The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. ...Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors.
Using brain proton magnetic resonance spectroscopic imaging (MRSI) in children with central nervous system (CNS) tumors, we tested the hypothesis that combining information from biologically ...important metabolites, at diagnosis and prior to treatment, would improve prediction of survival. We evaluated brain proton MRSI exams in 76 children (median age at diagnosis: 74 months) with brain tumors. Important biomarkers, choline-containing compounds (Cho), N-acetylaspartate (NAA), total creatine (tCr), lipids and/or lactate (L), were measured at the "highest Cho region" and normalized to the tCr of surrounding healthy tissue. Neuropathological grading was performed using World Health Organization (WHO) criteria. Fifty-eight of 76 (76%) patients were alive at the end of the study period. The mean survival time for all subjects was 52 months. Univariate analysis demonstrated that Cho, L, Cho/NAA and tumor grade differed significantly between survivors and non-survivors (P< or =0.05). Multiple logistic regression and stepwise multivariate Cox regression indicated that Cho + 0.1L was the only independent predictor of survival (likelihood ratio test = 10.27, P<0.001; Cox regression, P=0.004). The combined index Cho + 0.1L was more accurate and more specific predictor than Cho or Cho/NAA. Accuracy and specificity for Cho + 0.1L were 80% and 86%, respectively. We conclude that brain proton MRSI biomarkers predict survival of children with CNS tumors better than does standard histopathology. More accurate prediction using this non-invasive technique represents an important advance and may suggest more appropriate therapy, especially when diagnostic biopsy is not feasible.
To compare the predictive value for adverse outcome of quantitative cerebral lactate level and of apparent diffusion coefficient (ADC) in infants with perinatal asphyxia in the early postnatal ...period.
Lactate-choline ratios determined with proton magnetic resonance (MR) spectroscopy and ADC determined with diffusion MR imaging in basal ganglia and thalami in 26 full-term neonates (age range, 1-10 days) were compared with severity of acute hypoxic-ischemic encephalopathy and long-term clinical outcome. Differences in metabolites between outcome groups were evaluated with the nonparametric Kruskal-Wallis test and the Dunn test. Logistic regression was performed to examine the predictive value of each metabolite for differentiating normal from abnormal or fatal clinical outcome. The likelihood ratio test was used to assess the statistical significance of each metabolite.
Logistic regression confirmed that lactate-choline ratio could be used to differentiate normal (n = 5) from abnormal (n = 14) or fatal (n = 6) outcome (P <.001). The probability of an adverse outcome exceeded 95% for a lactate-choline ratio of 1.0. Even when analyses were restricted to the early postnatal period, lactate-choline ratio was still a significant predictor of adverse outcome (P =.001). Although ADC images were useful in clinical examination of these infants, quantitative ADCs were not predictive of outcome (P =.82).
Higher lactate-choline ratios in basal ganglia and thalami of infants with perinatal asphyxia were predictive of worse clinical outcomes. Absolute ADC in the same brain regions did not indicate a statistically significant relationship with clinical outcome. Cerebral lactate level is useful in identifying infants who would benefit from early therapeutic intervention.
This article highlights the political merit natural sciences were awarded under the totalitarian regime of Nazi Germany and their propagandistic role in Hitler's foreign policy agenda for the ...Balkans, a region which was expected to replace Germany's colonies lost in World War I. It accounts further for the policies and strategies National Socialists used to exert cultural influence on the countries of South-East Europe, namely through a number of institutions with which natural sciences were in one way or another involved in order to promote German culture abroad. The promotion of the German language and, to a certain degree, the Nazi ideology was a precondition for familiarising the Balkan countries with German scientific achievements, which would pave the way for an economic and political infiltration in that region. Therefore, natural sciences, as part of the German intellect, acquired political and economic connotations hidden behind the euphemistic term of cultural policy, designed for this region of geopolitical importance. The article is based almost exclusively on unpublished German records.
Magnetic resonance (MR) spectroscopy provides biochemical information about tumors. The authors sought to determine the relationship between in vivo and ex vivo biochemical characterization of ...pediatric brain tumors by using MR spectroscopy. Their hypothesis was that ex vivo MR spectroscopy provides a link between in vivo MR spectroscopy and neuropathological analysis.
In vivo proton MR spectroscopy was performed before surgery in 11 patients with neuroepithelial tumors. During resection, a total of 40 tumor biopsy samples were obtained from within the volume of interest identified on in vivo MR spectroscopy and were frozen immediately in liquid nitrogen. High-Resolution Magic Angle Spinning (HRMAS) was used to perform ex vivo MR spectroscopy in these 40 tumor biopsy samples. Neuropathological analysis was performed using the same biopsy samples, and the tumors were classified as ependymoma, choroid plexus carcinoma, pineoblastoma (one each), and pilocytic astrocytoma, medullobastoma, low-grade glioma, and glioblastoma multiforme (two each). Ex vivo HRMAS MR spectroscopy improved line widths and line shapes in the spectra, compared with in vivo MR spectroscopy. Choline (Cho) detected in vivo corresponded to three different peaks ex vivo (glycerophosphocholine, phosphocholine PCho, and Cho). Metabolite ratios from in vivo spectra correlated with ratios from ex vivo spectra (Pearson correlation coefficient range r = 0.72-0.91; p < or = 0.01). Metabolite ratios from ex vivo spectra, such as PCho/ total creatine (tCr) and lipid/tCr, correlated with the percentage of cancerous tissue and percentage of tumor necrosis, respectively (r = 0.84; p < 0.001).
Agreement between in vivo and ex vivo MR spectroscopy indicates that ex vivo HRMAS MR spectroscopy can improve resolution of this modality and provide a link between in vivo MR spectroscopy and neuropathological analysis.
