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.

中文翻译：

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使用超极化碳 13 MR 代谢成像区分放射性坏死与脑肿瘤

目的

区分辐射引起的坏死和肿瘤复发对于确定适当的管理策略至关重要，但仍然是神经肿瘤学的核心挑战之一。我们假设超极化¹³ C MRI 是一种独特的实时测量体内代谢的技术，可以根据细胞内在代谢差异区分放射性坏死和肿瘤。本研究的目的是探索使用超极化[1- ¹³ C]丙酮酸区分放射性坏死和脑肿瘤的可行性。

程序

通过对小鼠的半个大脑进行 CT 引导的 80-Gy 单剂量照射（n  = 7），引发了放射性坏死。使用两种原位小鼠模型对脑内肿瘤进行建模：GL261 神经胶质瘤 ( n  = 6) 和 Lewis 肺癌 (LLC) 转移瘤 ( n  = 7)。¹³ C 3D MR 光谱成像数据在超极化[1- ¹³ C]丙酮酸注射后分别在辐照小鼠和荷瘤小鼠治疗后约89天和14天获得。比较了辐射诱导的坏死和脑肿瘤之间的对比增强病灶中乳酸与丙酮酸的比率 (Lac/Pyr)、标准化乳酸和丙酮酸。从切除的大脑中进行组织病理学分析。

结果

常规 MRI 表现出典型的放射性坏死和脑肿瘤的放射学特征，在所有动物中都有大面积的对比增强和 T2 高信号。放射性坏死 (0.10) 中的标准化乳酸显着低于胶质瘤 (0.26, P =  .004) 和 LLC 转移组织 (0.25, P =  .00007)。同样，放射性坏死 (0.18) 中的 Lac/Pyr 显着低于胶质瘤 (0.55, P =  .00008) 和 LLC 转移 (0.46, P =  .000008)。这些结果与组织学发现一致，其中荷瘤大脑是高度细胞的，而受辐射的大脑表现出与放射性坏死的修复性变化一致的病理标志物。

结论

丙酮酸的超极化¹³ C MR 代谢成像是一种无创成像方法，可区分放射性坏死和脑肿瘤，为进一步的临床研究和转化以改善脑肿瘤患者的管理奠定基础。