Isolated mild ventriculomegaly (IMVM) is one of the most frequent diagnoses made on routine prenatal ultrasound. Despite its relatively common occurrence, the neurodevelopmental outcome of fetuses diagnosed with IMVM on prenatal ultrasound cannot be accurately determined. Indeed, studies to date indicate that anywhere from 0% to 36% of fetuses will develop neurodevelopmental disabilities during infancy or childhood, making prenatal counseling extremely challenging and frustrating for clinicians. Recent technical advances in fetal magnetic resonance (MR) imaging have resulted in improved visualization of the fetal brain compared with prenatal ultrasound. As such, fetal MR imaging offers the ability to more closely and non-invasively study both macrostructural and microstructural changes during in utero brain development. The health relatedness of this proposal is to improve prenatal counseling through advances in fetal MR imaging and to prenatally identify those fetuses at higher risk for neurodevelopmental disabilities so that patients can benefit from earlier postnatal treatment interventions. The central hypotheses of this proposal are that fetuses with IMVM have abnormalities in brain development, the abnormalities can be assessed by fetal MR imaging, and that these abnormalities correlate with neurodevelopmental outcome.
The Specific Aims are 1) to characterize microstructural changes in the developing white matter of fetuses with IMVM, 2) to identify macrostructural abnormalities in fetuses with IMVM, and 3) to correlate MR imaging markers from Specific Aims 1 and 2 with neurodevelopmental outcome at 12 and 30 months of age. The broad, long-term objectives are to better understand the etiology and pathogenesis of IMVM;to identify imaging parameters that can be used to better predict neurodevelopmental outcome;and to translate this knowledge into improved prenatal counseling, early treatment intervention during infancy, and future studies on the prevention and treatment of IMVM.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
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NST-2 Subcommittee (NST)
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Hirtz, Deborah G
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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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
Glenn, Orit A; Cuneo, Addison A; Barkovich, A James et al. (2012) Malformations of cortical development: diagnostic accuracy of fetal MR imaging. Radiology 263:843-55
Habas, Piotr A; Scott, Julia A; Roosta, Ahmad et al. (2012) Early folding patterns and asymmetries of the normal human brain detected from in utero MRI. Cereb Cortex 22:13-25
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
Scott, Julia A; Hamzelou, Kia S; Rajagopalan, Vidya et al. (2012) 3D morphometric analysis of human fetal cerebellar development. Cerebellum 11:761-70
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
Jacob, Francois Dominique; Habas, Piotr A; Kim, Kio et al. (2011) Fetal hippocampal development: analysis by magnetic resonance imaging volumetry. Pediatr Res 69:425-9
Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A et al. (2011) Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero. J Neurosci 31:2878-87
Berman, J I; Hamrick, S E G; McQuillen, P S et al. (2011) Diffusion-weighted imaging in fetuses with severe congenital heart defects. AJNR Am J Neuroradiol 32:E21-2
Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A et al. (2011) Spatiotemporal morphometry of adjacent tissue layers with application to the study of sulcal formation. Med Image Comput Comput Assist Interv 14:476-83

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