Normal myelination

After normal myelination in utero, myelination of the neonatal brain is far from complete. The first myelination is seen as early as the 16^th week of gestation, in the column of Burdach, but only really takes off from the 24^th week ¹. It does not reach maturity until 2 years or so. It correlates very closely to developmental milestones ³. The progression of myelination is predictable and abides by a few simple general rules; myelination progresses from:

1. central to peripheral
2. caudal to rostral
3. dorsal to ventral
4. sensory then motor

T1 myelination milestones⁶

• term birth:
  • dorsal brainstem
  • posterior limb internal capsule
  • perirolandic gyri
• 3-4 months:
  • ventral brainstem
  • anterior limb internal capsule
  • splenium of corpus callosum
  • central, posterior corona radiata
• 6 months:
  • cerebellar white matter
  • genu of corpus callosum
  • parietal, occipital white matter
• 12 months:
  • posterior fossa (~adult)
  • most of corona radiata
  • posterior subcortical white matter
• 18 months:
  • all white matter except temporal, frontal U-fibers
• 24 months:
  • anterior temporal, frontal U-fibers

T2 myelination milestones⁶

• term birth: 
  • dorsal brainstem
  • partial posterior limb internal capsule
  • perirolandic gyri
• 3-4 months:
  • posterior limb internal capsule
• 6 months:
  • ventral brainstem
  • anterior limb internal capsule
  • splenium of corpus callosum
  • occipital white matter
• 12 months:
  • most of corona radiata
  • posterior subcortical white matter
• 18 months:
  • all white matter except temporal, frontal U-fibers, occipital radiations
• 24 months:
  • anterior temporal, frontal U-fibers

White matter myelination by location⁷

• centrum semiovale: T1 at 2-4 months, T2 at 7-11 months
• occipital white matter:
  • deep: T1 at 3-5 months, T2 at 9-14 months
  • subcortical: T1 at 4-7 months, T2 at 11-15 months
• mid-frontal white matter:
  • deep: T1 at 3-6 months, T2 at 11-16 months
  • subcortical: T1 at 7-11 months, T2 at 14-18 months
• anterior frontal white matter:
  • deep: T1 at 5-8 months, T2 at 12-18 months
  • subcortical: T1 at 10-15 months, T2 at 24-30 months

Radiographic features

CT

Unmyelinated white matter is hypodense compared to normal white matter and grey matter.

MRI

• T1:
  • most sensitive sequence in children <1 year of age ¹
  • myelination represented by T1 hyperintensity
• T2
  • most sensitive sequence in children between the age of 1 and 2 demonstrating gradual shift from hyper- to hypo-intense relative to grey matter
  • the only area to remain hyperintense after the age of 2 years, and often for quite some time, is the peritrigonal region ⁴ which is called terminal zones of myelination
  • differentiation between terminal zones and PVL requires detection of normally myelinated white matter between the patchy hyperintense T2 signal and the lateral ventricle
• FLAIR
  • unsurprisingly follows the same pattern as T2 but lags behind somewhat. The exception is deep cerebral white matter, which begin as heterogenously hypointense during the first few months of life. 
  • this area then joins the remainder of white matter as hypointense before finally once more becoming hypointense in the second year of life ²
• proton density: 
  • PD weighted images are useful in distinguishing gliosis from hypomylination

In the acute setting DWI is more sensitive than either T1 or T2. 

Fractional anisotropy (FA) increases with brain maturation (diffusion is restriced perpendicular to the direction of axons, thus the increase in DWI signal in large axon bundles running through the slice, e.g posterior limb of interal capsule)

MR spectrocopy demonstrates elevated myoinositol and choline in neonates which gradually declines. Myoinositol decreases to adult values by end of first year and choline by 2-3 years. NAA increases with myelination (in the first year of life).