Study the Cerebral Wall of the Fetal Brain with DTI and Histology
Hao Huang¹, Linda J. Richards², Paul Yarowsky³, Susumu Mori^4
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; ²Queensland Brain Institute, University of Queensland, St. Lucia, Australia; ³Department of Pharmacology and Experimental Therapeutics, University of Maryland, Baltimore, MD, United States; ⁴Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

The cerebral wall of the fetal brain contains multiple layers and undergoes active structural changes during fetal development. DTI imaging can clearly identify three layers in the cerebral wall, which are cortical plate, subplate and inner layer. In this study, we qualitatively and quantitatively characterized the inner layer with both DTI and histology and found that radial structure, rather than the tangential structure of fetal white matter, is dominant in the inner layer during second trimester. Fractional anisotropy values in the inner layer are higher than those in the suplate but lower than those in the cortical plate.

Developing Connectivity in Human Fetal Brains: Emerging Regional Variations
Emi Takahashi¹, Rebecca D. Folkerth², Rudolph Pienaar¹, Albert M. Galaburda³, P. Ellen Grant^1,4
1Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United States; ²Department of Pathology, Children's Hospital Boston, Boston, MA, United States; ³Department of Neurology, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, United States; ⁴Department of Radiology, Massachusetts General Hospital, Boston, MA, United States

Examination of the three-dimensional axonal pathways in the developing brain is key to understanding the formation of cerebral connectivity. Using high-angular resolution imaging (HARDI) tractography, we imaged developing cerebral fiber pathways in human fetal specimens ranged from 18 to 33 post-gestational weeks (W). We observed dominant radial pathways at 18-20W, and at later stages, emergence of short- and long-range cortico-cortical association pathways, subcortical U-fibers in specific brain regions. Although radial pathways still remained, they were less dominant at 33W.  These results demonstrate that HARDI tractography can detect radial migration and emerging regional specification of connectivity during fetal development.

Cortical Folding Analysis for Normal Fetuses
Jue Wu¹, Suyash P. Awate², Daniel Licht³, Catherine Limperopoulos⁴, James C. Gee^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; ²Siemens Corporate Research, Princeton, NJ, United States; ³Children's Hospital of Philadelphia, Philadelphia, PA, United States; ⁴Mcgill University, Montreal, Quebec, Canada

Eight cortical folding measures were applied to T2w in vivo MRIs of 40 normal fetuses with varied gestational ages. Correlations of these measures with gestational age are reported and Gaussian curvature L2 norm and intrinsic curvature index are the two most correlated measures. These measures may be help in characterization of normal neurodevelopment and in detection of abnormal brain growth in fetuses.

3D Fetal Brain Volumetry in Intrauterine Growth Restriction
Mellisa Damodaram^1,2, Lisa Story^1,2, Prachi Patkee¹, Abhilasha Patel^1,2, Amy McGuinness¹, Joanna Allsop¹, Sailesh Kumar, ², Jo Hajnal¹, Mary Rutherford^1
1Robert Steiner MRI Unit, Hammersmith Hospital, Imperial College London, London, United Kingdom; ²Imperial College Healthcare Trust, London, United Kingdom

Fetal intrauterine growth restriction is a significant problem that often results in iatrogenic premature delivery of the fetus. These children may have neurodevelopmental delay and exhibit problems that cannot be explained by the complications of prematurity alone. Little is known about the exact neurostructural deficiencies that arise as a result of intrauterine growth restriction, and MR studies have been limited by difficulties overcoming the inherent problem of fetal motion.  We describe a technique to conduct 3D reconstruction of the fetal brain that enables volumetric analysis of the whole brain and cerebellum in both normally grown and growth restricted fetuses.

Development of Multi-Contrast Human Neonatal Brain Atlas
Kenichi Oishi¹, Pamela Donahue², Lynn Anderson³, Steven Buchthal³, Thomas Ernst³, Andreia Faria¹, Hangyi Jiang^1,4, Xin Li⁴, Michael Miller⁵, Peter van Zijl^1,4, Susumu Mori^1,4, Linda Chang^3
1Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States; ²Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States; ³Neuroscience and Magnetic Resonance Research Program, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI, United States; ⁴F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States; ⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States

We have developed neonatal brain atlases with detailed anatomic information derived from DTI and co-registered anatomical MRI. Combined with a highly elastic non-linear transformation, we attempted to normalize neonatal brain images to the atlas space and three-dimensionally parcellate the images into 122 brain structures. The accuracy level of the normalization was measured by the agreement with manual segmentation. This method was applied to 33 healthy term infants, ranging from 37 to 53 weeks of age since conception, to characterize developmental changes. The future applications for this atlas include investigations of the effect of prenatal events and the determination of imaging biomarkers.

