MRI Assessment of Tumor Perfusion, Permeability and Cellularity

肿瘤灌注、渗透性和细胞结构的 MRI 评估

• 批准号: 8703037
• 负责人: Christopher Chad Quarles
• 金额: $ 30.77万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703037
• 关键词: Acceleration; Aminoisobutyric Acids; Animals; Area; Asses; Biological; Biological Markers; Blood; Blood Vessels; Blood Volume; Blood flow; Brain; Brain Neoplasms; Calibration; Cell Density; Cells; Cellularity; Cerebral Neoplasm; Clinical; Clinical Trials; Complex; Contrast Media; Data; Development; Diffusion Magnetic Resonance Imaging; Dose; Erythrocytes; Extravasation; Goals; Gold; Growth; Health Care Costs; Healthcare; Histology; Image; In Vitro; Label; Lead; MRI Scans; Magnetic Resonance Imaging; Mammary Neoplasms; Maps; Measurement; Measures; Methods; Metric; Modeling; Monitor; Perfusion; Permeability; Predisposition; Quantitative Autoradiography; Relative (related person); Relaxation; Research; Role; Signal Transduction; Standardization; Surface; Technetium 99m; Time; Tissues; Tumor Tissue; Validation; Vascular Permeabilities; base; brain tissue; chemotherapy; clinical care; data acquisition; density; hemodynamics; imaging modality; improved; in vivo; in vivo imaging; pre-clinical; response; success; treatment planning; treatment response; tumor

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.

描述(申请人提供)：拟议研究的总体目标是开发动态磁化率对比磁共振成像(DSC-MRI)方法，用于同时评估脑肿瘤和非脑肿瘤的肿瘤灌注、渗透性和细胞性，并评估它们作为潜在的替代治疗反应生物标志物的作用。由于在存在造影剂外溢的情况下获得的DSC-MRI信号的生物物理基础得到了更全面的表征，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/或细胞密度，与动态增强(DCE)MRI和弥散加权(DW)MRI所询问的相似。为此，我们建议开发一种DSC-MRI方法，该方法能够同时获取可靠的血流和血容量测量、DCE-MRI数据和一种新的成像指标-血管外敏感性校准因子，我们建议使用该指标来反映细胞特征，如密度和/或间距。为了表征和验证所提出的方法，我们将在原位脑肿瘤和乳腺肿瘤模型中比较DSC-MRI、DCE-MRI和定量放射自显影测量的灌注(AIM 1)和通透性(AIM 2)。与DW-MRI相比，基于DSC-MRI的肿瘤细胞密度度量将在细胞模体和肿瘤组织中进行表征，并使用组织学进行验证(AIM 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上的成功，我们将比较它们与建议的成像指标在评估治疗引起的肿瘤血管和细胞状态变化方面的敏感性(目标4)。意义：所提出的方法的验证将使得能够同时获取反映灌注、渗透性和细胞密度的参数，从而减少总的MRI扫描时间和造影剂用量。这种方法可以通过提供对肿瘤治疗反应的有效和更全面的评估，并使DSC-MRI方法能够应用于非脑肿瘤，从而极大地加强临床护理。