MRI Assessment of Tumor Perfusion, Permeability and Cellularity

描述（由申请人提供）：拟议研究的总体目标是开发动态敏感性对比磁共振成像（DSC-MRI）方法，用于同时评估脑和非脑肿瘤的肿瘤灌注、通透性和细胞性，并评估其作为治疗反应的潜在替代生物标志物的作用。由于在造影剂外渗情况下获得的DSC-MRI信号的生物物理基础得到了更全面的表征，因此很明显，它们反映了其他潜在的生物学特征，如血管完整性和/或细胞结构，这与动态对比增强（DCE） MRI和扩散加权(DW)-MRI所询问的结果没有什么不同。为此，我们建议开发一种DSC- MRI方法，能够同时获取可靠的血流量和血容量测量、DCE-MRI数据和一种新的成像度量，即血管外敏感性校准因子，我们建议该因子反映细胞特征，如密度和/或间距。为了表征和验证所提出的方法，我们将比较原位脑和乳腺肿瘤模型的DSC-MRI， DCE-MRI和定量放射自显影衍生的灌注（Aim 1）和通透性（Aim 2）测量。与DW-MRI相比，基于DSC-MRI的肿瘤细胞度度量将在细胞幻象和肿瘤组织中进行表征，并使用组织学进行验证（目的3）。最后，鉴于DCE-MRI和DW-MRI在评估治疗反应方面的临床前和临床成功，我们将比较它们与拟议的成像指标的敏感性，以评估治疗引起的肿瘤血管和细胞状态的变化（目的4）。意义：所提方法的验证将能够同时获取反映灌注、渗透性和细胞度的参数，从而减少MRI总扫描时间和造影剂剂量。该方法可以有效、全面地评估肿瘤治疗反应，使DSC-MRI方法能够应用于非脑肿瘤，从而大大提高临床护理水平。

DESCRIPTION (provided by applicant): The overall goals of the proposed research are to develop dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) methods for the simultaneous assessment of tumor perfusion, permeability and cellularity in cerebral and non-cerebral tumors and to evaluate their role as potential surrogate biomarkers of treatment response. As the biophysical basis of DSC-MRI signals acquired in the presence of contrast agent extravasation is more comprehensively characterized it is evident that they reflect additional underlying biological features such as the vascular integrity and/or cellularity, not unlike those interrogated with dynamic contrast enhanced (DCE) MRI and diffusion weighted (DW)-MRI. To this end we propose to develop a DSC- MRI method that enables the simultaneous acquisition of reliable blood flow and blood volume measures, DCE-MRI data and a new imaging metric, the extravascular susceptibility calibration factor, which we propose reflects cellular features such as density and/or spacing. To characterize and validate the proposed method we will compare DSC-MRI, DCE-MRI and quantitative autoradiography derived measures of perfusion (Aim 1) and permeability (Aim 2) in orthotopic brain and breast tumor models. The DSC-MRI based tumor cellularity metric will be characterized in cellular phantoms and tumor tissue, compared with DW-MRI and validated using histology (Aim 3). Finally, given the pre-clinical and clinical success of DCE-MRI and DW-MRI to assess treatment response, we will compare their sensitivity to that of the proposed imaging metrics to asses treatment induced changes in tumor vascular and cellular status (Aim 4). Significance: The validation of the proposed methods would enable the simultaneous acquisition of parameters reflecting perfusion, permeability and cellularity thereby reducing total MRI scan time and contrast agent dose. Such an approach could greatly enhance clinical care by providing an efficient and more comprehensive assessment of tumor treatment response and enabling the application of DSC-MRI methods to non-cerebral tumors. PUBLIC HEALTH RELEVANCE: The proposed research focuses on the development of magnetic resonance imaging methods that provide a more efficient and complete assessment of a tumor's response to treatment. Such methods could decrease health care costs, contrast agent dose and improve the way treatments are planned and monitored.