Quantitative Characterization of Radiation Dose Dependent Changes in Normal- Appearing White Matter of Cerebral Tumor Patients Using Diffusion Tensor Imaging

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 8, 2006

Presenter: V. Nagesh
Presenter's Affiliation: University of Michigan, Ann Arbor, MI
Type of Session: Plenary


  • Radiation effects on normal brain tissue can include neuroinflammation, demyelination, disruption of the blood-brain barrier, cerebral edema, and white matter necrosis.
  • Hypothesis: Radiation causes demyelination and structural degradation in normal appearing white matter (NAWM).

Materials and Methods

  • 20 patients with malignant glioma, low grade astrocytoma, and benign conditions
  • Radiation: median dose, 67 Gy
  • Imaging:
    • Diffusion tensor imaging using MRI was used before radiation, during radiation (at 1 week, 3 weeks, and at 6 weeks), and after radiation (1 month, 3 months, and 6 months after completion of RT)
    • Principle: MRI can image the diffusion of protons in water. In a neuron, water preferentially diffuses along the length of the axon (parallel) rather than in the radial direction (perpendicular), because it is blocked by the myelin sheath.
    • Demyelination would increase the amount of perpendicular diffusion compared to parallel diffusion because the myelin sheath would no longer block the water diffusion.
  • The genu of the corpus callosum was selected as a site of NAWM because all the fibers run in the same direction.
  • The "fractional anisotropy" (FA) is the ratio of parallel to perpendicular diffusion. A high FA indicates an intact, myelinated neuron. A low FA is a sign of demyelination.


  • 1 month following radiation, there was evidence of demyelination (FA decreased 14%).
  • After radiation, overall diffusivity increased in both the perpendicular and parallel directions, but the perpendicular direction increased more, indicating demyelination.
  • There was a radiation dose-dependent response in both overall diffusivity (+ 4.4 x 10 -6 mm 2 s -1 /Gy and FA (-0.034/Gy).
  • There was a significant correleation between dose and FA during radiation (from 3 weeks to 19 weeks), but at 32 weeks, this was no longer significant.
  • Parallel diffusion changes (indicating axonal damage) were not significant early on, but became significant at 32 weeks. This indicates that axon damage is a late radiation change.

Author's Conclusions

  • Diffusion tensor MR imaging of corpus callosum genu can measure white matter demyelination and axonal damage in patients undergoing brain radiotherapy.
  • There were dose-dependent acute and subacute decreases in NAWM myelination from brain irradiation.
  • Axonal injury occurs later and is also dose-dependent.

Clinical/Scientific Implications

  • The early and late sequelae of brain radiotherapy are poorly understood. The technique described by the authors using diffusion tensor MR imaging of white matter provides a tool to study these changes.
  • The relationship between demyelination / axonal damage and clinically important side-effects, such as somnolence syndrome, neurocognitive deficits, and brain necrosis, are still unknown. Such imaging techniques may be used for predication of these late effects.


Smoothies for All Occasions
by OncoLink Editorial Team
May 24, 2016