Purpose: Differentiation between radiation-induced necrosis and tumor recurrence is crucial to determine proper management strategies but continues to be one of the central challenges in neuro-oncology. We hypothesized that hyperpolarized 13C MRI, a unique technique to measure real-time in vivo metabolism, would distinguish radiation necrosis from tumor on the basis of cell-intrinsic metabolic differences. The purpose of this study was to explore the feasibility of using hyperpolarized [1-13C]pyruvate for differentiating radiation necrosis from brain tumors.
Procedures: Radiation necrosis was initiated by employing a CT-guided 80-Gy single-dose irradiation of a half cerebrum in mice (n = 7). Intracerebral tumor was modeled with two orthotopic mouse models: GL261 glioma (n = 6) and Lewis lung carcinoma (LLC) metastasis (n = 7). 13C 3D MR spectroscopic imaging data were acquired following hyperpolarized [1-13C]pyruvate injection approximately 89 and 14 days after treatment for irradiated and tumor-bearing mice, respectively. The ratio of lactate to pyruvate (Lac/Pyr), normalized lactate, and pyruvate in contrast-enhancing lesion was compared between the radiation-induced necrosis and brain tumors. Histopathological analysis was performed from resected brains.
Results: Conventional MRI exhibited typical radiographic features of radiation necrosis and brain tumor with large areas of contrast enhancement and T2 hyperintensity in all animals. Normalized lactate in radiation necrosis (0.10) was significantly lower than that in glioma (0.26, P = .004) and LLC metastatic tissue (0.25, P = .00007). Similarly, Lac/Pyr in radiation necrosis (0.18) was significantly lower than that in glioma (0.55, P = .00008) and LLC metastasis (0.46, P = .000008). These results were consistent with histological findings where tumor-bearing brains were highly cellular, while irradiated brains exhibited pathological markers consistent with reparative changes from radiation necrosis.
Conclusion: Hyperpolarized 13C MR metabolic imaging of pyruvate is a noninvasive imaging method that differentiates between radiation necrosis and brain tumors, providing a groundwork for further clinical investigation and translation for the improved management of patients with brain tumors.
Keywords: Brain tumor; Hyperpolarized carbon-13; Magnetic resonance imaging; Radiation necrosis.