Blaise V. Jones

Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion

OBJECTIVES Neurologic deficits are common after the Norwood procedure for hypoplastic left heart syndrome. Because of the association of deep hypothermic circulatory arrest with adverse neurologic outcome, regional low-flow cerebral perfusion has been used to limit the period of intraoperative brain ischemia. To evaluate the impact of this technique on brain ischemia, we performed serial brain magnetic resonance imaging in a cohort of infants before and after the Norwood operation using regional cerebral perfusion. METHODS Twenty-two term neonates with hypoplastic left heart syndrome were studied with brain magnetic resonance imaging before and at a median of 9.5 days after the Norwood operation. Results were compared with preoperative, intraoperative, and postoperative risk factors to identify predictors of neurologic injury. RESULTS Preoperative magnetic resonance imaging (n = 22) demonstrated ischemic lesions in 23% of patients. Postoperative magnetic resonance imaging (n = 15) demonstrated new or worsened ischemic lesions in 73% of patients, with periventricular leukomalacia and focal ischemic lesions occurring most commonly. Prolonged low postoperative cerebral oximetry (<45% for >180 minutes) was associated with the development of new or worsened ischemia on postoperative magnetic resonance imaging (P = .029). CONCLUSIONS Ischemic lesions occur commonly in neonates with hypoplastic left heart syndrome before surgery. Despite the adoption of regional cerebral perfusion, postoperative cerebral ischemic lesions are frequent, occurring in the majority of infants after the Norwood operation. Long-term follow-up is necessary to assess the functional impact of these lesions.

Diffusion Tensor MR Imaging Reveals Persistent White Matter Alteration after Traumatic Brain Injury Experienced during Early Childhood

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) can noninvasively quantify white matter (WM) integrity. Although its application in adult traumatic brain injury (TBI) is common, few studies in children have been reported. The purposes of this study were to examine the alteration of fractional anisotropy (FA) in children with TBI experienced during early childhood and to quantify the association between FA and injury severity. MATERIALS AND METHODS: FA was assessed in 9 children with TBI (age = 7.89 ± 1.00 years; Glasgow Coma Scale [GCS] = 10.11 ± 4.68) and a control group of 12 children with orthopedic injuries without central nervous system involvement (age = 7.51 ± 0.95 years). All of the subjects were at minimum 12 months after injury. We examined group differences in a series of predetermined WM regions of interest with t test analysis. We subsequently conducted a voxel-wise comparison with Spearman partial correlation analysis. Correlations between FA and injury severity were also calculated on a voxel-wise basis. RESULTS: FA values were significantly reduced in the TBI group in genu of corpus callosum (CC), posterior limb of internal capsule (PLIC), superior longitudinal fasciculus (SLF), superior fronto-occipital fasciculus (SFO), and centrum semiovale (CS). GCS scores were positively correlated with FA in several WM areas including CC, PLIC, SLF, CS, SFO, and inferior fronto-occipital fasciculus (IFO). CONCLUSION: This DTI study provides evidence that WM integrity remains abnormal in children with moderate-to-severe TBI experienced during early childhood and that injury severity correlated strongly with FA.

Magnetic resonance spectroscopy of the pediatric brain.

Proton magnetic resonance (MR) spectroscopy is a complementary method to MR imaging for understanding disease processes in the pediatric brain. By demonstrating the presence of various metabolites in the sampled tissue, MR spectroscopy helps in the understanding of abnormalities detected by MR imaging or clinical examination. This capability is especially pertinent in the pediatric brain, where the manifestation of pathology is superimposed upon a background of normal or abnormal brain development. In this article, we review the major metabolites demonstrated by MR spectroscopy and present examples of MR spectra obtained in various pathological processes encountered in children.

Frequency and spatial characteristics of high-frequency neuromagnetic signals in childhood epilepsy

PURPOSE Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. METHODS Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4,000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Three-dimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. RESULTS Twenty-six patients showed high-frequency (100-1,000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). CONCLUSION The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy.

Anisotropic Diffusion Properties in Infants with Hydrocephalus: A Diffusion Tensor Imaging Study

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) can noninvasively detect in vivo white matter (WM) abnormalities on the basis of anisotropic diffusion properties. We analyzed DTI data retrospectively to quantify the abnormalities in different WM regions in children with hydrocephalus during early infancy. MATERIALS AND METHODS: Seventeen infants diagnosed with hydrocephalus (age range, 0.13–16.14 months) were evaluated with DTI and compared with 17 closely age-matched healthy children (age range, 0.20–16.11 months). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity values in 5 regions of interest (ROIs) in the corpus callosum and internal capsule were measured and compared. The correlation between FA and age was also studied and compared by ROI between the 2 study groups. RESULTS: Infants with hydrocephalus had significantly lower FA, higher MD, and higher radial diffusivity values for all 3 ROIs in the corpus callosum, but not for the 2 ROIs in the internal capsule. In infants with hydrocephalus, the increase of FA with age during normal development was absent in the corpus callosum but was still preserved in the internal capsule. There was also a significant difference in the frequency of occurrence of abnormal FA values in the corpus callosum and internal capsule. CONCLUSIONS: This retrospective DTI study demonstrated significant WM abnormalities in infants with hydrocephalus in both the corpus callosum and internal capsule. The results also showed evidence that the impact of hydrocephalus on WM was different in the corpus callosum and internal capsule.

