Angiogenesis: Noninvasive quantitative assessment with contrast- enhanced functional US in murine model
Angiogenesis: Noninvasive quantitative assessment with contrast- enhanced functional US in murine model
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DOI：
10.1148/radiol.2392040986
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发表时间：
2006-06-01
期刊：
影响因子：
19.7
通讯作者：
Mattrey, Robert F.
中科院分区：
文献类型：
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作者：
Lucidarme, Olivier;Kono, Yuko;Mattrey, Robert F.
目的：利用微泡破坏动力学评价定量功能超声(US)在小鼠凝胶模型中的应用，以确定US提供的参数指标是否有助于评估血管生成。材料和方法：机构动物学科委员会批准的实验和方法。在36只正常小鼠的脊柱两侧皮下放置两个0.4毫升的凝胶植入物。一种植入物每毫升凝胶含有0.5、1.0或1.5微克的人碱性成纤维细胞生长因子(BFGF)。于术后第3、6、9、12天用微泡造影剂对血管生成进行功能超声定量分析，收集组织学资料。用数学衰减模型拟合种植体的时间-强度曲线，计算出每单位时间的血容量分数和血液置换分数。抗CD31染色后测量微血管密度(MVD)和微血管面积百分比(MVA)。结果：在第3、6、9和12天，含碱性成纤维细胞生长因子的种植体诱导的MVD分别为8、35、42和42条/平方毫米，而对照组的MVD为4条/mm(2)(P<；0.05)。含碱性成纤维细胞生长因子的种植体诱导MVA的百分比分别为2%、5%、20%和27%，而对照组为0.5%(P<；0.05)。与对照组(11.0+/-5.5，P<；.001)相比，碱性成纤维细胞生长因子种植体的最大增强强度(23.3灰度级+/-14.1[标准差])显著增加。在超声下，含有bFGF的植入物的血容量分数与MVD(r(2)=0.42)或MVA百分比(r(2)=0.51)之间的相关性很差。微泡速度与MVD(r(2)=0.05)或MVA百分比(r(2)<；0.13)无相关性。结论：功能性超声灌注参数与目前用于定量血管生成的组织学指标无关。微血管密度作为血管生成的组织学定量测量，可能不是依赖于灌注的新生血管的对比增强成像的合适标准。
Purpose: To evaluate quantitative functional ultrasonography ( US) in a murine gel model by using microbubble destruction kinetics to determine whether parametric indices provided with US could help assess angiogenesis.Materials and Methods: Institutional Animal Subjects Committee approved experiments and procedures. In 36 normal mice, two 0.4-mL gel implants were placed subcutaneously on either side of spine. One implant contained 0.5, 1.0, or 1.5 mu g human basic fibroblast growth factor (bFGF) per milliliter of gel. Functional US quantitative analysis of angiogenesis with microbubble contrast agent was performed on days 3, 6, 9, and 12; histologic data were collected. Time-intensity curve of implant was fitted to mathematic decay model to calculate fractional blood volume and fraction of blood replaced per unit of time. Microvascular density (MVD) and percentage of microvascular area (MVA) were measured after anti-CD31 staining. Spearman rank order correlation was used in analyses.Results: bFGF-containing implants induced MVD of eight, 35, 42, and 42 vessels per square millimeter on days 3, 6, 9, and 12, respectively; in controls, MVD was four vessels/mm(2) (P < .05 on days 6, 9, and 12). bFGF-containing implants induced percentage MVA of 2%, 5%, 20%, and 27%, respectively; in controls, it was 0.5% (P < .05). Maximum enhancement was significantly increased in bFGF implants (23.3 gray level +/- 14.1 [standard deviation]) compared with controls (11.0 +/- 5.5, P < .001). Implants containing bFGF showed poor correlations between fractional blood volume and MVD (r(2) = 0.42) or percentage MVA (r(2) = 0.51) at US. There was no correlation between microbubble velocity and MVD (r(2) = 0.05) or percentage MVA (r(2) < 0.13).Conclusion: Functional US perfusion parameters do not correlate with current histologic indices for quantifying angiogenesis. MVD, as a histologic quantitative measurement of angiogenesis, may not be an appropriate standard for contrast-enhanced imaging that relies on perfused neovessels.