Brain metastasis is a common characteristic of late-stage lung cancers. High doses of targeted radiotherapy can control tumor growth in the brain but can also result in radiotherapy-induced necrosis. Current methods are limited for distinguishing whether new parenchymal lesions following radiotherapy are recurrent tumors or radiotherapy-induced necrosis, but the clinical management of these two classes of lesions differs significantly. Here, we developed, validated, and evaluated a new MRI technique termed selective size imaging using filters via diffusion times (SSIFT) to differentiate brain tumors from radiotherapy necrosis in the brain. This approach generates a signal filter that leverages diffusion time dependence to establish a cell size–weighted map. Computer simulations in silico, cultured cancer cells in vitro, and animals with brain tumors in vivo were used to comprehensively validate the specificity of SSIFT for detecting typical large cancer cells and the ability to differentiate brain tumors from radiotherapy necrosis. SSIFT was also implemented in patients with metastatic brain cancer and radiotherapy necrosis. SSIFT showed high correlation with mean cell sizes in the relevant range of less than 20 μm. The specificity of SSIFT for brain tumors and reduced contrast in other brain etiologies allowed SSIFT to differentiate brain tumors from peritumoral edema and radiotherapy necrosis. In conclusion, this new, cell size–based MRI method provides a unique contrast to differentiate brain tumors from other pathologies in the brain. Significance: This work introduces and provides preclinical validation of a new diffusion MRI method that exploits intrinsic differences in cell sizes to distinguish brain tumors and radiotherapy necrosis.

中文翻译：

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选择性细胞大小 MRI 可区分脑肿瘤和放射性坏死


脑转移是晚期肺癌的共同特征。高剂量的靶向放疗可以控制脑部肿瘤的生长，但也可能导致放疗引起的坏死。目前的方法仅限于区分放疗后新出现的实质病变是复发性肿瘤还是放疗引起的坏死，但这两类病变的临床治疗存在显着差异。在这里，我们开发、验证和评估了一种新的 MRI 技术，称为使用扩散时间滤波器 (SSIFT) 的选择性尺寸成像，以区分脑肿瘤和脑部放射治疗坏死。这种方法生成一个信号滤波器，利用扩散时间依赖性来建立细胞大小加权图。通过计算机模拟、体外培养癌细胞和体内患有脑肿瘤的动物，全面验证了SSIFT检测典型大癌细胞的特异性以及区分脑肿瘤和放疗坏死的能力。 SSIFT 还应用于转移性脑癌和放射治疗坏死的患者。 SSIFT 在小于 20 μm 的相关范围内与平均细胞尺寸具有高度相关性。 SSIFT 对脑肿瘤的特异性以及其他脑病因的对比度降低使得 SSIFT 能够将脑肿瘤与瘤周水肿和放射治疗坏死区分开来。总之，这种基于细胞大小的新 MRI 方法提供了独特的对比，可以将脑肿瘤与大脑中的其他病变区分开来。意义：这项工作介绍并提供了一种新的扩散 MRI 方法的临床前验证，该方法利用细胞大小的内在差异来区分脑肿瘤和放射治疗坏死。