Tina Banks

Multi-centre reproducibility of diffusion MRI parameters for clinical sequences in the brain.

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences.

Normative Development of White Matter Tracts: Similarities and Differences in Relation to Age, Gender, and Intelligence

The white matter of the brain undergoes a range of structural changes throughout development; from conception to birth, in infancy, and onwards through childhood and adolescence. Several studies have used diffusion magnetic resonance imaging (dMRI) to investigate these changes, but a consensus has not yet emerged on which white matter tracts undergo changes in the later stages of development or what the most important driving factors are behind these changes. In this study of typically developing 8- to 16-year-old children, we use a comprehensive data-driven approach based on principal components analysis to identify effects of age, gender, and brain volume on dMRI parameters, as well as their relative importance. We also show that secondary components of these parameters predict full-scale IQ, independently of the age- and gender-related effects. This overarching assessment of the common factors and gender differences in normal white matter tract development will help to advance understanding of this process in late childhood and adolescence.

Neocortical and hippocampal volume loss in a human ciliopathy: A quantitative MRI study in Bardet–Biedl syndrome

Cilia are ubiquitous cell surface organelles with diverse roles from embryogenesis to adult life. The neurodevelopmental functions of the cilium are currently under investigation in animal systems, but relevance to human brain development remains uncertain. We present the first systematic investigation of structural neuroanatomy in a ciliopathy—Bardet–Biedl syndrome (BBS). Qualitative and quantitative aspects of brain structure were evaluated via magnetic resonance imaging in 10 patients with BBS (ages 14–28 years). In comparison to age and gender‐matched healthy controls, BBS patients had significantly reduced total gray matter (GM) volume but no total white matter (WM) or cerebrospinal fluid volume changes. Voxel‐based morphometric analysis indicated regional GM volume loss bilaterally in the anterior temporal lobes and in the medial orbitofrontal cortex, and WM volume loss in the right inferior longitudinal fasciculus. Region‐of‐interest measurements revealed reduced volume of the hippocampus. Two patients were found to have ventriculomegaly. Global GM reduction and regional volume reductions in the temporal lobe may underlie the learning disabilities and behavioral problems experienced by some patients with BBS. These findings are consistent with previous observations in mouse models of BBS, and further implicate the cilium in neurodevelopmental processes relevant to human cognitive function.

Neonatal Hypoxia, Hippocampal Atrophy, and Memory Impairment: Evidence of a Causal Sequence

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohorts HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.

Brain white matter abnormalities in paediatric Gaucher Type I and Type III using diffusion tensor imaging

ObjectiveBiomarkers to monitor neurological dysfunction in Neuronopathic Gaucher disease (NGD) are lacking. Diffusion tensor imaging (DTI) is a technique which allows us to probe the microstructure of the white-matter of the brain, in-vivo. The aim of this study was to investigate the value of DTI to visualise and quantify white matter integrity in children with NGD and Type I Gaucher.DesignDTI was performed and fractional anisotropy (FA), mean diffusivity (MD), axial (λaxial) diffusivity and radial (λradial) diffusivity maps calculated. Tract-based spatial statistics (TBSS) was used to perform a voxel-wise statistical analysis of the main white matter structures compared to age-sex matched control groups.SettingThe study was performed at Great Ormond Street Children’s Hospital NHS TrustPatientsFour NGD and three Type I Gaucher paediatric patients were recruitedResultsThe findings suggest the presence of microstructural white matter changes in NGD patients primarily in the middle cerebellar peduncles compared to an age-sex matched control group. This finding is relevant to the clinical manifestation of ataxia seen in NGD. Diffuse non-specific changes were seen in the Type I patients, but without a focal point.ConclusionsThis study is the first to use DTI to examine the Gaucher brain. While the numbers studied are small, the results suggest that DTI may be an attractive surrogate marker of NGD, worthy of further exploration for use in clinical studies.

Sexual Dimorphism in White Matter Developmental Trajectories Using Tract-Based Spatial Statistics

Abstract Increasing evidence is emerging for sexual dimorphism in the trajectory of white matter development in children assessed using volumetric magnetic resonance imaging (MRI) and more recently diffusion MRI. Recent studies using diffusion MRI have examined cohorts with a wide age range (typically between 5 and 30 years) showing focal regions of differential diffusivity and fractional anisotropy (FA) and have implicated puberty as a possible contributory factor. To further investigate possible dimorphic trajectories in a young cohort, presumably closer to the expected onset of puberty, we used tract-based spatial statistics to investigate diffusion metrics. The cohort consisted of 23 males and 30 females between the ages of 8 and 16 years. Differences in diffusion metrics were corrected for age, total brain volume, and full scale IQ. In contrast to previous studies showing focal differences between males and females, widespread sexually dimorphic trajectories in structural white matter development were observed. These differences were characterized by more advanced development in females compared to males indicated by lower mean diffusivity, radial and axial diffusivity, and higher FA in females. This difference appeared to be larger at lower ages (8–9 years) with diffusion measures from males and females tending to converge between 10 and 14 years of age. Males showed a steeper slope for age-diffusion metric correlations compared to females, who either did not correlate with age or correlated in fewer regions. Further studies are now warranted to determine the role of hormones on the observed differences, particularly in 8–9-year-old children.

To speak, or not to speak? The feasibility of imaging overt speech in children with epilepsy

We systematically compared fMRI results for covert (silent) and overt (spoken) versions of a language task in a representative sample of children with lesional focal epilepsy being considered for neurosurgical treatment (N=38, aged 6-17 years). The overt task was advantageous for presurgical fMRI assessments of language; it produced higher quality scans, was more sensitive for identifying activation in core language regions on an individual basis, and provided an online measure of performance crucial for improving the yield of presurgical fMRI.

Hippocampal damage and Memory Impairment in Congenital Cyanotic Heart Disease

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8‐16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory.