A high percentage of prematurely born children suffer from neurodevelopmental and learning disabilities later in life. To date, few reliable causative or predictive factors have been identified that can be recognized during the early postnatal period and relate to poor outcome in these individuals. White matter injury is commonly identified on magnetic resonance imaging (MRI) studies of prematurely born infants, but the consequences of these lesions on brain morphology and neurodevelopmental outcome has not been reliably determined. Abnormal white matter and related gray matter integrity visible on MRI may result in geometrically quantifiable disturbances from normal brain development, which are detectable in neonatal MRI. We hypothesize that such damage, relating to specific functional abilities and occurring early in development, may be highly focal and anatomically subtle in nature. This project will develop state of the art image analysis techniques specifically to study the developing premature neonatal brain from high resolution MRI data. This is initially aimed at detecting relationships between early brain development and clinical outcome at 30 months, in order to identify consistent anatomical features that predict outcome. Specifically, it will develop techniques to study the two main quantifiable aspects of developmental neuroanatomy: patterns of local and global tissue volume and the resulting patterns of cortical folding. It will combine deformation based morphometric techniques, specialized tissue segmentation algorithms, together with methods of brain surface curvature analysis. New statistical analysis methods will be developed that allow spatial hypothesis free analysis of patterns of tissue growth and surface curvature, in order to detect early focal disturbances in development that predict poor outcome. Finally, we will evaluate these techniques by looking for specific anatomical patterns related to visual and motor outcome abnormalities. Such techniques have a range of applications in the many new in-vivo studies of premature brain anatomy now being performed. They promise to reveal patterns of injury that are potentially avoidable and may allow interventions at early ages when brain plasticity is high. Ultimately, these improvements in our understanding may help to improve developmental outcome.

Public Health Relevance

Premature birth is one of the major causes of childhood neuropsychiatric disorder. This project will develop and apply new methods of detecting brain abnormalities from MRI scans of the premature neonate. The will specifically allow the spatial mapping of patterns of normal and abnormal brain tissue growth after premature birth. These methods will contribute to our understanding of brain development in premature babies and reveal possible new neuronanatomical markers for poor neurological outcome that allow early clinical intervention.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Hirtz, Deborah G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Schools of Medicine
United States
Zip Code
Fogtmann, Mads; Seshamani, Sharmishtaa; Kroenke, Christopher et al. (2014) A unified approach to diffusion direction sensitive slice registration and 3-D DTI reconstruction from moving fetal brain anatomy. IEEE Trans Med Imaging 33:272-89
Seshamani, Sharmishtaa; Cheng, Xi; Fogtmann, Mads et al. (2014) A method for handling intensity inhomogenieties in fMRI sequences of moving anatomy of the early developing brain. Med Image Anal 18:285-300
Studholme, Colin; Rousseau, Francois (2014) Quantifying and modelling tissue maturation in the living human fetal brain. Int J Dev Neurosci 32:3-10
Rousseau, Francois; Oubel, Estanislao; Pontabry, Julien et al. (2013) BTK: an open-source toolkit for fetal brain MR image processing. Comput Methods Programs Biomed 109:65-73
Scott, Julia A; Habas, Piotr A; Rajagopalan, Vidya et al. (2013) Volumetric and surface-based 3D MRI analyses of fetal isolated mild ventriculomegaly: brain morphometry in ventriculomegaly. Brain Struct Funct 218:645-55
Rousseau, Francois; Gounot, Daniel; Studholme, Colin (2013) On high-resolution image estimation using low-resolution brain MRI. Conf Proc IEEE Eng Med Biol Soc 2013:1081-4
Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A et al. (2012) Mapping directionality specific volume changes using tensor based morphometry: an application to the study of gyrogenesis and lateralization of the human fetal brain. Neuroimage 63:947-58
Studholme, Colin (2011) Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping. Annu Rev Biomed Eng 13:345-68
Scott, Julia A; Habas, Piotr A; Kim, Kio et al. (2011) Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI. Int J Dev Neurosci 29:529-36
Tam, Emily W Y; Chau, Vann; Ferriero, Donna M et al. (2011) Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids. Sci Transl Med 3:105ra105

Showing the most recent 10 out of 13 publications