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Biomedical subjects

Guy Sebag

Publications and source records attributed to Guy Sebag.

13 recordsLinked to original sources

Microstructural development of human brain assessed in utero by diffusion tensor imaging.

BACKGROUND: Diffusion-weighted MR imaging (DWI) has been shown to be a great tool to assess white matter development in normal infants. Comparison of cerebral diffusion properties between preterm infants and fetuses of corresponding ages should assist in determining the impact of premature ex utero life on brain maturation. OBJECTIVE: To assess in utero maturation-dependent microstructural changes of fetal cerebral white matter using diffusion tensor MR imaging. MATERIALS AND METHODS: An echoplanar sequence with diffusion gradient (b=700 s/mm(2)) applied in six non-colinear directions was performed between 31 and 37(+3) weeks of gestation in 24 fetuses without cerebral abnormality on T1- and T2-weighted images. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in the white matter. RESULTS: Mean ADC values were 1.8 microm(2)/ms in the centrum semiovale, 1.2 microm(2)/ms in the splenium of the corpus callosum and 1.1 microm(2)/ms in the pyramidal tract. The paired Wilcoxon rank test showed significant differences in ADC between these three white matter regions. Mean FA values were 1.1%, 3.8% and 4.7%, respectively, in the centrum semiovale, corpus callosum and pyramidal tract. A significant age-related decrease in ADC and an increase in FA towards term were demonstrated in the pyramidal tract and corpus callosum. CONCLUSION: Diffusion tensor imaging in utero can provide a quantitative assessment of the microstructural development of fetal white matter. Anisotropic parameters of the diffusion tensor should improve with technical advances.

Anisotropy↗

Lower bone mineral content in children with type 1 diabetes mellitus is linked to female sex, low insulin-like growth factor type I levels, and high insulin requirement.

CONTEXT: Studies on bone mineral characteristics in children with type 1 diabetes mellitus (T1DM) have generated conflicting results. OBJECTIVE: Our objective was to investigate bone mineral characteristics in children with T1DM and to analyze their associations with bone metabolism and the IGF-I system. DESIGN: We recruited a cohort of Caucasian patients with T1DM for at least 3 yr and healthy children between January 2003 and June 2004. SETTING: This was a university hospital-based study. PARTICIPANTS: A total of 127 patients and 319 controls aged 6 to 20 yr participated. METHODS: Dual-energy x-ray absorptiometry was performed in patients and controls. Serum bone alkaline phosphatase, CrossLaps, IGF-I, and IGF-binding protein 3 levels were determined in patients with values analyzed using our normative data from 1150 healthy children. RESULTS: After adjustment for age, sex, pubertal stage, and body mass index sd score, total body bone mineral content (BMC)/lean body mass was significantly lower in patients than in controls (P < 0.04). This difference was a result of the differences between the girls of the two groups. Girls with T1DM had significantly lower lumbar spine and total body BMC than control girls (P = 0.002), whereas no such difference was observed in boys. Serum bone alkaline phosphatase level was significantly lower in girls than in boys (P = 0.04). Low serum IGF-I levels and the administration of large amounts of insulin were found to have independent deleterious effects on BMC for children of all ages and both sexes, whereas disease duration and glycosylated hemoglobin levels did not. CONCLUSIONS: A sex-related difference in the impairment of bone mineral characteristics was identified in children with T1DM. Longitudinal studies are required to investigate whether boys may gain slightly less bone mass during skeletal growth.

Adolescent↗

Abnormal abdominal situs: what and how should we look for?

BACKGROUND: Prenatal management of abnormal abdominal situs is challenging since prognosis is highly variable depending on the associated malformations. METHODS: The authors report on two cases of ambiguous abdominal situs. Prenatal management included specialized ultrasound examination of fetal anatomy and heart, amniocentesis for determination of the fetal karyotype and fetal abdominal MR. RESULTS: In both cases, abnormal situs was associated with other abdominal anomalies such as azygous continuation, biliary atresia, bowel obstruction and polysplenia. Fetal MR was a useful additional tool in the assessment of fetal abdominal anatomy in both cases. CONCLUSIONS: On the basis of these reports, the literature is reviewed and a prenatal management scheme is proposed.

Adult↗

Is there functional vascular information in anatomical MR sequences? A preliminary in vivo study.