De Novo Cerebral Arteriovenous Malformation: Case Report and Literature Review

SUMMARY: We describe a rare case of a de novo cerebral arteriovenous malformation (AVM) in a 9-year-old girl. MR imaging at 6 years of age demonstrated band heterotopia. Follow-up MR imaging 3 years later demonstrated a new 3.5-cm AVM in the left parietol-occipital region, confirmed by conventional angiography. This report, along with limited previous reports, suggests that AVMs can be acquired lesions and that AVM development is a dynamic process extending into the postnatal period.

Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination

Mutations in CHD7, encoding ATP-dependent chromodomain helicase DNA-binding protein 7, in CHARGE syndrome lead to multiple congenital anomalies, including craniofacial malformations, neurological dysfunction and growth delay. Mechanisms underlying the CNS phenotypes remain poorly understood. We found that Chd7 is a direct transcriptional target of oligodendrogenesis-promoting factors Olig2 and Smarca4/Brg1 and is required for proper onset of CNS myelination and remyelination. Genome-occupancy analyses in mice, coupled with transcriptome profiling, revealed that Chd7 interacted with Sox10 and targeted the enhancers of key myelinogenic genes. These analyses identified previously unknown Chd7 targets, including bone formation regulators Osterix (also known as Sp7) and Creb3l2, which are also critical for oligodendrocyte maturation. Thus, Chd7 coordinates with Sox10 to regulate the initiation of myelinogenesis and acts as a molecular nexus of regulatory networks that account for the development of a seemingly diverse array of lineages, including oligodendrocytes and osteoblasts, pointing to previously uncharacterized Chd7 functions in white matter pathogenesis in CHARGE syndrome.

Reversible MR imaging and MR spectroscopy abnormalities in association with metronidazole therapy.

We present a report of MRI and proton MR spectroscopy (MRS) findings in an adolescent patient with Down syndrome and Crohn disease treated with metronidazole. MRI revealed signal abnormalities within the corpus callosum, basal ganglia, and brainstem. Proton MRS examination demonstrated a persistent lactate elevation during metronidazole treatment. Clinical, spectroscopic, and imaging abnormalities resolved with discontinuation of metronidazole.

Noninvasive localization of epileptogenic zones with ictal high-frequency neuromagnetic signals

OBJECT Recent reports suggest that high-frequency epileptic activity is highly localized to epileptogenic zones. The goal of the present study was to investigate the potential usefulness of noninvasive localization of high-frequency epileptic activity for epilepsy surgery. METHODS Data obtained in 4 patients, who had seizures during routine magnetoencephalography (MEG) tests, were retrospectively studied. The MEG data were digitized at 4000 Hz, and 3D MR images were obtained. The magnetic sources were volumetrically localized with wavelet-based beamformer. The MEG results were subsequently compared with clinical data. RESULTS The 4 patients had 1-4 high-frequency neuromagnetic components (110-910 Hz) in ictal and interictal activities. The loci of high-frequency activities were concordant with intracranial recordings therein 3 patients, who underwent presurgical evaluation. The loci of high-frequency ictal activities were in line with semiology and neuroimaging in all 4 of the patients. High-frequency epileptic activity was highly localized to the epileptogenic zones. CONCLUSIONS High-frequency epileptic activity can be volumetrically localized with MEG. Source analysis of high-frequency neuromagnetic signals has the potential to determine epileptogenic zones noninvasively and preoperatively for epilepsy surgery.

DTI Values in Key White Matter Tracts from Infancy through Adolescence

BACKGROUND AND PURPOSE: DTI is an advanced neuroimaging technique that allows in vivo quantification of water diffusion properties as surrogate markers of the integrity of WM microstructure. In our study, we investigated normative data from a large number of pediatric and adolescent participants to examine the developmental trends in DTI during this conspicuous WM maturation period. MATERIALS AND METHODS: DTI data in 202 healthy pediatric and adolescent participants were analyzed retrospectively. Fractional anisotropy and mean diffusivity values in the corpus callosum and internal capsule were fitted to an exponential regression model to delineate age-dependent maturational changes across the WM structures. RESULTS: The DTI metrics demonstrated characteristic exponential patterns of progression during development and conspicuous age-dependent changes in the first 36 months, with rostral WM tracts experiencing the highest slope of the exponential function. In contrast, the highest final FA and lowest MD values were detected in the splenium of the corpus callosum and the posterior limb of the internal capsule. CONCLUSIONS: Our analysis shows that the more caudal portions of the corpus callosum and internal capsule begin the maturation process earlier than the rostral regions, but the rostral regions develop at a more accelerated pace, which may suggest that rostral regions rely on development of more caudal brain regions to instigate their development. Our normative DTI can be used as a reference to study normal spatiotemporal developmental profiles in the WM and help identify abnormal WM structures in patient populations.