Wang Yuenan, Guan Fada, Ouyang Fukun, Yuan Hongyan, Su Ming, Ding Xuanfeng
Department of Therapeutic Radiology Yale University School of Medicine New Haven Connecticut USA.
Department of Cardiology Peking University Shenzhen Hospital Shenzhen Guangdong Province P.R. China.
Precis Radiat Oncol. 2024 Nov 12;8(4):200-208. doi: 10.1002/pro6.1246. eCollection 2024 Dec.
Radiation-induced heart disease (RIHD) is a serious complication but difficult to assess in patients undergoing thoracic radiotherapy (RT). We aim to analyze RIHD using heart ultrasound and elastic modulus, exploring relationships between functional, anatomical or biomechanical changes of the heart and radiation dose. Twenty BALB/c mice were divided into four groups (control, 10 Gy, 20 Gy and 25 Gy) with a single fraction of image-guided volumetric modulated arc radiotherapy (VMAT) to murine heart on a linear accelerator. Transthoracic echocardiography (TTE) was performed on a small-animal ultrasound imaging system with a handheld microscan transducer. E-wave/A-wave ratio (E/A) and myocardial performance index (MPI) for diastolic performance were noninvasively evaluated weekly, as well as ejection fraction (EF%), fractional shortening (FS%), left ventricle (LV) mass and heart wall thickening for systolic performance. At the end of the fifth week, all mice were sacrificed for elastic modulus measurement on a dynamic mechanical analyzer (DMA) and for histopathological staining. All experiments were conducted in accordance with the local institution's animal research committee guideline. Significant difference was observed in E/A ratio between the control and 25 Gy irradiated groups (1.8±0.5 and 0.7±0.9, respectively; <0.05), indicating reduced diastolic performance and increased stiffness in left ventricle after high-dose heart radiation. Diastolic dysfunction in irradiated groups was also observed with significantly increased MPI. In contrast, posterior wall thickness, aortic peak velocity, heart rate, EF and FS were not significantly different after RT. Heart elasticity was reduced substantially with the increased radiation dose. HE and Masson Trichrome staining confirmed more fibrosis deposition in irradiated hearts. RIHD evaluation with ultrasound imaging noninvasively and biomechanical modulus measurement invasively in the image guided, precision dose-escalated murine heart irradiation is feasible. Increased myocardial stiffness, abnormal diastolic relaxation, more collagen deposition, and reduced tissue elasticity are observed in irradiated heart tissue. This study may facilitate our understanding of RIHD and facilitate improving patients' quality of life in the future.
放射性心脏病（RIHD）是胸部放疗（RT）患者中一种严重的并发症，但难以评估。我们旨在利用心脏超声和弹性模量分析RIHD，探索心脏功能、解剖或生物力学变化与辐射剂量之间的关系。将20只BALB/c小鼠分为四组（对照组、10 Gy组、20 Gy组和25 Gy组），在直线加速器上对小鼠心脏进行单次图像引导容积调强弧形放疗（VMAT）。使用手持式微扫描换能器在小动物超声成像系统上进行经胸超声心动图（TTE）检查。每周无创评估舒张功能的E波/A波比值（E/A）和心肌性能指数（MPI），以及收缩功能的射血分数（EF%）、缩短分数（FS%）、左心室（LV）质量和心脏壁增厚情况。在第五周结束时，处死所有小鼠，在动态力学分析仪（DMA）上进行弹性模量测量，并进行组织病理学染色。所有实验均按照当地机构的动物研究委员会指南进行。在对照组和25 Gy照射组之间观察到E/A比值有显著差异（分别为1.8±0.5和0.7±0.9；<0.05），表明高剂量心脏辐射后左心室舒张功能降低且僵硬度增加。在照射组中也观察到舒张功能障碍，MPI显著增加。相比之下，放疗后后壁厚度、主动脉峰值速度、心率、EF和FS无显著差异。随着辐射剂量增加，心脏弹性显著降低。苏木精-伊红（HE）染色和马松三色染色证实照射心脏中有更多纤维化沉积。在图像引导、精确剂量递增的小鼠心脏照射中，通过超声成像无创评估和通过生物力学模量测量有创评估RIHD是可行的。在照射的心脏组织中观察到心肌僵硬度增加、舒张松弛异常、更多胶原蛋白沉积和组织弹性降低。本研究可能有助于我们理解RIHD，并在未来有助于改善患者的生活质量。
