Fig 1.
Gamma-Knife dose radiation contours superimposed on a CT image of a mouse.
Panels A, B, and C show sagittal, coronal, and transaxial views, respectively. The three contours shown are at 75% (yellow), 50% (green), and 25% (orange) isodose. The red cross-hairs in each panel identify the location of the imaging planes shown in the other two panels.
Fig 2.
MRI can monitor radiation necrosis in irradiated mouse brain.
Representative contrast-enhanced, transaxial T2-weighted spin-echo images of irradiated mice at 1, 4, 8, and 13 weeks following a single 50-Gy (50% isodose) of radiation. Slices are chosen to display the same anatomic region of the brain at all four time points.
Fig 3.
Mean volumes ± SD (n = 15), vs. time post-irradiation for mice irradiated hemispherically with different dose schedules: 60-Gy in 1 fraction (red), 60-Gy in 3 fractions (green), 50-Gy in 1 fraction (black) and 45-Gy in 1 fraction (blue).
Fig 4.
Representative histologic slides showing irradiation damage of each grade.
All mice were irradiated on the left hemisphere, as displayed. Panels A, C, E, and G are shown at 1x; Panels B, D, F, and H are shown at 10x magnification, thereby revealing more detail in the irradiated areas. Panels A and B (Grade 0): The irradiated brain shows no pathological changes. Panels C and D (Grade 1): The earliest histological events were micro-hemorrhage accompanied by increased numbers of telangiectatic vessels (arrows). Panels E and F (Grade 2): Typically larger parenchymal hemorrhages (arrowhead) and tissue loss (arrows) are observed, with approximately one-half to two-thirds of the left hemisphere involved. (Panels G and H (Grade 3): More extensive areas are typically involved, with severe tissue damage, including fibrinoid vascular necrosis (arrowheads) and tissue loss (arrows).
Fig 5.
Pathological features in post-irradiation mouse brain.
A. Micro-hemorrhage and dilated vessels (arrow, 20X); B. Hemorrhage (arrowheads) and fibrinoid vascular necrosis (arrows) (H&E staining, 20X); C. PTAH staining shows fibrinoid vascular necrosis in dark blue (arrows, 20X); D. Trichrome staining demonstrates fibrinoid vascular necrosis (red, arrows) and collagen deposition (light blue, arrow heads)(60X); E. Macrophages surrounding damaged tissues (arrow, 20x); F. Cellular atypia (arrows, 60X); G. Edema (arrows, 20X); H. Neuronal necrosis (arrows, 60X).
Fig 6.
Histologic scores correlate with MR-derived necrotic volumes and post-irradiation time.
A. Correlation between MR-derived necrotic volumes and histological scores. MR-derived volumes, mean ± SD (n = 30, 37, 27, and 53 for Grade 0, 1, 2, and 3, respectively), of radiation necrosis vs. histological score for irradiated mice, independent of specific radiation dose (45–60 Gy) and treatment schedules. B. Correlation between histological scores and time post irradiation. Box-and-whisker plots of the histological scores for mice receiving 50/60-Gy of radiation, at 4, 8, and 13 weeks post irradiation. The 25th-75th percentiles are blocked by the box, the band inside the box is the mean, and the whiskers mark the maximum and minimum values.