Overhauser Enhanced Magnetic Resonance Imaging (OMRI)

1)快速化学位移成像：13C标记示踪剂的超极化MRI是一种无创显示外源性注射底物(如13C标记的丙酮酸)代谢的新兴技术。由于来自超极化丙酮酸的MRI信号持续的时间间隔不到2分钟，早期的工作是基于以下假设进行的：注射示踪剂在动物体内的药代动力学或注射示踪剂以获得此类信息，然后第二次注射进行代谢成像。为了克服这一问题，同时进行药物动力学评估和代谢成像，我们开发并实施了快速化学位移成像功能。基于超极化~(13)C-MRI的回声平面成像序列，超极化~(13)C标记物的核磁共振信号在注射后仅持续2-3分钟，而现有的基于梯度回波的化学位移成像(CSI)需要15-20秒的数据采集，不足以跟踪代谢的动力学。我们已经开发和优化了基于回波平面的光谱成像(EPSI)的MRI脉冲序列，现在可以每2-5秒获得2D代谢图像。2.抗血管生成治疗早期治疗反应的检测。肿瘤治疗反应的典型标准不能应用于细胞抑制而不是细胞毒性的抗血管生成治疗。我们研究了丙酮酸的超极化~(13)C磁共振成像是否能检测到SCCVII肿瘤对抗血管生成药物舒尼替尼的反应。Sonitinib治疗后第2天和第4天，丙酮酸到乳酸的转化流量显著减慢，Western印迹分析表明，丙酮酸脱氢酶激酶-1(PDK-1)表达减少，导致线粒体丙酮酸使用量上调是其潜在机制。3.肿瘤放射治疗反应的检测我们还应用了丙酮酸代谢显像法检测肿瘤对放射治疗的反应。肿瘤丙酮酸-乳酸转化率在10Gyx射线照射后24小时一过性升高，然后连续3次10Gy日照射(共30Gy射线)后下降。我们正在研究放射治疗后丙酮酸代谢变化的潜在机制。

1) Rapid Chemical Shift Imaging: Hyperpolarized MRI of 13C-labeled tracers is an emerging technique to non-invasively visualize metabolism of exogenously injected substrates such as 13C labeled pyruvate. Since the MRI signal from the hyperpolarized pyruvate lasts for time intervals less than 2 minutes, earlier work was conducted based on assumptions of the pharamacokinetics of the injected tracer in the animal or injecting the tracer to obtain such information followed by a second injection for metabolic imaging. To overcome this problem and conduct both pharamacokinetic assessment as well as metabolic imaging, we developed and implemented rapid chemical shift imaging capabilities. Based on an Echo planar imaging sequence for hyperpolarized 13C-MRI The NMR signal of hyperpolarized 13C-labeled agents lasts only 2-3 min after injection, and currently available gradient echo based chemical shift imaging (CSI), which takes 15-20 sec for data acquisition, is not fast enough to trace the dynamics of the metabolism. We have developed and optimized the MRI pulse sequence of echo planar based spectroscopic imaging (EPSI), which can now obtain 2D metabolic images every 2-5 sec. 2. Detection of early treatment response to anti-angiogenic therapy. Typical criteria for cancer treatment response can not to applied to anti-angiogenic therapy which is cytostatic than cytotoxic. We have investigated if hyperpolarized 13C MRI of pyruvate can detect the response of SCCVII tumor to anti-angiogenic drug sunitinib. Flux of pyruvate-to-lactate conversion significantly slowdown 2 and 4 days after sunitinib treatment, and western blot analysis suggested the underlying mechanism of decreased pyruvate dehydrogenase kinase-1 (PDK-1) expression and resultant up-regulation of mitochondrial pyruvate usage. 3. Detection of tumor response to radiation therapy We also applied the pyruvate metabolic imaging to detect treatment response to radiation. Tumor pyruvate-lactate conversion rate transiently increased 24 hr after 10Gy x-irradiation, then decreased continuous 3 fractions of 10Gy/day (total 30Gy) irradiation. We are investigating underlying mechanism of this pyruvate metabolic change after radiation therapy.