Publications (47) View all
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Article: Twin-singleton differences in neonatal brain structure.
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ABSTRACT: Twin studies suggest that global and regional brain volumes are highly heritable. However, estimates of heritability vary across development. Given that all twin studies are open to the potential criticism of non-generalizability due to differences in intrauterine environment between twins and singletons, these age effects may reflect the influence of perinatal environmental factors, which are unique to twins and which may be especially evident early in life. To address this question, we compared brain volumes and the relationship of brain volumes to gestational age in 136 singletons (67 male, 69 female) and 154 twins (75 male, 79 female; 82 DZ, 72 MZ) who had received high resolution MRI scans of the brain in the first month of life. Intracranial volume, total white matter, and ventricle volumes did not differ between twins and singletons. However, cerebrospinal fluid and frontal white matter volume was greater in twins compared to singletons. While gray matter volumes at MRI did not differ between groups, the slope of the relationship between total and cortical gray matter and gestational age at the MRI scan was steeper in MZ twins compared to DZ twins. Post-hoc analyses suggested that gray matter development is delayed in MZ twins in utero and that they experience 'catch-up' growth in the first month of life. These differences should be taken into account when interpreting and designing studies in the early postnatal period.Twin Research and Human Genetics 06/2011; 14(3):268-76. · 1.70 Impact Factor -
Article: Prenatal and neonatal brain structure and white matter maturation in children at high risk for schizophrenia.
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ABSTRACT: Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.American Journal of Psychiatry 09/2010; 167(9):1083-91. · 12.54 Impact Factor -
Article: Association of choline levels and tumor perfusion in brain metastases assessed with proton MR spectroscopy and dynamic susceptibility contrast-enhanced perfusion weighted MRI.
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ABSTRACT: While malignant brain tumors typically show high choline concentrations and neovascularity, we have anecdotally noted that a substantial number of brain metastases from lung cancer demonstrate only mildly elevated choline resonances on proton MR spectroscopy ((1)H-MRS). The goals of this study were to determine whether lung cancer metastases are more likely to demonstrate low choline than other metastases and, in addition, to assess the relationship between choline and tissue perfusion in brain metastases. We performed a retrospective analysis of 66 patients with untreated brain metastases (40 NSCLC; 17 breast cancer; 9 melanoma) who underwent multivoxel 2D-CSI (1)H-MRS. Cho/Cr was compared between histologies using Mann-Whitney U tests. Lesions were dichotomized into low and high Cho/Cr groups, and differences in relative Cho/Cr between groups were assessed with Fisher's exact tests. 21 patients also underwent dynamic susceptibility MR perfusion weighted imaging (PWI). Normalized relative cerebral blood volume ratios (rCBV(norm)) were calculated, and strength of correlation between Cho/Cr and rCBV(norm) was assessed. Cho/Cr was significantly lower in lung cancer metastases compared to breast cancer metastases. Cho/Cr < 2.0 was observed in 37.5% of lung cancer metastases, 23.5% of breast cancer metastases, and 0% of melanoma metastases. Lung cancer metastases were significantly more likely to demonstrate low Cho/Cr than melanoma metastases (p = 0.04). There was a strong correlation between Cho/Cr and rCBV(norm) (p = 0.847, p < 0.001), and metastases in the high Cho/Cr group showed significantly higher rCBV(norm). These findings suggest that choline metabolism and tumor perfusion in brain metastases are interrelated, and we posit that this relationship may be due to the influence of the transcription factor HIF-1.Technology in cancer research & treatment 08/2010; 9(4):327-37. · 2.02 Impact Factor -
Article: Evidence on the emergence of the brain's default network from 2-week-old to 2-year-old healthy pediatric subjects.
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ABSTRACT: Several lines of evidence have implicated the existence of the brain's default network during passive or undirected mental states. Nevertheless, results on the emergence of the default network in very young pediatric subjects are lacking. Using resting functional magnetic resonance imaging in healthy pediatric subjects between 2 weeks and 2 years of age, we describe the temporal evolution of the default network in a critical, previously unstudied, period of early human brain development. Our results demonstrate that a primitive and incomplete default network is present in 2-week-olds, followed by a marked increase in the number of brain regions exhibiting connectivity, and the percent of connection at 1 year of age. By 2 years of age, the default network becomes similar to that observed in adults, including medial prefrontal cortex (MPFC), posterior cingulate cortex/retrosplenial (PCC/Rsp), inferior parietal lobule, lateral temporal cortex, and hippocampus regions. While the anatomical representations of the default network highly depend on age, the PCC/Rsp is consistently observed at in both age groups and is central to the most and strongest connections of the default network, suggesting that PCC/Rsp may serve as the main "hub" of the default network as this region does in adults. In addition, although not as remarkable as the PCC/Rsp, the MPFC also emerges as a potential secondary hub starting from 1 year of age. These findings reveal the temporal development of the default network in the critical period of early brain development and offer new insights into the emergence of brain default network.Proceedings of the National Academy of Sciences 05/2009; 106(16):6790-5. · 9.68 Impact Factor -
Article: White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients.
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ABSTRACT: HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter.NeuroImage 05/2009; 47(4):1154-62. · 5.89 Impact Factor
