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Differentiating Radiation Necrosis from Brain Tumor Using Hyperpolarized Carbon-13 MR Metabolic Imaging

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Abstract

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.

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Acknowledgments

The authors would like to thank Chung-Man Moon, Biruk Tesfaye Birhanu, and Nguyen Trong Nguyen for the assistance with the experimental procedure.

Funding

This study was supported by the Ministry of Science and ICT, Republic of Korea (2017R1C1B5018396), the Ministry of Education, Republic of Korea (2019R1I1A3A01059201), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HR20C0021), American Brain Tumor Association (DG1700010), and the DongKook Life Science. Co., Ltd., Republic of Korea.

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Author notes

  1. Ilwoo Park and Seulkee Kim contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Chonnam National University, 42 Jaebongro, Donggu, Gwangju, 61469, South Korea

    Ilwoo Park, Seulkee Kim, Yun Hyeon Kim & Woong Yoon

  2. Department of Radiology, Chonnam National University Hospital, 42 Jaebongro, Donggu, Gwangju, 61469, South Korea

    Ilwoo Park, Yun Hyeon Kim & Woong Yoon

  3. Department of Artificial Intelligence Convergence, Chonnam National University, 77 Yongbong-ro, Bukgu, Gwangju, 61186, South Korea

    Ilwoo Park

  4. Department of Radiology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-gun, Jeollanam-do, Hwasun, 58128, South Korea

    Seulkee Kim

  5. Department of Radiation Oncology, University of California San Francisco, 505 Parnassus Ave, San Francisco, California, 94143, USA

    Daniela Pucciarelli & Jean L. Nakamura

  6. Department of Anatomy, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-gun, Jeollanam-do, Hwasun, 58128, South Korea

    Juhyun Song

  7. Neurosurgery, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-gun, Jeollanam-do, Hwasun, 58128, South Korea

    Jin Myung Choi & Shin Jung

  8. Department of Pathology, Chonnam National University Medical School, 42 Jaebongro, Donggu, Gwangju, 61469, South Korea

    Kyung-Hwa Lee

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  1. Ilwoo Park
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Correspondence to Ilwoo Park.

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Park, I., Kim, S., Pucciarelli, D. et al. Differentiating Radiation Necrosis from Brain Tumor Using Hyperpolarized Carbon-13 MR Metabolic Imaging. Mol Imaging Biol 23, 417–426 (2021). https://doi.org/10.1007/s11307-020-01574-w

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  • DOI: https://doi.org/10.1007/s11307-020-01574-w

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