Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models
Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models
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DOI：
10.1158/0008-5472.can-05-0440
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发表时间：
2005-06-15
期刊：
影响因子：
11.2
通讯作者：
Chambers, AF
中科院分区：
文献类型：
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作者：
Graham, KC;Wirtzfeld, LA;Chambers, AF
肝转移是与黑色素瘤、结肠癌和乳腺癌相关的死亡率的临床重要因素。临床前小鼠模型对肝转移的研究至关重要，但由于无法以无创和纵向的方式研究这一动态过程，它们的效用受到限制。本研究表明，三维高频超声可以无创地跟踪肝转移瘤的生长，并在实验性肝转移模型中评估潜在的化疗药物。通过肠系膜静脉注射B16F1（小鼠黑色素瘤）、PAP2（小鼠h -ras转化成纤维细胞）、HT-29（人结肠癌）和MDA-MB-435/HAL（人乳腺癌）细胞产生的肝转移进行了鉴定和纵向追踪。肿瘤的大小和位置经组织学检查证实。根据三维体积数据计算肿瘤体积，单个肝转移呈指数增长。通过将三维分割体积与直径测量和椭球形状假设估计的体积进行比较，显示了体积成像对减少肿瘤体积测量不确定性的重要性。高频超声成像在评价治疗干预措施中的效用是通过阿霉素治疗试验建立的。这些结果表明，三维高频超声成像可能特别适合于临床前肝转移模型中转移进展的定量评估和化疗药物的评估。
Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential to the study of liver metastasis' yet their utility has been limited by the inability to study this dynamic process in a noninvasive and longitudinal manner. This study shows that three-dimensional high-frequency ultrasound can be used to noninvasively track the growth of liver metastases and evaluate potential chemotherapeutics in experimental liver metastasis models. Liver metastases produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H-ras-transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL (human breast carcinoma) cells were identified and tracked longitudinally. Tumor size and location were verified by histologic evaluation. Tumor volumes were calculated from the three-dimensional volumetric data, with individual liver metastases showing exponential growth. The importance of volumetric imaging to reduce uncertainty in tumor volume measurement was shown by comparing three-dimensional segmented volumes with volumes estimated from diameter measurements and the assumption of an ellipsoid shape. The utility of high-frequency ultrasound imaging in the evaluation of therapeutic interventions was established with a doxorubicin treatment trial. These results show that three-dimensional high-frequency ultrasound imaging may be particularly well suited for the quantitative assessment of metastatic progression and the evaluation of chemotherapeutics in preclinical liver metastasis models.