TY - JOUR
T1 - A Novel Murine Model for Localized Radiation Necrosis and its Characterization Using Advanced Magnetic Resonance Imaging
AU - Jost, Sarah C.
AU - Hope, Andrew
AU - Kiehl, Erich
AU - Perry, Arie
AU - Travers, Sarah
AU - Garbow, Joel R.
N1 - Funding Information:
Supported by a National Institutes of Health (NIH)/National Cancer Institute (NCI) Small Animal Imaging Resource Program grant (U24 CA83060), an NIH grant supporting development of micro-radiotherapy (R21 CA108677), the Alvin J. Siteman Cancer Center at Washington University in St. Louis, an NCI Comprehensive Cancer Center grant (P30 CA91842), and the Saint Louis Brain Tumor Foundation.
PY - 2009/10/1
Y1 - 2009/10/1
N2 - Purpose: 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 and Materials: 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 μm2/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 μm2/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.
AB - Purpose: 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 and Materials: 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 μm2/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 μm2/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.
KW - Animal models
KW - Brain tumor
KW - Conformal radiation
KW - Magnetic resonance imaging
KW - Radiation necrosis
UR - http://www.scopus.com/inward/record.url?scp=69549090039&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2009.06.007
DO - 10.1016/j.ijrobp.2009.06.007
M3 - Article
C2 - 19735877
AN - SCOPUS:69549090039
SN - 0360-3016
VL - 75
SP - 527
EP - 533
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -