Regional differences in radiosensitivity across the rat cervical spinal cord

Abstract

Purpose: To study regional differences in radiosensitivity within the rat cervical spinal cord.

Methods and materials: Three types of inhomogeneous dose distributions were applied to compare the radiosensitivity of the lateral and central parts of the rat cervical spinal cord. The left lateral half of the spinal cord was irradiated with two grazing proton beams, each with a different penumbra (20-80% isodoses): lateral wide (penumbra = 1.1 mm) and lateral tight (penumbra = 0.8 mm). In the third experiment, the midline of the cord was irradiated with a narrow proton beam with a penumbra of 0.8 mm. The irradiated spinal cord length (C1-T2) was 20 mm in all experiments. The animals were irradiated with variable single doses of unmodulated protons (150 MeV) with the shoot-through method, whereby the plateau of the depth-dose profile is used rather than the Bragg peak. The endpoint for estimating isoeffective dose (ED(50)) values was paralysis of fore and/or hind limbs within 210 days after irradiation. Histology of the spinal cords was performed to assess the radiation-induced tissue damage.

Results: High-precision proton irradiation of the lateral or the central part of the spinal cord resulted in a shift of dose-response curves to higher dose values compared with the homogeneously irradiated cervical cord to the same 20-mm length. The ED(50) values were 28.9 Gy and 33.4 Gy for the lateral wide and lateral tight irradiations, respectively, and as high as 71.9 Gy for the central beam experiment, compared with 20.4 Gy for the homogeneously irradiated 20-mm length of cervical cord. Histologic analysis of the spinal cords showed that the paralysis was due to white matter necrosis. The radiosensitivity was inhomogeneously distributed across the spinal cord, with a much more radioresistant central white matter (ED(50) = 71.9 Gy) compared with lateral white matter (ED(50) values = 28.9 Gy and 33.4 Gy). The gray matter did not show any noticeable lesions, such as necrosis or hemorrhage, up to 80 Gy. All lesions induced were restricted to white matter structures.

Conclusions: The observed large regional differences in radiosensitivity within the rat cervical spinal cord indicate that the lateral white matter is more radiosensitive than the central part of the white matter. The gray matter is highly resistant to radiation: no lesions observable by light microscopy were induced, even after a single dose as high as 80 Gy.