Overhauser Enhanced Magnetic Resonance Imaging (OMRI)

奥豪瑟增强磁共振成像 (OMRI)

• 批准号: 8349014
• 负责人: murali cherukuri
• 金额: $ 49.38万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349014
• 关键词: Aftercare; Angiogenesis Inhibitors; Animals; Biochemical; Cell Nucleus; Chemical Shift Imaging; Chemicals; Cytostatics; Dependence; Detection; Early treatment; Echo-Planar Imaging; Image; Injection of therapeutic agent; Label; Magnetic Resonance Imaging; Magnetism; Measures; Metabolic; Metabolism; Mitochondria; Monitor; Nature; PDH kinase; Physiologic pulse; Physiology; Protons; Pyruvate; Radiation; Radiation therapy; Signal Transduction; Techniques; Tracer; Up-Regulation; Water; Western Blotting; Work; aerobic glycolysis; base; cancer therapy; cytotoxic; data acquisition; density; irradiation; molecular imaging; response; spectroscopic imaging; time interval; treatment effect; treatment response; tumor

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.

1）快速的化学移位成像：13C标记示踪剂的超极化MRI是一种新兴技术，可无创地可视化外源注射的底物的代谢，例如13C标记的丙酮酸。由于超极化丙酮酸的MRI信号持续时间少于2分钟，因此根据对动物注射示踪剂的Pharamacokinics的假设进行了早期工作，或者在动物中注射示踪剂或注入示踪剂以获取此类信息以获取此类信息，然后进行第二次注射代谢成像。为了克服这一问题，并进行了Pharamacokinetic评估以及代谢成像，我们开发并实施了快速的化学转移成像能力。基于注射过高的13C-MRI超极化13C-MRI的回声平面成像序列NMR信号在注射后仅持续2-3分钟，并且目前基于梯度的化学移位成像（CSI）（CSI）需要15-20秒才能获得数据获取的15-20秒，以至于足够快地跟踪动力学的动力学。我们已经开发并优化了基于回声平面的光谱成像（EPSI）的MRI脉冲序列，现在可以每2-5秒获得2D代谢图像。 2。检测对抗血管生成治疗的早期治疗反应。癌症治疗反应的典型标准不能应用于细胞毒性的抗血管生成疗法。我们已经研究了丙酮酸超极化的13C MRI是否可以检测SCCVII肿瘤对抗血管生成药物舒尼替尼的反应。丙酮酸到乳酸转化的通量显着放缓2和舒尼尼治疗后4天，蛋白质印迹分析表明，丙酮酸脱氢酶激酶-1（PDK-1）的降低机制，以及导致的线粒体型丙二酸酯使用的上调。 3。检测肿瘤对放射治疗的反应，我们还应用了丙酮酸代谢成像以检测对辐射的治疗反应。 10GY X辐射后，肿瘤丙酮酸乳酸转化率暂时增加了24小时，然后降低了连续3个10GY/天（总30GY）辐射的连续3个部分。我们正在研究放射治疗后这种丙酮酸代谢变化的潜在机制。