The Goldyne Savad Institute for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Neoplasia. 2011 Mar;13(3):244-53. doi: 10.1593/neo.101354.
Recently, we have demonstrated the feasibility of using hemodynamic response imaging (HRI), a functional magnetic resonance imaging (MRI) method combined with hypercapnia and hyperoxia, for monitoring vascular changes during liver pathologies without the need of contrast material. In this study, we evaluated HRI ability to assess changes in liver tumor vasculature during tumor establishment, progression, and antiangiogenic therapy. Colorectal adenocarcinoma cells were injected intrasplenically to model colorectal liver metastasis (CRLM) and the Mdr2 knockout mice were used to model primary hepatic tumors. Hepatic perfusion parameters were evaluated using the HRI protocol and were compared with contrast-enhanced (CE) MRI. The hypovascularity and the increased arterial blood supply in well-defined CRLM were demonstrated by HRI. In CRLM-bearing mice, the entire liver perfusion was attenuated as the HRI maps were significantly reduced by 35%. This study demonstrates that the HRI method showed enhanced sensitivity for small CRLM (1-2 mm) detection compared with CE-MRI (82% versus 38%, respectively). In addition, HRI could demonstrate the vasculature alteration during CRLM progression (arborized vessels), which was further confirmed by histology. Moreover, HRI revealed the vascular changes induced by rapamycin treatment. Finally, HRI facilitates primary hepatic tumor characterization with good correlation to the pathologic differentiation. The HRI method is highly sensitive to subtle hemodynamic changes induced by CRLM and, hence, can function as an imaging tool for understanding the hemodynamic changes occurring during CRLM establishment, progression, and antiangiogenic treatment. In addition, this method facilitated the differentiation between different types of hepatic lesions based on their vascular profile noninvasively.
最近，我们已经证明了使用血流动力学反应成像（HRI）的可行性，这是一种结合高碳酸血症和高氧的功能磁共振成像（MRI）方法，无需造影剂即可监测肝病变过程中的血管变化。在这项研究中，我们评估了 HRI 评估肝肿瘤血管变化的能力，包括肿瘤建立、进展和抗血管生成治疗期间的血管变化。通过脾内注射结直肠腺癌细胞来模拟结直肠肝转移（CRLM），并使用 Mdr2 基因敲除小鼠来模拟原发性肝肿瘤。使用 HRI 方案评估肝灌注参数，并与对比增强（CE）MRI 进行比较。HRI 显示出明确的 CRLM 的低血流灌注和增加的动脉血液供应。在 CRLM 荷瘤小鼠中，由于 HRI 图谱显著减少了 35%，整个肝脏灌注均减弱。与 CE-MRI（分别为 82%和 38%）相比，该研究表明 HRI 方法对小 CRLM（1-2mm）的检测具有更高的敏感性。此外，HRI 可以显示 CRLM 进展过程中的血管变化（分支血管），这进一步通过组织学得到证实。此外，HRI 显示了雷帕霉素治疗引起的血管变化。最后，HRI 有助于原发性肝肿瘤的特征化，与病理分化具有良好的相关性。HRI 方法对 CRLM 引起的细微血流动力学变化非常敏感，因此可以作为一种成像工具，用于了解 CRLM 建立、进展和抗血管生成治疗过程中发生的血流动力学变化。此外，该方法还可以方便地根据血管特征无创地区分不同类型的肝病变。
