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基于MRI与病理对照的骨肉瘤动态增强MRI定量参数与肿瘤微循环及乏氧性表达的相关性研究
引用本文:李佳璐,王瑶,马焕,李梅,李鹍,丁莹莹,陶海波.基于MRI与病理对照的骨肉瘤动态增强MRI定量参数与肿瘤微循环及乏氧性表达的相关性研究[J].中国肿瘤临床,2021,48(18):940-945.
作者姓名:李佳璐  王瑶  马焕  李梅  李鹍  丁莹莹  陶海波
作者单位:1.杭州医学院附属临安人民医院放射科 (杭州市310000)
摘    要:  目的  基于MRI与病理对照,探讨动态增强MRI(dynamic contrast-enhanced MRI,DCE-MRI)定量参数与骨肉瘤微循环和乏氧性表达的相关性。  方法  分析云南省肿瘤医院2019年1月至2020年6月收治的原发于膝关节周围的骨肉瘤患者,手术前行MRI检查。术后取瘤段正中矢状面组织切片,并分割为1 cm×1 cm组织块。检测每个组织块肿瘤坏死率(tumor necrosis rate,TNR)、微血管密度(microvessel density,MVD)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、乏氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α),并按照Huvos分级标准划分为反应良好组(TNR≥90%)和反应差组(TNR<90%)。在对应位置的DCE-MRI图像上,定位划分与病理样本等感兴趣区,并测量定量参数(Ktrans、Kep、Ve、Vp)。探讨各定量参数与MVD、VEGF、HIF-1α的关系并绘制ROC曲线。  结果  入组10例骨肉瘤患者,共取得460个肿瘤病理组织块,其中反应良好组59个(12.8%),反应差组401个(87.2%);VEGF阳性311个(67.6%),阴性149个(32.4%);HIF-1α阳性68个(14.8%),阴性392个(85.2%)。反应良好组Ktrans、Kep、Ve、Vp、MVD计数、VEGF阳性率均高于反应差组,而HIF-1α阳性率低于反应差组(P<0.05)。Ktrans、Kep、Ve与MVD具有相关性,回归系数分别为-0.652、0.525、0.418(P<0.01)。Ve预测VEGF、Kep预测HIF-1α阳性表达的阈值、曲线下面积、敏感性、特异性分别为0.634、0.609、63.7%、60.0%和0.115/min、0.614、42.2%、83.3%。  结论  DCE-MRI定量参数对骨肉瘤化疗后肿瘤微循环及乏氧性具有一定的评估价值,或可为新辅助化疗疗效评估提供依据。 

关 键 词:骨肉瘤    新辅助化疗    动态增强磁共振成像    肿瘤微环境    乏氧
收稿时间:2021-06-21

Correlation between quantitative parameters of dynamic contrast-enhanced MRI and microcirculation and hypoxia in osteosarcoma based on the comparison of MRI and histopathological findings
Affiliation:1.Department of Radiology, Hangzhou Medical College Affiliated Lin'an People's Hospital, Hangzhou 310000, China2.Department of Radiology, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Kunming 650018, China3.Department of Pathology, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Kunming 650018, China
Abstract:  Objective  To investigate the correlation between the quantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) and microcirculation and hypoxia in osteosarcoma based on the comparison of MR and histopathological findings.  Methods  Patients with osteosarcoma originating around the knee joint, who underwent MRI after neoadjuvant chemotherapy, were enrolled in Yunnan Cancer Hospital from January 2019 to June 2020. After surgery, a tissue slice was taken from the median sagittal plane of the gross specimen and divided into several 1 cm × 1 cm tissue blocks. The tumor necrosis rate (TNR), microvessel density (MVD), vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α) of each tissue block were detected. According to the Huvos grading standard, specimens were classified into the good response group (TNR ≥ 90%) and poor response group (TNR<90%). On the sagittal DCE-MRI images, the regions of interest corresponding to the tissue blocks were located and quantitative parameters (Ktrans, Kep, Ve, and Vp) were measured. The relationship between the quantitative parameters and MVD, VEGF, and HIF-1 α was explored, and the receiver operating characteristic curve (ROC) was plotted.  Results  A total of 460 histopathological specimens were obtained from10 patients with osteosarcoma, including 59 (12.8%) in the good response group and 401 (87.2%) in the poor response group; 311 (67.6%) were VEGF-positive and 149 (32.4%) were VEGF-negative; 68 (14.8%) were HIF-1α-positive and 392 (85.2%) were HIF-1α-negative. Ktrans, Kep, Ve, Vp, MVD, and the positive rate of VEGF in the good response group were higher than those in the poor response group, while the positive rate of HIF-1α was lower than that in the poor response group (P<0.05). Ktrans, Kep, and Ve were correlated with MVD, and the regression coefficients were -0.652, 0.525, and 0.418, respectively (P<0.01). The threshold, area under the curve, sensitivity, and specificity of Ve for VEGF and those of Kep for HIF-1α were respectively 0.634, 0.609, 63.7%, and 60.0% and 0.115/min, 0.614, 42.2%, and 83.3%.  Conclusions  The quantitative parameters of DCE-MRI can be used to evaluate the microvessel status and hypoxia condition in the histopathological tissues of osteosarcoma, which could be a method of evaluating the efficacy of neoadjuvant chemotherapy. 
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