Three‐dimensional visualization of fetal white‐matter pathways in utero

Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that probes the threedimensional (3D) tissue architecture by measuring the directionality and amount of motion of water molecules. In the brain, bundles of unmyelinated axons create a strongly anisotropic environment with a diffusion maximum parallel to the orientation of the fiber tracts. Computational postprocessing algorithms use the directional diffusion information of each imaged voxel to generate 3D visualized ‘fibers’. This noninvasive computational technique – ‘tractography’ – thus allows the 3D reconstruction and depiction of main white-matter fiber pathways1,2. Tractography has already been used to identify white-matter fiber tracts in healthy adults3, children and adolescents4, newborns5 and preterm newborns6, as well as in postmortem samples of fetal brains7–9. So far there has been only one published study that used DTI-based tractography to delineate whitematter fiber tracts in a clinical fetal MRI setting. Using specially tailored DTI sequences10, our group was able to successfully delineate both sensorimotor tracts and the corpus callosum in living unsedated fetuses in utero and to compare developmental changes in the morphology of these fiber tracts across gestational age. Apart from the large commissural and projection fiber tracts (Figure 1a), DTI-based tractography can also identify smaller fiber bundles in the living unsedated fetus in utero during a routine fetal MRI examination. As an example we present here the case of a 33-week fetus with normal brain development that was examined at our institution using a 1.5T MRI scanner (Philips, Best, The Netherlands) and a DTI sequence with 16 gradient encoding directions and a reconstructed voxel size of 0.94 × 0.94 × 3 mm. Based on their different course and destination, the internal capsule fibers could be further separated: thalamocortical fibers branch off to enter the thalamus, while corticopontine and corticospinal tracts continue and enter the cerebral peduncles (Figure 1b). Within the thalamocortical fiber system anterior, superior and posterior thalamic radiations could be distinguished, projecting through the internal capsule towards frontal, central and posterior cortical regions, respectively3. In addition to projection and thalamic fibers, which connect the cortex to subcortical structures, and commissural fibers that cross to the contralateral hemisphere, association fiber tracts connecting ipsilateral cortical areas were also successfully visualized (Figure 1c). The latter are essential for the integrative function of specialized cortical areas, and their damage can lead to disconnection syndromes resulting in diverse neuropsychological deficits11. The current potential of in utero DTI to visualize the variety of described white matter pathways and their topographical 3D relationship is illustrated in Figure 1d. We consider DTI-based tractography to be a very promising addition to standard fetal MRI protocols, as it will improve our understanding of fetal subcortical brain architecture and development, and has the potential to acquire diagnostic information in cases of suspected pathology12.