A novel murine model for localized radiation necrosis and its characterization using advanced magnetic resonance imaging.
OBJECTIVE
To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques.


METHODS
Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis.


RESULTS
Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 microm(2)/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 microm(2)/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis.


CONCLUSIONS
This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.
Jost
Sarah C
SC
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hope
Andrew
A
Kiehl
Erich
E
Perry
Arie
A
Travers
Sarah
S
Garbow
Joel R
JR
D000818:Animals; D001921:Brain / Q000473:pathology* / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D016371:Cranial Irradiation / Q000379:methods; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000209:etiology / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D020266:Radiotherapy, Conformal; D013997:Time Factors