Overhauser Enhanced Magnetic Resonance Imaging (OMRI)

项目二：检修用户增强磁共振成像。（OMRI）肿瘤微血管结构和功能异常导致肿瘤存在缺氧，实体瘤的这一特点对化疗和放疗具有耐药性，导致预后不良。超极化诱导1H-H2O强烈依赖于体内氧敏感造影剂TAM周围的氧水平。成功提取这种氧依赖的OMRI信号增强，提供了SCC荷瘤小鼠的定量氧图谱。该技术的进一步扩展是利用氧探针TAM本身作为微血管通透性的标志。与药代动力学模型相匹配的动态OMRI扫描数据提供了内皮传递常数Ktrans图作为微血管通透性的标志，同时还提供了氧制图。基于像素的pO2与Ktrans的x-y图显示负相关，这意味着肿瘤随着血管渗漏而变得缺氧。15gy放射治疗前后的纵向OMRI扫描可以检测到辐射诱导的肿瘤微血管变化，这可以从放射前获得的氧图中预测。这些结果提示，上述肿瘤氧和微血管通透性同时成像技术具有无创预测和监测放疗疗效的潜力。大多数肿瘤诊断成像依赖于在人类癌症中广泛观察到的共同表型。有氧糖酵解也是临床FDG-PET的基础之一。13c标记的丙酮酸在放置在扫描仪外的偏振器中进行超极化，使其13C-MRI灵敏度提高了10,000倍以上，使我们能够通过典型的MRI成像外用13c -丙酮酸及其代谢物的分布。与正常组织不同，肿瘤更倾向于有氧糖酵解而不是氧化磷酸化，从而导致丙酮酸产生过量的乳酸。虽然是初步的，但我们已经观察到，在超极化13c -丙酮酸注射后，SCC荷瘤小鼠产生了显著的乳酸。我们未来的研究将把这种肿瘤代谢图像与我们已经通过EPR成像和OMRI建立的肿瘤氧制图结合起来，这有助于更好地了解肿瘤氧状态与其葡萄糖代谢的关系。常规MRI肿瘤代谢成像的可行性将为肿瘤诊断提供一个新的维度。

Project 2: Overhauser enhanced Magnetic Resonance Imaging. (OMRI) Structural and functional abnormality of tumor microvasculature contributes to existent tumor hypoxia, and this feature of solid tumor shows resistance to chemotherapy and radiotherapy, resulting in poor prognosis. Hyperpolarization induction of 1H-H2O strongly depends on the oxygen level surrounding the oxygen sensitive contrast agent TAM in the body. Successful extraction of this oxygen dependent OMRI signal enhancement confers the quantitative oxygen maps in SCC tumor bearing mice. Further extension of this technique is to utilize the oxygen probe TAM itself as a marker of microvascular permeability. Dynamic OMRI scan data fitted to pharmacokinetic models provides endothelial transfer constant Ktrans map as a marker of microvascular permeability, simultaneously with oxygen mapping. Pixel based x-y plot of pO2 vs. Ktrans show the negative correlation, meaning that tumors become hypoxic along with their vasculature becoming leaky. Longitudinal OMRI scans before and after 15 Gy radiation therapy results in the detection of radiation-induced tumor microvascular change, which can be predicted from the oxygen map obtained before the radiation. These findings suggests that the above mentioned simultaneous imaging technique of tumor oxygen and microvascular permeability has the potential to predict and monitor the efficacy of radiation therapy in a non-invasive way. Most tumor diagnostic imaging depends on the common phenotypes that are widely observed in human cancer. Aerobic glycolysis is one of such phenotypes on which clinical FDG-PET also based. Hyperpolarization of 13C-labeled pyruvic acid in the polarizer placed outside the scanner increases its 13C-MRI sensitivity greater than 10,000 times that make us to image the distribution of externally administrated 13C-pruvic acid and its metabolite by a typical MRI. Tumors, unlike normal tissues, prefer aerobic glycolysis than oxidative phosphorylation, resulting in excess lactate production from pyruvate. Though preliminary, we have observed significant lactate production in SCC tumor bearing mice after hyperpolarized 13C-pyruvic acid injection. Our future study will combined this tumor metabolic image with tumor oxygen mapping, which we have already established by both EPR imaging and OMRI, that help to better understand the relationship between tumor oxygen status and its glucose metabolism. Feasibility of tumor metabolic imaging using conventional MRI would provide a new dimension for tumor diagnosis.