According to the type of sequences used, either morphological or dynamic functional study can be performed using magnetic resonance imaging (MRI). The aim of this study is to find out if vascular information found, in dynamic MR sequences, already exists in anatomical MR sequences in the particular case of Legg-Calvé-Perthes disease (LCPD). LCPD is due to a loss of circulation to the femoral head in a growing child resulting in avascular necrosis and leading to possible distortion of size and shape of the proximal femur. MRI acquisitions consist in performing two anatomical sequences and one dynamic sequence with a gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) injection. Five new parametric images characterizing hyper- and hypo-vascularized areas are computed from the dynamic MR sequence. For each new image, the two corresponding anatomical images are found and registered. Then, four types of regions of interest (ROIs) are extracted: healthy hyper- and hypo-vascularized areas and pathological hyper- and hypo-vascularized areas. First-order statistical parameters and texture parameters (Haralick's method, run length method, fractal parameters, autoregressive factors and Laws' texture energy method) are computed in each ROI. Then, a statistical study based on a T test is performed. Results show that some parameters could discriminate the four ROI types. Hence, dynamic vascular image and intrinsic anatomical image characteristics seem to be correlated. Finally, the disease can be evaluated with objective parameters using only anatomical sequences.

Child↗

Contribution of fetal MRI to the diagnosis of inner ear abnormalities: report of two cases.

We report two cases of fetal inner ear abnormalities diagnosed by MRI. Cerebral MRI was performed on two fetuses, at 32 and 30 weeks gestation, following US that demonstrated multiple malformations suggestive of CHARGE syndrome in one fetus and ventriculomegaly and poor visibility of the posterior fossa in the other. MRI revealed vestibular hypoplasia and agenesis of the semicircular canals in one fetus and cystic cochleas, partial vermian agenesis and an occipital meningocele in the second fetus. Both pregnancies were terminated and there was good correlation between fetal MRI, ex utero CT and fetopathological findings. The inner ears should be carefully examined when performing fetal cerebral MRI because abnormalities of the inner ear may be associated with cerebral anomalies.

Abnormalities, Multiple↗

An atypical case of segmental spinal dysgenesis.

Spinal segmental dysgenesis is a complex closed dysraphism. The diagnostic criteria are: lumbar or thoracolumbar vertebral dysgenesis causing kyphosis, focal spinal cord narrowing without exiting roots, deformity of the lower limbs and paraplegia or paraparesis. We present a newborn who showed atypical features of bifocal spinal cord narrowing, without any vertebral abnormality at the proximal level. This seems to be a variant of this rare entity, whose early diagnosis is important, as surgical stabilisation of the spine is required.

Diagnostic Imaging↗

Prenatal diagnosis of horseshoe lung: contribution of MRI.

Horseshoe lung is a very rare pulmonary anomaly that is characterized by an isthmus of lung parenchyma bridging the right and left lungs and extending through the mediastinum. We report on the prenatal diagnosis of such a malformation in a 33-week-gestation fetus. The diagnosis was initially suspected on antenatal ultrasonography performed at 33 weeks and confirmed by fetal MRI and subsequent pathological examination after termination of pregnancy. To our knowledge, this is the first reported case of antenatal diagnosis of horseshoe lung.

Adult↗

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/cm(2)), 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 >or=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.

Absorptiometry, Photon↗

Fetal brain MRI: segmentation and biometric analysis of the posterior fossa.

This paper presents a novel approach to fetal magnetic resonance image segmentation and biometric analysis of the posterior fossa's midline structures. We developed a semi-automatic segmentation method (based on a region growing technique) and tested the algorithm on images of 104 normal fetuses. Using the segmented regions of interest (posterior fossa, vermis, and brainstem), we computed four relative area ratios. Statistical and clinical analysis of our results showed that the relative development of these structures appears to be independent of pregnancy term. In an additional study of 23 pathological cases, one of the four measurements was always significantly different from the corresponding value observed in normal cases.

Algorithms↗

Gestational hypoxia induces white matter damage in neonatal rats: a new model of periventricular leukomalacia.

In the premature infant, periventricular leukomalacia, usually related to hypoxicischemic 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 Sprague-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). Body weight of pups subjected to prenatal hypoxia was 10 to 30% lower from P0 to P14 than in controls. Specific white matter cysts were detected between P0 and P7 in pups subjected to prenatal hypoxia, in addition to abnormal extra-cellular matrix, increased lipid peroxidation, white matter cell death detected by TUNEL, and increased activated macrophage counts in white matter. Subsequently, gliotic scars and delayed myelination primarily involving immature oligodendrocytes were seen. In vivo MRI with T1, T2, and diffusion sequences disclosed similar findings immediately after birth, showing strong correlations with histological abnormalities. We speculate that protracted prenatal hypoxia in rat induces white matter damage occurring through local inflammatory response and oxidative stress linked to re-oxygenation during the perinatal period.

