Myelin water imaging and R2 * mapping in neonates: Investigating R2 * dependence on myelin and fibre orientation in whole brain white matter.

R2 * relaxation provides a semiquantitative method of detecting myelin, iron and white matter fibre orientation angles. Compared with standard histogram-based analyses, angle-resolved analysis of R2 * has previously been shown to substantially improve the detection of subtle differences in the brain between healthy siblings of subjects with multiple sclerosis and unrelated healthy controls. Neonates, who are born with very little myelin and iron, and an underdeveloped connectome, provide researchers with an opportunity to investigate whether R2 * is intimately linked with fibre-angle or myelin content as it is in adults, which may in future studies be explored as a potential white matter developmental biomarker. Five healthy adult volunteers (mean age [±SD] = 31.2 [±8.3] years; three males) were recruited from Vancouver, Canada. Eight term neonates (mean age = 38.6 ± 1.2 weeks; five males) were recruited from the Children's Hospital of Chongqing Medical University neonatal ward. All subjects were scanned on identical 3 T Philips Achieva scanners equipped with an eight-channel SENSE head coil and underwent a multiecho gradient echo scan, a 32-direction DTI scan and a myelin water imaging scan. For both neonates and adults, bin-averaged R2 * variation across the brain's white matter was found to be best explained by fibre orientation. For adults, this represented a difference in R2 * values of 3.5 Hz from parallel to perpendicular fibres with respect to the main magnetic field. In neonates, the fibre orientation dependency displayed a cosine wave shape, with a small R2 * range of 0.4 Hz. This minor relationship in neonates provides further evidence for the key role myelin probably plays in creating this fibre orientation dependence later in life, but suggests limited clinical application in newborn populations. Future studies should investigate fibre-orientation dependency in infants in the first 5 years, when substantial myelin development occurs.