Distinguishing tumor recurrence from radiation necrosis following brain tumor therapy remains a major clinical challenge. Here we demonstrate the ability to distinguish these lesions using the amide proton transfer (APT) MRI signals of endogenous cellular proteins and peptides as an imaging biomarker. When comparing two orthotopic glioma models (SF188/V+ glioma and 9L gliosarcoma) with a radiation necrosis model in rats, viable glioma (hyperintense) and radiation necrosis (hypointense to isointense) could be clearly differentiated using APT MRI. When irradiating rats with U87MG gliomas, the APT signals in the irradiated tumors decreased significantly at 3 days and 6 days post-radiation. The amide protons detected by APT provide a unique and non-invasive MRI biomarker for assessing viable malignancy versus radiation necrosis and predicting tumor response to therapy.

Amide proton transfer (APT) imaging is a novel MRI technique, in which the amide protons of endogenous proteins and peptides are irradiated to accomplish indirect detection using the bulk water signal. In this paper, the APT approach was added to a standard brain MRI protocol at 3T, and twelve patients with high-grade gliomas confirmed by histopathology were scanned. It is shown that all tumors, including one with minor gadolinium enhancement, showed heterogeneous hyperintensity on the APT images. The average APT signal intensities of the viable tumor cores were significantly higher than those of peritumoral edema and normal-appearing white matter (P < 0.001). The average APT signal intensities were significantly lower in the necrotic regions than in the viable tumor cores (P = 0.004). The APT signal intensities of the cystic cavities were similar to those of the viable tumor cores (P > 0.2). The initial results show that APT imaging at the protein and peptide level may enhance non-invasive identification of tissue heterogeneity in high-grade brain tumors.

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (L // ), and radial diffusivity (L ? ) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in L // from 4 to 40 weeks postradiation, and an increase in L ? with return to baseline in L // at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in L // correlated with reactive astrogliosis (P < 0.01) and L ? correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in L // and L ? . DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

Increased lambda(perpendicular) with no significant change in lambda(parallel) appears to characterize noncystic WM injury with reduced myelination, whereas reduction in both lambda(parallel) and lambda(perpendicular) characterize severe damage with loss of structural integrity and necrosis. Combining with FA and trace, lambda(parallel) and lambda(perpendicular) provide additional information which reflects type and severity of HI injury.