Immature Brain

Room 701 A


Chairs: Patricia Ellen Grant and Ed X. Wu


Prog #

10:30  666. In Utero MRI Study of Fetal Baboon Brains at 3T

Feng Liu1, 2, Marianne Garland1, Yunsuo Duan1, 2, Raymond Stark1, Dongrong Xu1, 2, Zhengchao Dong1, 2, Ravi Bansal1, 2, Bradley Peterson1, 2, Alayar Kangarlu1, 2

1Columbia University Medical Center, New York, New York, USA; 2New York State Psychiatric Institute, New York, New York, USA

MRI techniques provide a noninvasive tool to study the developing primate brain. We devised a protocol to serially scan pregnant baboons at 3 Tesla for up to 3 hours per session. Seven baboons were scanned beginning as early as 56 days of gestation, to as late as 185 days. Successful scanning of the fetal baboon required careful animal preparation and anesthesia in addition to optimization of the scanning protocol. This protocol will help to advance the use of nonhuman primate models to study fetal brain development longitudinally.

10:42 667. Diffusion Spectrum Imaging (DSI) Tractography of Neonatal Cat Brains

Emi Takahashi1, Guangping Dai1, Ruopeng Wang1, Van J. Wedeen1

1Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts, USA

By diffusion tractography using diffusion spectrum imaging (DSI), we demonstrate and validate the feasibilities of the diffusion tractography in neonatal cat brains, which promises future applications of the technique to pediatric disorders in humans.  We found dramatic structural changes of major white matter tracts during postnatal development.  Particularly, the cingulum bundle increased its length and complexity a lot in the first month of the postnatal development.  We believe that our approach here is fundamental to understand the normal and abnormal formation of cortical gyri related to underlying the white matter structures.

10:54   668.  Framework for Comparing Mutant Mice Against a DTI-Based Normative Atlas of Mouse Brain Development

Jinzhong Yang1, Sajjad Baloch1, Hao Huang1, Sarah Clark1, Paul Yarowsky1,  Susumu Mori1,  Christos Davatzikos1, Ragini Verma, 1, UPenn, Philadelphia, Pennsylvania, USA

In this work we provide a framework for comparing differences between a knockout strain and a normative atlas of the developing mouse brain. We have used Diffusion Tensor Imaging (DTI) in a novel computational neuroanatomy approach to quantify postnatal developmental patterns of C57BL/6J mouse brain and have created a growth and maturation profile of the C57BL/6J mouse, which  is used as a normative brain for several knock-out strains.  This lays the foundation for a normative atlas for a developing brain against which brain anomalies can be quantified. In this work we provide a framework that facilitates such a comparison of neuropathology against the normative baseline. We show the application of this normative atlas in determining growth and maturation abnormalities in a hybrid mouse that has been genetically altered. The framework is general and can be applied to determining changes in mice that have been mutated, at any stage of their development.

11:06 669. Directional Diffusion Kurtosis Analysis of Rat Brain Maturation

Matthew Man Hin Cheung1, 2, Edward Sai Kam Hui1, Ed X. Wu1

1The University of Hong Kong, Pokfulam, Hong Kong

Diffusion Kurtosis Imaging is capable of quantifying the biological tissue complexity. In this experiment, DKI is applied to study the rat brain maturation. The directional kurtoses were found to be highly sensitive to the developmental changes. The restriction in radial direction was found to increase dramatically, probably due to the myelination and other intrinsic axonal factors. The diffusion characteristics and the structural information provided are essential in better understanding of developmental and aging physiology.

11:18  670.  White Matter Alteration in Brain Hemisphere Contralateral to Ligation in Neonatal Rat Model of Hypoxic-Ischemic Injury

Ho-fai Lau1, 2, Jian Yang1, Pek-Lan Khong1, Ed X. Wu1

1The University of Hong Kong, Pokfulam, Hong Kong

Purpose: This study aim to investigate the hypoxic-ischemic (HI) injury in brain hemisphere contralateral to ligation in neonatal rats with DTI. Rats with unilateral left carotid artery ligation were exposed to hypoxic environment for 1 hour (n=9) and 2 hours (n=9) to induce mild and severe HI injuries, respectively. They, together with intact controls (n=11) were longitudinally examined for changes in FA, axial and radial diffusivities. FA decrease and axial diffusivity increase were observed during the acute and subacute stage in the hemispheres contralateral to the ligation when compared to controls.  The findings indicated that WM on seemingly normal contralateral hemisphere was indeed adversely affected, which may impact the long-term brain development after mild or severe HI injury.

