动脉自旋标记灌注成像对软组织VX2肿瘤血管生成的评价
Evaluation of angiogenesis of VX2 soft tissue tumor by arterial spin labeling perfusion imaging
摘要目的 评价有关兔软组织VX2肿瘤血管生成的2个病理学指标,即微血管密度(MVD)和血管内皮生长因子(VEGF)表达水平与MR动脉自旋标记(ASL)灌注成像所测血流量(BF)值的相关性.方法 将VX2肿瘤接种于18只新西兰兔右侧后腿肌肉内,3~4周后对实验兔行ASL灌注成像检查.所得图像被传输到一台独立的计算机进行处理,生成BF参数图,测量在肿瘤内所选2~4个ROI的BF值.随后处死实验用兔,获取肿瘤标本,在与ASL灌注图像上的ROI相对应的非坏死部分进行取材,对所获肿瘤组织行CD31和VEGF免疫组织化学染色,然后测量其MVD和VEGF表达水平.采用Spearman相关分析法评价VX2肿瘤组织的MVD和VEGF表达水平与BF值的相关性.结果 BF参数图显示存活肿瘤组织与肌肉相比呈明显的高BF值,部分肿瘤内可见血流灌注缺失区.显微镜下,CD31抗体标记染色的微小血管呈棕黄色染色区域;VEGF染色阳性者则表现为胞质内出现棕红色的区域.共分析了39块VX2肿瘤组织,其BF(M值为6.4 ml·100 g-1·min-1)与肿瘤的MVD(M值为6.8条/个视野)呈显著正相关(r=0.906,P<0.01),与VEGF表达水平(M值为8%)无明显相关(r=0.116,P=0.483).结论 BF值通过反映肿瘤的MVD可用于评价肿瘤的血管生成情况,从而帮助判断其预后并指导治疗.
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abstractsObjective To evaluate the relationship between the blood flow values generated from MR arterial spin labeling (ASL) perfusion imaging and pathologic indicators of angiogenesis including microvascular density (MVD) counts and vascular endothelial growth factor (VEGF) expression levels of VX2 carcinoma in rabbit soft tissue. Methods VX2 tumor was inoculated in the muscular tissue of right posterior limbs of 18 healthy New Zealand white rabbits ,on which arterial spin labeling perfusion imaging was performed by using flow sensitive alternating inversion recovery pulse sequence 3 to 4 weeks later. Arterial spin labeling images were transferred to an independent computer for post-processing and blood flow (BF) maps were generated from them. BF values were measured in 2-4 regions of interest (ROIs) for each tumor. The rabbits were sacrificed after MR imaging. The gross specimens of tumors were obtained and tumor tissues were taken from the non-necrotic regions corresponding to ROIs on BF maps. Immunohistochemical staining of the specimens was performed by using CD31 monoclonal antibody to calculate MVD counts, using VEGF antibody to calculate VEGF expression levels. Correlation between BF values and MVD counts as well as between BF values and VEGF expression levels was evaluated using Spearman correlative analysis.Results On BF maps, viable tumor tissues showed high BF values compared with muscle, but there were areas without blood perfusion in some tumors. Under microscope, the microvessels positively stained by CD31 appeared as light brown areas, and the cells positively staied by VEGF showed reddish brown areas within their cytoplasm. Totally 39 pieces of VX2 tumor tissue were analyzeed There was a significant positive correlation between the BF values(M =6. 4 ml · 100 g-1 · min-1 ) and MVD counts(M =6. 8) (r = 0. 906,P < 0. 01 ), and no significant correlation between BF values and VEGF expression levels ( M = 8% ) ( r =0. 116, P=0.483). Conclusion BF value can be used in evaluating angiogenesis of soft tissue tumor through its reflection of MVD counts, and thus may be helpful in evaluating the prognosis of soft tissue tumor and making plan for their treatment.
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