Evaluation of tumor angiogenesis by dynamic MRI and compartment analysis

血管生成与肿瘤的生长、侵袭和转移密切相关。尽管肿瘤血流量通过血管生成而增加，但目前还没有建立无创测量体内肿瘤血流量的方法。在本研究项目中，我们开发了一种利用动态GdDTPA增强磁共振成像(MRI)和隔室分析来定量测量体内肿瘤血流量(TBF)的新方法。通过基础体模研究，我们证实了MRI信号强度与Gd-DTPA浓度之间良好的线性关系。我们初步测量了志愿者的正常肌肉血流量，证实了团注Gd-DTPA后，用动脉输入函数进行去卷积分析和房室分析，可以很好地测量肌肉血流量。我们将我们的方法应用于骨和软组织肿瘤患者，成功地生成了具有高时间(扫描时间=3.2秒)和空间分辨率(逐个像素)的TBF功能图。TBF图清楚地显示了TBF的异质性，即肿瘤周围因血管生成而导致的TBF增加，而肿瘤中心的TBF较低。全血流图显示化疗后全血流量显著降低。因此，TBF MAP是一种很有前途的评估肿瘤血流的工具，并可能有助于评估治疗反应。有必要评估我们的方法是否适用于其他区域的肿瘤，因为到目前为止，这些区域的动态数据分析会受到运动伪影的阻碍。在未来的研究中，也有必要将TBF图与其他成像方式和组织病理学发现的结果进行比较。

Angiogenesis correlates with tumor growth, invasion and metastasis. Although tumor blood flow increased by angiogensis, it has not been established to noninvasively measure tumor blood flow in vivo. In this research project, we have developed a new method for quantitative measurement of tumor blood flow (TBF) in vivo by using dynamic GdDTPA enhanced magnetic resonance imaging (MRI) and compartment analysis. By fundamental phantom studies, we confirmed good linear relationships between MRI signal intensities and Gd-DTPA concentrations. Preliminarily, we measured normal muscle blood flow in volunteers and confirmed that muscle blood flow could be measured with a good reproducibily by deconvolution analysis and compartment analysis using arterial input function after a bolus injection of Gd-DTPA. We applied our methods in patients with bone and soft-tissue tumors and successfully generated a functional map of TBF with high temporal (scan time = 3.2 sec) and spatial resolution (pixel-by-pixel). TBF map clearly demonstrated heterogeneity of TBF, i.e. increased TBF in tumor periphery due to angiogenesis and low TBF in center of tumor. TBF map showed substantially decreased TBF after chemotherapy. Thus, TBF map would be a promising tool for evaluating tumor blood flow and may be useful to evaluate treatment response. It is necessary to evaluate if our methods could be applied to tumor of other regions where dynamic data analysis would be hindered by motion artifact to date. In future studies, it is also warranted to compare the TBF maps with the results of other imaging modalities and histopathologic findings.