance, elevated triglyceride levels, and hepatic steatosis). The objective of this study was to test safety and efficacy of recombinant-methionyl-human leptin replacement in children with Berardinelli-Seip syndrome before development of severe metabolic disease METHODS. As part of an open trial, recombinant-methionyl-human leptin was given daily for 4 months to children who did not have diabetes and had Berardinelli-Seip congenital lipoatrophy and metabolic complications at a dosage that was meant to achieve physiologic levels. Six boys and 1 girl (age: 2.4–13.6 years), with a mean fasting insulin level of >15 mIU/L and hypertriglyceridemia, were included. RESULTS. At the end of the recombinant-methionyl-human leptin treatment, a 63% reduction of fasting triglycerides level was achieved. A simultaneous 30% increase in insulin sensitivity was seen, and liver volume was reduced by 20.3%. More remarkable, values of insulin sensitivity and triglyceride level were in the reference range in 4 patients. CONCLUSIONS. Leptin replacement is able to reverse metabolic complications in the majority of children with Berardinelli-Seip congenital lipoatrophy and with insulin resistance or dyslipidemia before the development of overt diabetes.

Femoral head vascularisation in Legg-Calvé-Perthes disease: comparison of dynamic gadolinium-enhanced subtraction MRI with bone scintigraphy

AbstractBackground. It has been reported that MRI using a dynamic gadolinium-enhanced subtraction technique can allow the early identification of ischaemia and the pattern of revascularisation in Legg-Calvé-Perthes (LCP) disease with increased spatial and contrast resolution. Therefore, dynamic gadolinium-enhanced subtraction (DGS) MRI may be a possible non-ionising substitute for bone scintigraphy. Objective. The purpose of this prospective study was to compare DGS MRI and bone scintigraphy in the assessment of femoral head perfusion in LCP disease. Materials and methods. Twenty-six DGS MR images and bone scintigraphies of 25 hips in 23 children were obtained at different stages of LCP disease; three stage I, 12 stage II, six stage III and five stage IV (Waldenström classification). The extent of necrosis, epiphyseal revascularisation pathways (lateral pillar, medial pillar, and/or transphyseal perfusion) and metaphyseal changes were analysed. Results. Total agreement between both techniques was noted in the depiction of epiphyseal necrosis (kappa=1), and metaphyseal abnormalities (kappa=0.9). DGS MRI demonstrated better revascularisation in the lateral (kappa=0.62) and medial pillars (kappa=0.52). The presence of basal transphyseal reperfusion was more conspicuous with MRI. Conclusions. DGS MRI allows early detection of epiphyseal ischaemia and accurate analysis of the different revascularisation patterns. These changes are directly related to the prognosis of LCP disease and can aid therapeutic decision making.

Dynamic gadolinium-enhanced subtraction MR imaging – a simple technique for the early diagnosis of Legg-Calvé-Perthes disease: preliminary results

Purpose. To determine whether the simple technique of dynamic gadolinium-enhanced subtraction MR imaging, which is available on standard MR units, can detect ischemia of the femoral head in children with early Legg-Calvé-Perthes disease (LCP). Materials and methods. Bone perfusion of eight hips in four patients (mean age 7.5 years) was studied using dynamic gadolinium-enhanced subtraction MR imaging at the onset of proven LCP (with initial negative plain films). Enhancement of subtracted images was compared with that on standard MR images and with bone scintigraphy find- ings. Results. Subtraction MR imaging depicted ischemia as a widespread absence of enhancement and was in good agreement with bone scintigraphy. The subtraction technique improved the sensitivity and the specificity of MR imaging in two children. Furthermore, subtraction MR imaging allowed recognition of the pattern of early reperfusion. Conclusion. Our preliminary results indicate that dynamic gadolinium-enhanced subtraction MRI is a simple and promising means of early recognition of ischemia in LCP.

Ultrasonography of Crohn disease in children.

US is increasingly performed in Crohn disease (CD) in children as a first line imaging modality. It reduces the use of other more invasive examinations such as endoscopy, CT or contrast enema. We describe bowel ultrasonography technique, normal bowel appearances on US and pathological patterns in CD. We discuss the current role and limitations of bowel US in CD in children including diagnosis, extent of disease, assessment of disease activity, follow-up and detection of complications. The diagnostic accuracy of US is discussed according to the literature and compared to other imaging modalities. US is currently used for screening in children with the suspicion of inflammatory bowel disease (IBD) with a good negative predictive value. In follow-up, US has a role in monitoring medical treatment by evaluating disease activity, extent of disease and for detecting complications.

Brain iron levels in attention-deficit/hyperactivity disorder: a pilot MRI study.

Abstract Objective. Brain iron deficiency has been supposed to be involved in the pathophysiology of ADHD. Available studies assessing iron in ADHD are based on serum ferritin, a peripheral marker of iron status. To what extent serum ferritin correlates with brain iron (BI) is unclear. The main aim of this study was to compare BI, estimated with magnetic resonance imaging (MRI) in the putamen, pallidum, caudate, and thalamus, between children with and without ADHD. The secondary aim was to assess the correlation between serum ferritin and BI levels. Methods. Thirty-six children (18 with and 18 without ADHD, the latter including nine healthy controls and nine psychiatric controls) completed MRI and blood sampling. Brain iron levels were estimated by imaging T2*. Results. Children with ADHD showed significantly lower estimated BI in right and left thalamus compared to healthy controls. Estimated BI did not differ significantly between children with ADHD and psychiatric controls. Children with ADHD had significantly lower levels of serum ferritin than healthy as well as psychiatric controls. Serum ferritin and T2* values did not correlate significantly in most regions. Conclusions. Low iron in the thalamus may contribute to ADHD pathophysiology.

Improvement in Bone Mineral Density and Body Composition in Survivors of Childhood Acute Lymphoblastic Leukemia: A 1-Year Prospective Study

Objectives. Abnormalities in bone mineral density (BMD), body composition, and bone metabolism have been reported in children who were treated for acute lymphoblastic leukemia (ALL) during and after completion of therapy. However, these studies are cross-sectional, and no longitudinal data are available in a large group of patients after completion of therapy. In the present study, 1-year longitudinal changes in BMD, body composition, and bone metabolism were evaluated in children with ALL during the first 3 years after completion of therapy without cranial irradiation. Methods. BMD of total body (TB; g/cm2), areal and apparent volumetric lumbar spine (L2–L4), lean body mass, and percentage of body fat were measured by dual-energy x-ray absorptiometry in 37 children (median age: 7.9 years; range: 4.7–20.6 years) who were treated for ALL at a median age of 3.3 years (range: 1.1–16.6 years), after a median time of 2.2 years after the completion of treatment, and after a 1-year follow-up period. Two control subjects (n = 74) who were matched for gender, age, and pubertal stage were also longitudinally investigated for body composition for 1 year. Usual serum biochemical markers of calcium metabolism and bone turnover were measured in patients during the study period. Results. A slight decrease in TB BMD was found after a median time of 2.2 years after the completion of therapy for ALL in childhood. Patients showed a significantly lower median TB BMD when evaluated <1.5 years as compared with those at ≥1.5 years since completion of therapy. At the time of first evaluation, the percentage of body fat mass was significantly higher and patients were physically less active than their matched control subjects. Although, as expected, during the 1 year of follow-up both groups showed an annual increment in their BMD measurements, a significantly higher increase in TB BMD was observed in patients in comparison with control subjects. During this same period, the increase in the percentage of body fat mass was slightly lower in ALL patients as compared with control subjects. At the end of the follow-up year, BMD, body-composition parameters, and physical activity of ALL patients were similar to those observed in matched control subjects. Serum biochemical markers of bone turnover were normal at both evaluations. Conclusions. A significant increase in TB BMD and a tendency to a lesser increase in percentage of body fat mass were observed during the study period in ALL patients as compared with chronological age-, gender-, and pubertal stage–matched control subjects. These findings suggest a positive effect of long-term completion therapy and increase in physical activity on BMD, body composition, and bone metabolism in patients who have been treated for ALL.

Contribution of Diffusion-Weighted Imaging in the Evaluation of Diffuse White Matter Ischemic Lesions in Fetuses: Correlations with Fetopathologic Findings

BACKGROUND AND PURPOSE: The sensitivity of fetal MR imaging is poor with regard to the evaluation of diffuse ischemic white matter (WM) abnormalities. Our purpose was to evaluate the contribution of diffusion-weighted imaging (DWI) in the analysis of microstructural changes in WM and to correlate neuroimaging with neurofetopathologic findings. MATERIALS AND METHODS: We included fetuses with MR imaging, DWI, and a fetopathologic examination. In a region of interest defined by MR imaging, where T1 and T2 intensities were abnormal, the apparent diffusion coefficient (ADC) was measured and immunohistochemical analysis was performed. In fetuses with no WM abnormality in signal intensity, region of interest was defined at random. Histologic reading was performed with a complete blinding of the MR imaging results and ADC values. Three degrees of histologic appearance were defined with regard to vasogenic edema, astrogliosis, microgliosis, neuronal and oligodendrocytic abnormalities, and proliferation or congestion of vessels and were compared with a χ2 test in groups A (normal ADC) and B (increased ADC) fetuses. RESULTS: We included 12 fetuses in group A and 9 in group B, ranging from 29 to 38 weeks of gestation. All group B fetuses and 1 group A fetus demonstrated WM abnormalities in signal intensity. WM edema and astrogliosis were more common in group B than in group A (7/9 vs 2/12 and 8/9 vs 4/12, respectively). No significant difference was observed between both groups with regard to the other parameters. CONCLUSION: This study showed a strong correlation between increased ADCs and 1) WM abnormalities in signal intensity on MR imaging, and 2) vasogenic edema with astrogliosis of the cerebral parenchyma.