Abstract
Premature infants exhibit widespread insults and delays in white matter maturation that can be sensitively detected early using diffusion tensor imaging. Diffusion tensor tractography facilitates in vivo visualization of white matter tracts and has the potential to be more sensitive than simpler two-dimensional DTI-based measures. However, the reliability and reproducibility of performing tractography for major white matter tracts in preterm infants is not known. The main objective of our study was to develop highly reliable and repeatable methods for ten white matter tracts in extremely low birth weight infants (birth weight ≤1000 g) at term-equivalent age. To demonstrate clinical utility, we also compared fiber microstructural and macrostructural parameters between preterm and healthy term controls. Twenty-nine ELBW infants and a control group of 15 healthy term newborns were studied. A team of researchers experienced in neuroanatomy/neuroimaging established the manual segmentation protocol based on a priori anatomical knowledge and an extensive training period to identify sources of variability. Intra- and inter-rater reliability and repeatability was tested using intra-class correlation coefficient, within-subject standard deviation (SD), repeatability, and Dice similarity index. Our results support our primary goal of developing highly reliable and reproducible comprehensive methods for manual segmentation of 10 white matter tracts in ELBW infants. The within-subject SD was within 1–2% and repeatability within 3–7% of the mean values for all 10 tracts. The intra-rater Dice index was excellent with a range of 0.97 to 0.99, and as expected, the inter-rater Dice index was lower (range: 0.80 to 0.91), but still within a very good reliability range. ELBW infants exhibited fewer fiber numbers and/or abnormal microstructure in a majority of the ten quantified tracts, consistent with injury/delayed development. This protocol could serve as a valuable tool for prompt evaluation of the impact of neuroprotective therapies and as a prognostic biomarker for neurodevelopmental impairments.
Highlights
Diffusion tensor tractography (DTT), a three-dimensional diffusion tensor imaging (DTI) technique, is evolving into a potent investigative tool to study early brain development and white matter structural connectivity in vivo
Tractography results of major white matter fibers obtained from these adult studies were reported to be in agreement with classical definitions based on postmortem studies
Subjects Based on an assessment of image quality and signal abnormalities such as subject motion and geometric distortions, a study population of 29 extremely low birth weight (ELBW) infants was randomly chosen from an imaging cohort of 50 ELBW infants
Summary
Diffusion tensor tractography (DTT), a three-dimensional diffusion tensor imaging (DTI) technique, is evolving into a potent investigative tool to study early brain development and white matter structural connectivity in vivo. Diffusion parameters such as fractional anisotropy (FA) and diffusion coefficients, such as mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD), provide vital insights into the degree of myelination and white matter organization [1,2,3]. The developing neonatal brain has very different tissue characteristics compared to adult brains, such as the degree of myelination and water content, resulting in lower FA values in the white matter tracts [30]. Only a few tracts have been studied, and tractography methodology has not been sufficiently tested for reliability or repeatability in very preterm infants
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