MR Imaging Characteristics and ADC Histogram Metrics for Differentiating Molecular Subgroups of Pediatric Low-Grade Gliomas.

BACKGROUND AND PURPOSE: BRAF and type 1 neurofibromatosis status are distinctive features in pediatric low-grade gliomas with prognostic and therapeutic implications. We hypothesized that DWI metrics obtained through volumetric ADC histogram analyses of pediatric low-grade gliomas at baseline would enable early detection of BRAF and type 1 neurofibromatosis status. MATERIALS AND METHODS: We retrospectively evaluated 40 pediatric patients with histologically proved pilocytic astrocytoma (n = 33), ganglioglioma (n = 4), pleomorphic xanthoastrocytoma (n = 2), and diffuse astrocytoma grade 2 (n = 1). Apart from 1 patient with type 1 neurofibromatosis who had a biopsy, 11 patients with type 1 neurofibromatosis underwent conventional MR imaging to diagnose a low-grade tumor without a biopsy. BRAF molecular analysis was performed for patients without type 1 neurofibromatosis. Eleven patients presented with BRAF V600E-mutant, 20 had BRAF-KIAA rearrangement, and 8 had BRAF wild-type tumors. Imaging studies were reviewed for location, margins, hemorrhage or calcifications, cystic components, and contrast enhancement. Histogram analysis of tumoral diffusivity was performed. RESULTS: Diffusion histogram metrics (mean, median, and 10th and 90th percentiles) but not kurtosis or skewness were different among pediatric low-grade glioma subgroups (P < .05). Diffusivity was lowest in BRAF V600E-mutant tumors (the 10th percentile reached an area under the curve of 0.9 on receiver operating characteristic analysis). There were significant differences between evaluated pediatric low-grade glioma margins and cystic components (P = .03 and P = .001, respectively). Well-defined margins were characteristic of BRAF-KIAA or wild-type BRAF rather than BRAF V600E-mutant or type 1 neurofibromatosis tumors. None of the type 1 neurofibromatosis tumors showed a cystic component. CONCLUSIONS: Imaging features of pediatric low-grade gliomas, including quantitative diffusion metrics, may assist in predicting BRAF and type 1 neurofibromatosis status, suggesting a radiologic-genetic correlation, and might enable early genetic signature characterization.

Third Trimester Structural and Diffusion Brain Imaging after Single Intrauterine Fetal Death in Monochorionic Twins: MRI-Based Cohort Study.

BACKGROUND AND PURPOSE: Single intrauterine fetal death increases the risk of antenatal brain lesions in the surviving twin. We evaluated the prevalence of structural brain lesions, biometry, and diffusivity on routine third trimester MR imaging performed following single intrauterine fetal death. MATERIALS AND METHODS: In a retrospective MR imaging-based cohort study, we compared 29 monochorionic twins complicated with single intrauterine fetal death (14 following laser ablation treatment for twin-to-twin transfusion syndrome, 8 following selective fetal reduction, and 7 spontaneous) with 2 control cohorts (49 singleton fetuses and 28 uncomplicated twin fetuses). All fetuses in the single intrauterine fetal death group underwent fetal brain MR imaging as a routine third trimester evaluation. Structural brain lesions were analyzed. Cerebral biometry and diffusivity were measured and compared. RESULTS: Brain lesions consistent with the evolution of prior ischemic injury were found in 1 of 29 fetuses, not detected by ultrasound. No acute brain infarction, hemorrhage, or cortical abnormalities were found. Supratentorial biometric measurements in the single intrauterine fetal death group were significantly smaller than those in the singleton group, but not significantly different from those in the uncomplicated twin group. There were no significant differences in ADC values of the cerebral hemispheres, basal ganglia, and pons between the single intrauterine fetal death group and either control group. CONCLUSIONS: Although smaller brain biometry was found, normal diffusivity in surviving twins suggests normal parenchymal microstructure. The rate of cerebral structural injury was relatively low in our cohort, arguing against the routine use of fetal brain MR imaging in twin pregnancies complicated with single intrauterine fetal death. Larger prospective studies are necessary to guide appropriate surveillance protocol and parental counseling in twin pregnancies complicated by single intrauterine fetal death.

Neuroimaging Findings in Children with Constitutional Mismatch Repair Deficiency Syndrome.

BACKGROUND AND PURPOSE: Constitutional mismatch repair deficiency is a hereditary childhood cancer predisposition syndrome characterized by brain tumors and colorectal and hematologic malignancies. Our objective was to describe the neuroimaging findings in patients with constitutional mismatch repair deficiency. MATERIALS AND METHODS: This retrospective study included 14 children with genetically confirmed constitutional mismatch repair deficiency who were referred to 2 tertiary pediatric oncology centers. RESULTS: Fourteen patients from 11 different families had diagnosed constitutional mismatch repair deficiency. The mean age at presentation was 9.3 years (range, 5-14 years). The most common clinical presentation was brain malignancy, diagnosed in 13 of the 14 patients. The most common brain tumors were glioblastoma (n = 7 patients), anaplastic astrocytoma (n = 3 patients), and diffuse astrocytoma (n = 3 patients). Nonspecific subcortical white matter T2 hyperintensities were noted in 10 patients (71%). Subcortical hyperintensities transformed into overt brain tumors on follow-up imaging in 3 patients. Additional non-neoplastic brain MR imaging findings included developmental venous anomalies in 12 patients (85%) and nontherapy-induced cavernous hemangiomas in 3 patients (21%). CONCLUSIONS: On brain MR imaging, these patients have both highly characteristic intra-axial tumors (typically multifocal high-grade gliomas) and nonspecific findings, some of which might represent early stages of neoplastic transformation. The incidence of developmental venous anomalies is high in these patients for unclear reasons. Awareness of these imaging findings, especially in combination, is important to raise the suspicion of constitutional mismatch repair deficiency in routine diagnostic imaging evaluation or surveillance imaging studies of asymptomatic carriers because early identification of the phenotypic "gestalt" might improve outcomes.

Can the pattern of vertebral marrow oedema differentiate intervertebral disc infection from degenerative changes?

AIM: To evaluate whether various patterns of bone marrow oedema could be used to discriminate between infection and degenerative change. MATERIALS AND METHODS: Seventy patients with imaging features suspicious for discitis and available clinical follow-up were blindly reviewed for vertebral marrow oedema on sagittal short-tau inversion recovery (STIR) images according to the following patterns: I, vertebra oedema is adjacent to the intervertebral space and sharply-marginated; II, vertebral oedema is adjacent to the intervertebral space but not sharply marginated from normal marrow or involves the entire vertebral body; and III, vertebral oedema is distant from the endplate with intervening hypointense marrow signal. RESULTS: Of 45 patients with a clinical diagnosis of discitis, pattern II was the most common oedema pattern (64%). Approximately 20% and 9% of discitis patients showed patterns I and III, respectively. In patients with degenerative changes, 44% patients showed pattern I, 32% showed pattern II, and 24% showed pattern III. Pattern II had a sensitivity, specificity, and positive predictive value of 0.64, 0.68, and 0.78 for diagnosing spine infection, respectively. CONCLUSIONS: Although bone marrow oedema in infective discitis most often extends from the disc space and has indistinct margins, the oedema may also have sharp margins or be remote from the involved intervertebral space. Bone marrow oedema patterns of infective discitis overlap with those of degenerative disease and are not sufficiently reliable to exclude infection in cases with magnetic resonance imaging findings suggestive of discitis.

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies.

The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.