Muñoz Nina M, Minhaj Adeeb A, Maldonado Kiersten L, Kingsley Charles V, Cortes Andrea C, Taghavi Houra, Polak Urszula, Mitchell Jennifer M, Ensor Joe E, Bankson James A, Rashid Asif, Avritscher Rony
Department of Interventional Radiology at The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.
Department of Imaging Physics at The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.
Magn Reson Imaging. 2019 Apr;57:156-164. doi: 10.1016/j.mri.2018.11.012. Epub 2018 Nov 19.
To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC).
Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively.
Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (K) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min, p < 0.01), indicating a substantial decrease in vascular permeability caused by the therapy. This reduction was associated with decreased MVD (3.9 vs 10.8% CD34+ cells, p < 0.01), higher tumor necrosis (31.9 vs 21.8%, p < 0.001) and hypoxia (19.7 vs 10.5% pimonidazole binding, p < 0.01). Moreover, statistical analysis demonstrate significant correlation of DCE-MRI K with histopathologic tissue necrosis (r = -0.537, p < 0.05) and MVD (r = 0.599, p < 0.05). Interestingly, none of the CEUS measurements were significantly different between the control and treatment groups, and did not show statistical correlation with any of the histopathological parameters assessed (p > 0.05).
Sorafenib-induced reduction in vascular permeability in this preclinical model of HCC is detected more accurately through DCE-MRI than CEUS, and DCE-MRI parameters strongly correlate with histopathological changes in tissue vascularization and tissue necrosis.
在肝细胞癌（HCC）大鼠模型中，比较超声造影（CEUS）和动态对比增强（DCE）磁共振成像（MRI）评估索拉非尼治疗后组织血管生成变化的准确性。
雄性布法罗大鼠原位肝肿瘤模型，通过口服灌胃每日给予7.5mg/kg索拉非尼，持续2周（n = 9）。在肿瘤植入后2周（即治疗开始前）以及治疗结束后（即肿瘤收获前）对其进行DCE-MRI和CEUS检查。未治疗的动物（n = 10）作为对照。肿瘤组织切片进行苏木精-伊红、匹莫硝唑和CD34染色，分别用于定量评估坏死、缺氧和微血管密度（MVD）。
在所有评估的DCE-MRI参数中，只有容积转运常数（K）测量值在索拉非尼治疗的肿瘤中显著降低（0.18对0.33min，p < 0.01），表明该治疗导致血管通透性大幅下降。这种降低与MVD降低（3.9对10.8% CD34+细胞，p < 0.01）、更高的肿瘤坏死（31.9对21.8%，p < 0.001）和缺氧（19.7对10.5%匹莫硝唑结合，p < 0.01）相关。此外，统计分析表明DCE-MRI的K与组织病理学组织坏死（r = -0.537，p < 0.05）和MVD（r = 0.599，p < 0.05）有显著相关性。有趣的是，CEUS测量值在对照组和治疗组之间没有显著差异，并且与所评估的任何组织病理学参数均无统计学相关性（p > 0.05）。
在该HCC临床前模型中，通过DCE-MRI比CEUS更准确地检测到索拉非尼诱导的血管通透性降低，并且DCE-MRI参数与组织血管生成和组织坏死的组织病理学变化密切相关。
