Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

Abstract

Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T(1), T(2), apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 × 10 mm(2)) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at ~25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T(1), T(2), MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T(1), T(2), MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.