Animals↗

Contribution of fetal MR imaging in the evaluation of cerebral ischemic lesions.

BACKGROUND AND PURPOSE: Little is known about the different patterns of fetal cerebral ischemic lesions at MR imaging. Our purpose was to evaluate the contribution of MR imaging in the evaluation of such lesions by correlating the results with ultrasonography (US) and neurofetopathologic (NFP) findings. METHODS: We examined 28 fetuses (mean, 28 weeks' gestation) with cerebral ischemic lesions on NFP examination. MR findings were correlated with US and NFP results with regard to the depiction of gyration and parenchymal abnormalities. RESULTS: MR imaging added to US findings in 24 cases by revealing lesions (gyration abnormalities, parenchymal lesions). These results were either overlooked during US (n = 16) or more extensive than expected with US (n = 8). MR findings were always confirmed by NFP. NFP yielded additional findings for 14 lesions that were overlooked during MR imaging (n = 4) or that were more extensive than expected with MR imaging (n = 10). T1-, T2-, and T2*-weighted MR patterns of different lesions (cavitations, gliosis, softening of the white matter, laminar necrosis, calcified leukomalacia, old hemorrhage) were identified. CONCLUSION: MR imaging is a valuable tool in the evaluation of fetal brain ischemia. The results of this study emphasize the role of the different sequences (T1-, T2-, T2*-weighted) required to detect fetal cerebral ischemic lesions. MR imaging is more accurate in the detection of small focal lesions than in the evaluation of diffuse white matter abnormalities.

Brain↗

Fetal MRI: normal gestational landmarks for cerebral biometry, gyration and myelination.

PURPOSE: Up until the last 10 years, normal cerebral gestational landmarks were assessed by ultrasonographic and fetopathologic studies. The purpose of this paper is to display the possibilities provided by fetal MRI in the evaluation of fetal cerebral biometry, normal sulcation and myelination. METHODS: Two hundred and twenty-five fetuses (with a normal brain) were studied prospectively using a standardised method. The gestational age ranged from 22 to 38 weeks. The main data concerning biometry of various cerebral structures at those terms are given. DISCUSSION: In contrast to ultrasound, MRI allows measurements of brain (and not skull), which are available independently of the position of the fetal head. The timing of the appearance of the different sulci is also available using MRI. It is considered to be a good marker of fetal brain maturation. The biochemical modifications contemporary to myelination make it possible to evaluate this phenomenon in the fetal brain using MRI.

Aging↗

Patterns of excitotoxin-induced brain lesions in the newborn rabbit: a neuropathological and MRI correlation.

There is pressing need to employ new advances in structural MR brain imaging to better diagnose brain damage in newborn infants. Timely application of such technology will enable improved therapeutic interventions. Diffusion-weighted sequences are a sensitive marker of very early neuronal injury, the spatial pattern of which provides critical information regarding the underlying pathophysiology. We have modified our murine model of excitotoxic neonatal brain injury to the rabbit, an animal whose brain is larger and where the neuroanatomic organization of the subcortical white matter more closely resembles that of the human. Utilizing this rabbit model, we undertook an MRI/histopathologic correlation. We found that as with the mouse, there is a spatiotemporal selectivity to the pattern of brain injury, and that the period from postnatal day (P) 7 to P9 in rabbits corresponds to the time of maximum vulnerability of the brain to excitotoxic white matter damage, which neuropathologically simulates periventricular leukomalacia (PVL). We additionally noted that diffusion-weighted imaging provided the most sensitive means of detecting such lesions and that this method was sensitive to structural maturational changes accompanying the normal cortical ontogeny. Taken together, our findings suggest that this rabbit model of perinatal excitotoxic brain injury will be a valuable addition to experimental approaches to further our understanding of perinatal brain damage, that diffusion-weighted imaging will be an invaluable adjunct to the diagnosis of such injury, and that therapeutic strategies aimed at interrupting the evolution of PVL should include targeting the pathophysiologic cascade induced by excitotoxic neonatal brain injury.

Animals↗