11:30 671. Correlation of Neuroinflammatory Molecules Quantified from CSF with Fractional Anisotropy in the Neonatal Meningitis

Rakesh K. Gupta1, Richa Trivedi1, Gyanendra K. Malik2, Abhishek Yadav1, Kashi N. Prasad1, Ram KS Rathore3

1Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 2Chhatrapati Shahuji Maharaj Medical University, Lucknow, India; 3Indian Institute of Technology, Kanpur, India

Diffusion tensor imaging (DTI) was performed on 15 neonates with bacterial meningitis and 10 age/ sex matched controls. Enzyme linked immunosorbent assay was used to quantify neuroinflammatory molecules (sICAM, TNF-á and IL-1â cytokines) in CSF collected on lumber puncture of meningitic neonates. Fractional anisotropy (FA) and mean diffusivity (MD) values were measured by placing region of interests on leptomeningeal corticosubcortical white matter (LCSWM) regions in both patients and controls. Significantly increased FA with no significant change in MD values was observed in patients compared to controls. A significant positive correlation was observed between neuroinflammatory molecules quantified from CSF of patients and FA values collected from LCSWM. Our results suggest that the high FA in LCSWM in neonates with bacterial meningitis reflects the extant of inflammatory response.

11:42  672. Development of Fetus Brain Atlas from Multi-Axial MR Acquisitions

Nicolas Guizard1, 2, Claude Lepage2, Vladimir Fonov2, Helene Hakyemez1, Alan Evans2, Catherine Limperopoulos1

1MCH, Montreal, Canada; 2BIC, Montreal, Canada

Innovative applications of advanced MRI techniques to the high-risk fetus are increasingly providing a powerful tool for the in vivo study of brain development. The ability to reliably acquire 3-D volumetric sequences and to delineate volumetric brain growth in the non-sedated fetus is challenging, but essential for the accurate assessment of the progression of normal and abnormal fetal brain growth in the second and third trimester. The development of a fetal brain atlas would enable a comprehensive and quantitative approach for the study of healthy and high-risk fetal brain growth, and ultimately improve the sensitivity, specificity and prognostic utility of fetal MRI.

11:54  673. DTI Study of Effects of Glucocorticoids on White Matter Development

L Tugan Muftuler1, Orhan Nalcioglu1, Curt Sandman1, Elysia Davis1

1University of California, Irvine, California , USA

The goal of this study was to investigate changes in cerebral white matter morphology among children with prenatal exposure to glucocorticoids. Pregnant woman at risk for premature delivery are routinely administered GCs to promote lung development and survival among premature infants. However, findings from human and animal studies show that exposure to GCs has influence on emotion and stress regulation, cognitive functioning and brain morphology. We have found changes in FA values in white matter in the basal ganglia. The area involved includes a region where AC fibers intermix with striato-pallido and internal pallido subcortical projection fibers.

12:06 674. Fetal Exposure to Bisphenol a Alters Mitochondrial Function

Nicolas Kunz1, Emily J. Camm2, Emmanuel Somm2, Ingrid Kolher1, Stéphane V. Sizonenko2, Michel L. Aubert2, Petra S. Huppi2, Rolf Gruetter1, 3

1Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 2University of Geneva, Geneva, Switzerland; 3University of Lausanne and Geneva, Switzerland

Bisphenol A (BPA; 4,4’-isopropylidenediphenol) has been implicated as an endocrine-disrupting chemical due to its ability to mimic the action of endogenous steroidal hormones resulting in accelerated growth and puberty, reproductive malformations and behavioral modifications. The aim of the project was to evaluate the effect of BPA exposure in the developing rat brain using proton spectroscopy (1H-MRS) at 9.4 Tesla at P20. A significant increase of the Glu/Asp ratio in the hippocampus was detected, which was likely due altered malate-aspartate shuttle activity implicating impaired mitochondrial function.

12:18   675.  Effect of Fetal-Hypoxemia on Neurochemical Profile of Neonate Guinea Pigs During Development

Wen-Tung Wang1, Sang-Pil Lee1, Yafeng Dong1, Carl P. Weiner1, In-Young Choi1

1University of Kansas Medical Center, Kansas City, Kansas, USA

Hypoxia is one of the pregnancy complications that lead to fetal neuro-developmental damage. In this study, 1H MRS was employed to determine whether maternal hypoxia alters neurochemical levels in the neonatal guinea pigs as an adaptive response to the reduced oxygenation before birth. The results show that, while changes in metabolite concentrations happened on postnatal day 0 (P0) in all three regions (hippocampus, striatum, and cerebral cortex), most significant changes happened in the striatum. Further the decrease in Glu on P0 may be associated with delayed or damaged neuronal development due to hypoxia during gestation.