Comparison of Cortical Folding Measures for Evaluation of Developing Cortex
Joshua S. Shimony¹, Jason Hill¹, John Harwell¹, Tim Coalson¹, Dierker Donna¹, Terrie Inder¹, David Van Essen¹, Jeff J. Neil^1
1Washington University in St. Louis, St. Louis, MO, United States

A variety of measures have been proposed to evaluate cortical folding, many of which are based on the mathematical quantity of curvature.  We obtained MRI data from premature infants at <27, 30-31, 34-35, and 38-39 wks postmenstrual age (PMA).  We evaluated how 17 cortical folding measures change with increasing PMA.  There was considerable disparity in the sensitivity of the measures to cortical maturation, though a subset increased in a monotonic and predictable fashion, making them suitable for evaluation of brain development.

Quantification of Tissues’ Maturation in the Infant Brain with Multi-Parametric MRI
Jessica Dubois^1,2, Cyril Poupon^3,4, François Leroy^1,4, Giovanna Santoro¹, Jean-François Mangin^3,4, Lucie Hertz-Pannier^2,5, Ghislaine Dehaene-Lambertz^1,4
1U562, Inserm, Gif-sur-Yvette, France; ²LBIOM, CEA, Gif-sur-Yvette, France; ³LNAO, CEA, Gif-sur-Yvette, France; ⁴IFR49, Paris, France; ⁵U663, Inserm, Paris, France

Brain development proceeds with a specific spatio-temporal pattern across regions during early infancy and childhood. MRI has recently enabled to study this process non-invasively, but the functional significance of MRI indices is still controversial. Here we used multi-parametric quantitative MRI to investigate this issue in the developing brain of 10 healthy infants (age: 6 to 18weeks). Diffusion Tensor Imaging and T1-T2 mappings were performed over the whole brain in a short acquisition time with EPI sequences. The indices quantification highlighted variable age-related changes across different regions of grey and white matter, and specific relationships between indices according to maturational processes.

Gestational Age at Birth Influences Brain White Matter Development
L. Tugan Muftuler¹, Claudia Buss², Orhan Nalcioglu¹, Curt A. Sandman², Elysia Poggi Davis^2
1Center for Functional Onco-Imaging, University of California, Irvine, CA, United States; ²Psychiatry & Human Behavior, University of California, Orange, CA, United States

In the fetal brain, there is minimal myelinated WM at 29 weeks and a dramatic increase is seen after the 36th week. Therefore, this is a period when the brain development is highly vulnerable to insults caused by premature birth. Prior studies have investigated the mean differences between preterm and term children. But the fetal brain development is a continuous process and gestational age at birth will disrupt the process in different phases. Therefore, we studied the persisting effects of GAB on the WM of children. The results show that major WM pathways are strongly influenced by the GAB.

Differences in Biochemical Maturation in Term and Preterm Newborns
Ashok Panigrahy^1,2, Marvin D. Nelson¹, Floyd H. Gilles³, Lisa Paquette⁴, Istvan Seri⁴, Stefan Bluml^1,5
1Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, United States; ²Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States; ³Department of Neuropathology, Children's Hospital Los Angeles, Los Angeles, CA, United States; ⁴Division of Neonatology, Children's Hospital Los Angeles, Los Angeles, CA, United States; ⁵Rudi Schulte Research Institute, Santa Barbara, CA, United States

In this study, we compare age-dependent changes of metabolites using quantitative MR spectroscopy  in white and grey matter of premature neonates without brain injury with normal biochemical maturation in age-matched term neonates. There are subtle but significant differences in the biochemical maturation of white matter in premature infants with normal conventional MR imaging when compared to control term infants. The observations suggest accelerated white matter development in the premature brain possibly from increased sensory-motor stimulation in the extra-uterine environment or possibly a reparative response to subtle brain injury (i.e. possibly related to sepsis induced white matter injury).

The Functional-Structural Interplay During First Two Years' Brain Development
Wei Gao¹, Pew-Thian Yap², Hongtu Zhu³, Kelly Giovanello⁴, Keith Smith², John Gilmore⁵, Weili Lin^6
1Biomedical Engineering, UNC-Chapel Hill, Chapel Hill, NC, United States; ²Radiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States; ³Biostatistics and Biomedical Research Imaging Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States; ⁴Psychology and Biomedical Research Imaging Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States; ⁵Psychiatry, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States; ⁶Radiology and Biomedical Research Imaging Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States

In this study, normal and healthy pediatric subjects aged between 2wk to 2 yrs were studied so as to directly compare the temporal evolution of brain functional and structural connectivity. In so doing, we aim to determine the temporal correlation between functional and structural connectivity during the first two years of life and to reveal whether or not maturation of structural connectivity is needed for functional connectivity.