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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.