Magnetic resonance imaging of the newborn brain: Manual segmentation of labelled atlases in term-born and preterm infants

Abstract

Premature birth is a major and growing problem. Investigations into neuroanatomical correlates and consequences of preterm birth are hampered by complex neonatal brain anatomy and unavailability of atlases and protocols covering the whole brain. We developed delineation protocols for the manual segmentation of cerebral magnetic resonance (MR) images from newborn infants into 50 regions with comprehensive coverage of the brain. We then segmented MR scans from 15 infants born preterm at median 29, range 26–35, weeks postmenstrual age and scanned at term-corrected age, and five term-born infants born at median 41, range 39–45, weeks postmenstrual age. Total and regional brain volumes were estimated in each infant, and regional volumes expressed as a fraction of total brain volume. Total brain volumes were higher with greater age at birth and at time of scan, but once corrected for age at scan there was no difference between preterm and term infants. Fractional age-corrected regional volumes were bigger unilaterally in terms in middle and inferior temporal gyri, anterior temporal lobe, fusiform gyrus and posterior cingulate gyrus. Fractional age-corrected regional volumes were larger in preterms bilaterally in hippocampus, amygdala, thalamus and lateral ventricles, left superior temporal gyrus and right caudate nucleus. These differences were not significant after correcting for multiple hypothesis testing, but suggest subtle differences between preterms and term-borns accessible to regional analysis. Detailed illustrated protocols are made available in the Appendix.

Introduction

Anatomical segmentation, often using atlases, has yielded valuable insights in studies of the adult human brain (Toga and Thompson, 2001, Hammers et al., 2003, Bondiau et al., 2005, Mega et al., 2005, Shattuck et al., 2008). Application of these approaches in the perinatal period could improve the understanding of many problems, such as the effects of preterm birth or perinatal brain injury. However, differences in both brain structure and image characteristics due to rapid growth and myelination changes mean that adult atlases are less able to provide accurate segmentations of the developing brain, particularly so in younger children (Gousias et al., 2008, Gousias et al., 2010). For neonates, new approaches are required (Wilke et al., 2008, Yoon et al., 2009, Faria et al., 2010, Habas et al., 2010a, Habas et al., 2010b, Kuklisova-Murgasova et al., 2011).

The “gold standard” method for segmentation, including tissue classification (Prastawa et al., 2005) and anatomical labelling (Hammers et al., 2003), is manual delineation, which captures anatomical inter-subject variability (Ono et al., 1990). Accurate manual segmentation of anatomical regions of interest requires appropriate protocols which should be published (Bergin et al., 1994). Good protocols guide reproducible slice-by-slice delineations and enable reliable definition of regions of interest (e.g. Ahsan et al., 2007, Hammers et al., 2003).

In this study we defined new delineation protocols suitable for the newborn brain (see Appendix for detailed illustrated protocols). We used them to manually segment volumetric cerebral MR images acquired from both preterm and term-born infants approximately at the normal time of birth (term; 38–42 weeks postmenstrual age). Total and regional brain volumes were estimated based on these segmentations, in order to test two hypotheses: first, that preterm infants have smaller total brain volumes at term‐corrected age; and second, that there are significant differences in the proportional size of neuroanatomical structures in preterm infants compared to term-born controls.