Background
Two-dimensional (2-D) shear wave elastography is a new sonographic elastography method for noninvasive measurement of liver stiffness.
Objective
The aim of this study was to establish ...reference values of normal liver stiffness on 2-D shear wave elastography in children.
Materials and methods
Two-dimensional shear wave elastography values were measured in 202 children with no liver disease from the neonatal period to puberty, who were divided into 4 age groups: newborns and infants, preschoolers, elementary school children and adolescents. We investigated the effects of age, depth of elastography measurement, transducer, number of measurements per child, liver size and Doppler parameters of hepatic blood flow on liver elasticity values.
Results
The mean normal liver elasticity value in the study population was: 4.29±0.59 kilopascals (kPa). In neonates and infants, mean liver elasticity value was 4.63 (± 0.6) kPa, in preschoolers and elementary school children, 4.05 (± 0.57) kPa and 4.15 (± 0.52) kPa, respectively, and in adolescents, 4.39 (± 0.55) kPa. Values in neonates and infants as well as adolescents were significantly higher than in preschoolers and elementary school children (Kruskal-Wallis,
P
<0.001; Mann-Whitney
U
tests,
P
<0.05). There was no significant association between liver elasticity values and size of the right lobe or Doppler parameters of hepatic blood flow. Different depths and the number of elastography measurements had no effect on liver elasticity values.
Conclusion
Two-dimensional shear wave elastography is achievable in a wide range of age in children. We established the reference values of normal liver stiffness on 2-D shear wave elastography in children.
Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, ...is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence treatment choice at both initial diagnosis and follow-up, given the inherent difficulties of sequential biopsies to monitor therapeutic response. When combined with anatomical or other types of imaging, MRS provides unique information regarding biochemistry in inoperable brain tumors and can complement neuropathological data, guide biopsies and enhance insight into therapeutic options. The combination of noninvasively acquired prognostic information and the high-resolution anatomical imaging provided by conventional MRI is expected to surpass molecular analysis and DNA microarray gene profiling, both of which, although promising, depend on invasive biopsy. This review focuses on recent data in the field of MRS in children with brain tumors.
Background
Although fibrosis is the main determinant of liver stiffness, other disease-related factors usually disregarded in studies on liver elastography, such as inflammation and cholestasis, may ...influence liver stiffness.
Objective
To evaluate the accuracy of two-dimensional (2-D) shear wave elastography in assessing liver fibrosis in children with chronic liver disease by controlling for the confounding role of several disease- and patient-related factors.
Materials and methods
Three disease groups were studied: 1) various chronic liver diseases, 2) autoimmune hepatitis and 3) biliary atresia. The METAVIR (meta-analysis of histological data in viral hepatitis) score was used for fibrosis staging and grading of necroinflammatory activity. Multiple linear regression was used to evaluate the relationship between liver stiffness measurements and disease-related factors. The diagnostic accuracy of elastography for predicting fibrosis stages was assessed by calculating the area under the receiver operating characteristic curves.
Results
The various chronic liver diseases group (
n
=32; 7.1±4.9 mean±standard deviation years) showed liver stiffness of 8.9±5.0 (mean±standard deviation) kPa, the autoimmune hepatitis group (
n
=33; 8.1±4.4 years) of 7.1±2.7 kPa, and the biliary atresia group (
n
=19; 0.2±0.1 years) of 19.7±15.2 kPa. Liver stiffness measurements differed across METAVIR fibrosis categories in all disease groups. The highest values were found in biliary atresia, at fibrosis stages ≥F2 (F2: 12.4±1.6 kPa, F3: 17.8±2 kPa, F4: 41.5±12.4 kPa). Liver stiffness was strongly associated only with fibrosis (
P
<0.0001) in various chronic liver diseases, but with necroinflammatory activity (
P
<0.0001) and fibrosis (
P
=0.002) in autoimmune hepatitis, and with age (
P
<0.0001), fibrosis (
P
<0.0001) and cholestasis (
P
=0.009) in biliary atresia. Optimal cutoffs for detecting advanced fibrosis (≥F3) were 16 kPa (area under curve: 0.98; sensitivity: 87.5%; specificity: 96.7%) in biliary atresia and 8.7 kPa (area under curve: 0.98; sensitivity: 93.8%; specificity: 96.1%) in other chronic liver diseases.
Conclusion
Two-dimensional shear wave elastography is reliable in assessing liver fibrosis in children with chronic liver diseases.
We evaluated brain abnormalities associated with myelomeningocele in infants.
Between June 1995 and June 2008, 42 patients with myelomeningocele were treated in our hospital. Only 24 patients (13 ...males, 11 females, mean age 1.5 months, range 1 day - 11 months) were evaluated by both spinal and brain magnetic resonance imaging (MRI) and were enrolled in the study.
Brain MRI revealed: hydrocephalus in 21 (87.5%) patients, all of whom required immediate shunting. Total agenesis of the corpus callosum was observed in 2 (8.3%) patients, partial agenesis was seen in 4 (17%) patients and 8 (34%) patients had dysplasia of the corpus callosum. Absence of the septum pellucidum was observed in 2 (8%) patients. Widening of the interhemispheric fissure and colpocephaly were noted in 10 (41%) and in 3 (12%) patients, respectively. Abnormal white matter maturation was observed in 2 (8%) patients. Small posterior fossa was observed in 18 (74%) patients, Chiari malformation in 16 (67%) patients, cerebellar and brain stem hypoplasia in 3 (12%) and 7 (30%) patients, respectively.
MRI examination of the myelomeningocele site is not sufficient. Clinicians should consider obtaining imaging studies of the entire neuraxis in patients with myelomeningocele.
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