Thalamocortical Connectivity Predicts Cognition in Children Born Preterm.

Thalamocortical connections are: essential for brain function, established early in development, and significantly impaired following preterm birth. Impaired cognitive abilities in preterm infants may be related to disruptions in thalamocortical connectivity. The aim of this study was to test the hypothesis: thalamocortical connectivity in the preterm brain at term-equivalent is correlated with cognitive performance in early childhood. We examined 57 infants who were born <35 weeks gestational age (GA) and had no evidence of focal abnormality on magnetic resonance imaging (MRI). Infants underwent diffusion MRI at term and cognitive performance at 2 years was assessed using the Bayley III scales of Infant and Toddler development. Cognitive scores at 2 years were correlated with structural connectivity between the thalamus and extensive cortical regions at term. Mean thalamocortical connectivity across the whole cortex explained 11% of the variance in cognitive scores at 2 years. The inclusion of GA at birth and parental socioeconomic group in the model explained 30% of the variance in subsequent cognitive performance. Identifying impairments in thalamocortical connectivity as early as term equivalent can help identify those infants at risk of subsequent cognitive delay and may be useful to assess efficacy of potential treatments at an early age.

T2* relaxometry of fetal brain at 1.5 Tesla using a motion tolerant method.

PURPOSE: The aim of this study was to determine T2* values for the fetal brain in utero and to compare them with previously reported values in preterm and term neonates. Knowledge of T2* may be useful for assessing brain development, brain abnormalities, and for optimizing functional imaging studies. METHODS: Maternal respiration and unpredictable fetal motion mean that conventional multishot acquisition techniques used in adult T2* relaxometry studies are not practical. Single shot multiecho echo planar imaging was used as a rapid method for measuring fetal T2* by effectively freezing intra-slice motion. RESULTS: T2* determined from a sample of 24 subjects correlated negatively with gestational age with mean values of 220 ms (±45) for frontal white matter, 159 ms (±32) for thalamic gray matter, and 236 ms (±45) for occipital white matter. CONCLUSION: Fetal T2* values are higher than those previously reported for preterm neonates and decline with a consistent trend across gestational age. The data suggest that longer than usual echo times or direct T2* measurement should be considered when performing fetal fMRI to reach optimal BOLD sensitivity.

Volumetric cortical loss in sporadic and familial amyotrophic lateral sclerosis.

Patients homozygous for the D90A mutation of the SOD1 gene (homD90A) demonstrate markedly slower progression of disease than those patients with sporadic ALS (SALS). PET studies have demonstrated a different cortical vulnerability in the two groups, reflected also in neurophysiological studies showing reduced cortical excitability in homD90A. Voxel-based morphometric analysis of magnetic resonance images (MRIs) enables the detection of regional differences in grey matter volume, and can be used to localize cortical atrophy in vivo. In this study, segmented, spatially normalized, modulated and smoothed grey matter portions of the MRIs from 23 SALS and seven homD90A patients with similar disability, were compared with those from 28 healthy control subjects. The SALS group showed bilateral areas of atrophy mainly confined to motor and pre-motor cortices. Cortical changes in the homD90A group were more pronounced within the frontal lobes when both were compared with healthy controls. This study provides further evidence for a different pattern of cortical neuronal vulnerability in homD90A versus SALS patients that may provide insight as to their slower rate of disease progression.

Quantification of deep gray matter in preterm infants at term-equivalent age using manual volumetry of 3-tesla magnetic resonance images.

OBJECTIVE: Nonhypothesis-based MRI-analysis techniques including deformation-based morphometry and automated tissue segmentation have suggested that preterm infants at term-equivalent age have reduced tissue volume in the basal ganglia and thalami, which is most apparent among infants with supratentorial lesions. The aim of our study was to test this hypothesis by direct measurement of thalamic and lentiform nuclei volumes in preterm infants at term-equivalent age and term-born controls using manual volumetry. DESIGN/METHODS: Forty preterm infants at term-equivalent age (median gestational age: 29.5 weeks; median birth weight: 1.3 kg) and 8 term-born controls were examined using a 3-T Philips (Best, Netherlands) system. T1-weighted volume images and T2-weighted fast-spin echo pseudovolumes were acquired. There was no significant difference in postmenstrual age at image acquisition between the 2 groups. ImageJ 1.34 (National Institutes of Health, Bethesda, MD) was used for manual segmentations. RESULTS: The median thalamic and lentiform nuclei volumes for preterm infants at term-equivalent age were 13.6 and 3.07 cm3, respectively, significantly smaller than term-control volumes of 16.3 and 5.6 cm3, respectively. Ten preterm infants at term-equivalent age had supratentorial lesions (intraventricular hemorrhage, periventricular leukomalacia, or hemorrhagic parenchymal infarction), and the median thalamic and lentiform volumes for this group were 10.4 and 1.7 cm3, respectively. When this group was excluded, the remaining infants who had mild or moderate diffuse excessive high signal intensity in the white matter on T2-weighted images had a smaller, yet significant, volume reduction compared with controls. Tissue volumes were not related to weight and gestational age at birth. CONCLUSIONS: Manual volumetry confirms that preterm infants at term-equivalent age have reduced thalamic and lentiform volumes compared with controls. This was most marked among infants with supratentorial lesions but was also seen among those with nonfocal white matter abnormalities.

Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography.

Our aim was to investigate the feasibility of studying white matter tracts and connections between the thalamus and the cortex in 2-year-old infants who were born preterm by probabilistic magnetic resonance (MR) tractography. Using this approach, we were able to visualize and quantify connectivity distributions in a number of white matter tracts, including the corticospinal tracts, optic radiations, fibers of the genu and splenium of the corpus callosum, superior longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the distribution within thalamus of fibers connecting to specific cortical regions. In eleven infants with no MR evidence of focal cerebral lesions and appropriate neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped cortical connections to the thalamus that appeared similar to those reported in adults. However, in a proof-of-principle experiment, we examined one further child with marked white matter abnormalities and found that the volume and pattern of thalamo-cortical connections were severely disrupted. This technique promises to be a useful tool for assessing connectivity in the developing brain and in infants with lesions.

Reduced fractional anisotropy on diffusion tensor magnetic resonance imaging after hypoxic-ischemic encephalopathy.

OBJECTIVE: Apparent diffusion coefficients (ADC) that are measured by diffusion-weighted imaging are reduced in severe white matter (WM) and in some severe basal ganglia and thalamic (BGT) injury in infants who present with hypoxic-ischemic encephalopathy (HIE). However, ADC values may pseudonormalize or even be high during this time in some less severe but clinically significant injuries. We hypothesized that fractional anisotropy (FA), a measure of the directional diffusivity of water made using diffusion tensor imaging, may be abnormal in these less severe injuries; therefore, the objective of this study was to use diffusion tensor imaging to measure ADC and FA in infants with moderate and severe hypoxic-ischemic brain injury. METHODS: Twenty infants with HIE and 7 normal control infants were studied. All infants were born at >36 weeks' gestational age, and MRI scans were obtained within 3 weeks of delivery. Data were examined for normality, and comparisons were made using analysis of variance or Kruskal-Wallis as appropriate. RESULTS: During the first week, FA values were decreased with both severe and moderate WM and BGT injury as assessed by conventional imaging, whereas ADC values were reduced only in severe WM injury and some severe BGT injury. Abnormal ADC values pseudonormalized during the second week, whereas FA values continued to decrease. CONCLUSION: FA is reduced in moderate brain injury after HIE. A low FA may reflect a breakdown in WM organization. Moderate BGT injury may result in atrophy but not overt infarction; it is possible that delayed apoptosis is more marked than immediate necrosis, and this may account for normal early ADC values. The accompanying low FA within some severe and all moderate gray matter lesions, which is associated with significant later impairment, may help to confirm clinically significant abnormality in infants with normal ADC values.

Magnetic resonance imaging of muscle in congenital myopathies associated with RYR1 mutations.

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide range of phenotypes, comprising central core disease and distinct subgroups of multi-minicore disease. We report muscle MRI findings of 11 patients from eight families with RYR1 mutations (n=9) or confirmed linkage to the RYR1 locus (n=2). Patients had clinical features of a congenital myopathy with a wide variety of associated histopathological changes. Muscle MR images showed a consistent pattern characterized by (a) within the thigh: selective involvement of vasti, sartorius, adductor magnus and relative sparing of rectus, gracilis and adductor longus; (b) within the lower leg: selective involvement of soleus, gastrocnemii and peroneal group and relative sparing of the tibialis anterior. Our findings indicate that patients with RYR1-related congenital myopathies have a recognizable pattern of muscle involvement irrespective of the variability of associated histopathological findings. Muscle MRI may supplement clinical assessment and aid selection of genetic tests particularly in patients with non-diagnostic or equivocal histopathological features.

T2 relaxation values in the developing preterm brain.

BACKGROUND AND PURPOSE: MR imaging is increasingly used to assess maturation and disease in the preterm brain. Knowledge of the changes in T2 values with increasing postmenstrual age (PMA) will aid image interpretation and help in the objective assessment of maturation and disease of the brain in infants. The aim of this study was to obtain T2 values in the preterm brain from 25 weeks' gestational age (GA) until term-equivalent age in infants who had normal neurodevelopmental findings at a minimum corrected age of 1 year. METHODS: The study group consisted of 18 preterm infants, born at 33 weeks' GA or sooner. The median GA of the infants at birth was 27 weeks (range, 23-33 weeks), and the median PMA at imaging was 31 weeks (range, 25-41 weeks). T2 measurements were obtained using a 1.0-T MR system and a four-echo pulse sequence (TR/TE, 2500/ 30, 60, 110, and 600). T2 values were measured in the thalami, lentiform nuclei, frontal white matter, occipital white matter, and central white matter at the level of the centrum semiovale. RESULTS: A significant negative linear correlation between T2 values and PMA was demonstrated in the lentiform nuclei (P =.003), frontal white matter (P <.0001), occipital white matter (P <.0001), and central white matter at the level of the centrum semiovale (P <.0001). T2 values were not significantly reduced with increasing PMA in the thalami (P =.06). CONCLUSION: T2 values decrease with increasing PMA in the preterm brain.