2546 - The Comprehensive Assessment of Early-Stage Radiation Induced Cardiac Toxicity Using Hyperpolarized 13 C-MRI and In Vivo DNP MRI
Presenter(s)
M. Matsuo1,2, S. Azuma2, H. Imai1,2, A. E. Elhelaly2, M. Ito2, Y. Takai2, N. Banura2, H. Tomita3, T. Mori4, and F. Hyodo5; 1Innovation Research Center for Quantum Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan, 2Gifu University School of Medicine, Department of Radiology, Gifu, Japan, 3Gifu University, Department of Tumor Pathology, Gifu, Japan, 4Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan, 5Department of Pharmacology, Graduate School of Medicine, Gifu University, Gifu, Japan
Purpose/Objective(s): Radiation therapy is essential for thoracic malignancies, however, cardiac exposure carries a risk of radiation-induced heart disease (RIHD) in the late stages. Recently, Hyperpolarized 13C-MRI and in vivo dynamic nuclear polarization (DNP) MRI have emerged as established techniques to enhance NMR signals, enabling metabolic and redox imaging to assess adverse events of radiation therapy. This study aimed to monitor early metabolic and redox changes in the heart following radiation therapy using these techniques in a murine model.
Materials/Methods: All animal care and experimental procedures were approved by the Gifu University Animal Experiment Committee. C57BL/6 mice (n=4-5 per group) received single-dose whole-chest irradiation (10 or 25 Gy) using a 6 MV linear accelerator. Hyperpolarization 13C-MRI and in vivo DNP MRI were performed at baseline (pre-irradiation) and at 3 and 7 days post-irradiation. On day 8, ex vivo hyperpolarized 13C-MRI and histopathological examinations were conducted. Data were analyzed using Student’s t-test (p < 0.05).
Results: Hyperpolarized 13C-MRI revealed a significant increase in lactate/pyruvate ratios on day 3 post-irradiation compared to pre-irradiation in both the 10 and 25 Gy groups (p < 0.05), with a slight decrease on day 7 relative to day 3. In contrast, ex vivo examination showed a significant decrease (p < 0.05) in this ratio compared to the control on day 8 post-irradiation (control: 0.253, 10 Gy: 0.081, 25 Gy: 0.095). Redox imaging via in vivo DNP MRI showed a conspicuous reduction in free radical probes, the 10 Gy group exhibited faster signal decay on day 3, while the 25 Gy group showed marked, gradual decay on both days 3 and 7. Histopathology revealed the hyperplasia of fibrosis and hyperplasia of capillaries, though atrophy and necrosis remained minimal, suggesting that metabolic and redox changes precede late-stage myocardial damage.
Conclusion: Metabolic and redox imaging are valuable tools for assessing early-stage radiation-induced cardiac toxicity. These 13C-MRI and in vivo DNP MRI techniques offer the potential for non-invasive, early diagnosis of RIHD, potentially leading to improved prevention and management strategies.