Agarwal Shubhangi, Decavel-Bueff Emilie, Wang Yung-Hua, Qin Hecong, Santos Romelyn Delos, Evans Michael J, Sriram Renuka
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, United States.
Front Oncol. 2022 Jun 23;12:851192. doi: 10.3389/fonc.2022.851192. eCollection 2022.
Tuberous sclerosis complex (TSC) is an inherited genetic disorder characterized by mutations in or class of tumor suppressers which impact several organs including the kidney. The renal manifestations are usually in the form of angiomyolipoma (AML, in 80% of the cases) and cystadenomas. mTOR inhibitors such as rapamycin and everolimus have shown efficacy in reducing the renal tumor burden. Early treatment prevents the progression of AML; however, the tumors regrow upon cessation of therapy implying a lifelong need for monitoring and management of this morbid disease. There is a critical need for development of imaging strategies to monitor response to therapy and progression of disease which will also facilitate development of newer targeted therapy. In this study we evaluated the potential of multiparametric H magnetic resonance imaging (mpMRI) to monitor tumor response to therapy in a preclinical model of TSC, the transgenic mouse A/J . We found 2-dimensional T-weighted sequence with 0.5 mm slice thickness to be optimal for detecting renal lesions as small as 0.016 mm. Baseline characterization of lesions with MRI to assess physiological parameters such as cellularity and perfusion is critical for distinguishing between cystic and solid lesions. Everolimus treatment for three weeks maintained tumor growth at 36% from baseline, while control tumors displayed steady growth and were 70% larger than baseline at the end of therapy. Apparent diffusion coefficient, T values and normalized T intensity changes were also indictive of response to treatment. Our results indicate that standardization and implementation of improved MR imaging protocols will significantly enhance the utility of mpMRI in determining the severity and composition of renal lesions for better treatment planning.
结节性硬化症（TSC）是一种遗传性基因疾病，其特征是肿瘤抑制因子的突变，这会影响包括肾脏在内的多个器官。肾脏表现通常为血管平滑肌脂肪瘤（AML，80%的病例）和囊腺瘤。雷帕霉素和依维莫司等mTOR抑制剂已显示出在减轻肾脏肿瘤负担方面的疗效。早期治疗可防止AML进展；然而，治疗停止后肿瘤会复发，这意味着需要对这种疾病进行终身监测和管理。迫切需要开发成像策略来监测治疗反应和疾病进展，这也将促进新型靶向治疗的发展。在本研究中，我们评估了多参数氢磁共振成像（mpMRI）在TSC临床前模型转基因小鼠A/J中监测肿瘤治疗反应的潜力。我们发现，层厚为0.5毫米的二维T加权序列最适合检测小至0.016毫米的肾脏病变。用MRI对病变进行基线特征分析以评估细胞密度和灌注等生理参数，对于区分囊性和实性病变至关重要。依维莫司治疗三周后，肿瘤生长维持在较基线水平高36%，而对照肿瘤则持续生长，在治疗结束时比基线水平大70%。表观扩散系数、T值和归一化T强度变化也表明了对治疗的反应。我们的结果表明，改进的磁共振成像方案的标准化和实施将显著提高mpMRI在确定肾脏病变的严重程度和组成以进行更好的治疗规划方面的效用。
