Understanding brain injury and neurodevelopmental disabilities in the preterm infant: the evolving role of advanced magnetic resonance imaging

Abstract

The high incidence of neurodevelopmental disability in premature infants requires continued efforts at understanding the underlying microstructural changes in the brain that cause this perturbation in normal development. Magnetic resonance imaging (MRI) methods offer great potential to fulfill this need. Serial MR imaging and the application of newer analysis techniques, such as diffusion tensor imaging (DTI), volumetric MR analysis, cortical surface analysis, functional connectivity MRI (fcMRI) and diffusion tractography, provide important insights into the trajectory of brain development in the premature infant and the impact of injury on this developmental trajectory. While some of these imaging techniques are currently available in the research setting only, other measures, such as DTI and brain metric measures can be used clinically. MR imaging also has an enormous potential to be used as a surrogate, short-term outcome measure in clinical studies evaluating new therapeutic interventions of neuroprotection of the developing brain. In this article, we review the current status of these advanced MR imaging techniques.

Fig 1

Conventional T1 weighted images in three premature infants imaged at term. Panel A shows normal white matter maturation; Panel B shows moderate white matter injury with punctate lesions in the periventricular regions and Panel C shows severe white matter injury with a severe reduction in white matter volume and ventriculomegaly.

Fig 2

Diffusion whisker plots overlaid on ADC images from infants of 26 and 35 weeks GA. The line segments are the projection of the major eigenvector onto the plane of the image and represent the orientation of the major eigenvectors. The insets with white borders are magnifications of the parieto-occipital regions of the images. Note that the major axes are oriented radially in cortex at 26 weeks GA. By 35 weeks GA, this feature is much less evident. In both images, organization of whiter matter is visible in the genu of the corpus callosum. The dark areas at the occipital horn of the lateral ventricles of the image from 26 weeks GA is due to small intraventricular hemorrhages layering dependently (with permission McKinstry et al. Oxford University Press).

Fig 3

DTI MR tractography. The colors depict various white matter tracts as follows: Blue - Corpus Callosum genu: Skin color - Corpus Callosum body: Orange color - Corpus Callosum splenium: Green color – Fornix; Pink color - Cingulum;, Yellow color - Corticospinal Tract; and Purple color - Optic Radiations. (Image provided courtesy of Dr. Joshua Shimony, MD; PhD.)

Fig 4

Image segmentation for quantitative volumetric analysis. The image on the left is a coronal T2-weighted image. The image in the center is the corresponding T1-weighted image. The image on the right is the segmentation map derived from these MR images. In this segmentation map components of the brain can be identified as follows: CSF (pink), unmyelinated white matter (taupe), cortical grey matter (blue), basal ganglia (yellow), myelinated white matter (green), and cerebellum (purple).

Fig 5

Standard neonatal brain metric measures in a premature and a term infant. Panel A shows measures in a term infant while Panel B demonstrates a former 30 week infant at term equivalent age. 1: bifrontal diameter; 2a and b: frontal height; 3:biparietal diameter; 4: bone biparietal diameter; 5a,b: cranio-caudal interopercular distance; 6: lateral diameter of the 3^rd ventricle; 7: interhemispheric distance; 8a,b: lateral ventricle diameter; 9: transverse cerebellar diameter.

Fig 6

Serial MR imaging of grey matter gyral maturation in a premature infant on T2 weighted MR images. The image on the left shows immature gyral folding in the left hemisphere of a preterm infant at 30 weeks corrected GA (born at 28 weeks). The center image demonstrates the pattern of folding at 34 weeks and the image on the right shows more mature folding with secondary gyri more consistent with a corrected GA of 38 weeks in the same infant.

Fig 7

fcMRI maps generated using thalamic seed. The images on the left (A) are the average of 28 preterm infants with minimal injury on conventional MRI who underwent fcMRI at term equivalent PMA. The images on the right (B) are the average of 10 term control infants who underwent fcMRI during the first week of life. The colored areas represent regions in which a significant correlation was found between spontaneous fluctuations of the local BOLD signal and those of the thalamic seed. Note the marked difference in thalamo-cortical connectivity between these two data sets. (Images provided courtesy of Dr. Chris Smyser)