Small Animal In vivo quantification of cerebral glucose metabolic rate

小动物体内脑葡萄糖代谢率定量

• 批准号: 7471287
• 负责人: Christine Hsiao-Ming Wu
• 金额: $ 16.84万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7471287
• 关键词: Acute; Animal Disease Models; Animal Model; Animals; Arterial Lines; Autoradiography; Blood; Blood specimen; Brain; Brain Mapping; Brain imaging; Central Nervous System Diseases; Cerebrum; Clinic; Clinical; Cognitive; Communities; Condition; Count; Development; Devices; Disease; Edema; End Point; Experimental Models; Glucose; Goals; Heart; Hematoma; Image; Imaging Device; Imaging Techniques; Infection; Injury; Invasive; Isotopes; Kinetics; Knowledge; Left ventricular structure; Link; Manuals; Maps; Measurement; Measures; Mental Depression; Metabolic; Metabolism; Methodology; Methods; Microfluidic Microchips; Microfluidics; Modality; Modeling; Monitor; Numbers; Operative Surgical Procedures; Outcome; Pathology; Patient Monitoring; Plasma; Plasma Cells; Positron-Emission Tomography; Procedures; Process; Public Health; Radiation; Rate; Rattus; Recovery; Recovery of Function; Reproducibility; Research; Research Personnel; Safety; Sampling; Scanning; Simulate; Standards of Weights and Measures; TBI Patients; Techniques; Technology; Time; Tracer; Translational Research; Trauma; Traumatic Brain Injury; Venous; base; clinically relevant; cost; day; glucose uptake; heart imaging; improved; in vivo; prototype; radiotracer; tool; uptake

DESCRIPTION (provided by applicant): Positron emission tomography (PET) is widely used to map the cerebral metabolic rate of glucose (CMRG) and is widely used to indicate cognitive and outcome status in the clinical arena. However, use of this imaging modality in clinically relevant small animal models of disease remains infrequent, and the majority of microPET imaging studies remain non-quantitative. Major impediments to more wide-spread use of quantitative microPET include blood sampling requirements. Solving the methodological issues that have limited the utility of small animal PET imaging for accurate and repeated quantitative measurements of CMRG will provide an important tool to enhance research in a variety of disease states. Studies are proposed to improve in vivo, multi-time-point quantification of CMRG by integrating small animal microPET with microfluidic plasma sampling technology. In vivo CMRG values determined using this automated microfluidics methodology will be compared against those determined using traditional, manually drawn sampling methods in the same animals. A second microPET study will determine the accuracy and utility of a minimally-invasive method of simultaneous measurement of blood and brain glucose isotope concentration. Since PET imaging is used so extensively in the neurosurgical clinic to monitor patients with traumatic brain injury (TBI) we will conduct a proof-of-principle study using the optimal microPET methods determined in our second microPET study to quantify the acute post-injury depression of CMRG and its recovery in an experimental model of mild-moderate unilateral TBI in rats. The accuracy and reliability of microPET-based CMRG values will be compared against values derived from end-point standard autoradiography methods. Successful completion of the proposed research will make multi-time-point, quantitative microPET imaging of small animals safe and routinely feasible. This will represent a major advance in the utility of this important translational research tool and should enhance progress in the monitoring and development of potential therapies for treatment of TBI and other diseases of the central nervous system. PUBLIC HEALTH RELEVANCE: The studies will be performed to improve the safety and reliability and to reduce the number of invasive procedures needed to conduct quantitative imaging of brain glucose utilization in small animals. A new automated plasma sampling device that is capable of taking very small samples of blood as well as separating plasma from the blood cells will be developed and integrated into current brain imaging procedures. Rates of brain glucose use will be calculated, comparing the values obtained in calculations using blood plasma samples or a single plasma sample in combination with imaging glucose uptake in both heart and brain. The optimal imaging method will be used to monitor changes in brain glucose use over time in rats with experimental traumatic brain injury. Upon completion of this project a new imaging tool will be available to researchers to study brain function under physiologically stable conditions with minimal radiation exposure.

描述（由申请人提供）：正电子发射断层扫描（PET）广泛用于绘制大脑葡萄糖代谢率（CMRG）图，并广泛用于指示临床领域的认知和结果状态。然而，这种成像方式在临床相关的小动物疾病模型中的使用仍然很少，并且大多数 microPET 成像研究仍然是非定量的。更广泛使用定量 microPET 的主要障碍包括血液采样要求。解决限制小动物 PET 成像准确、重复定量测量 CMRG 的方法学问题，将为加强各种疾病状态的研究提供重要工具。建议通过将小动物 microPET 与微流控血浆采样技术相结合来改善 CMRG 的体内多时间点定量。使用这种自动微流体方法确定的体内 CMRG 值将与在同一动物中使用传统的手动采样方法确定的值进行比较。第二项 microPET 研究将确定同时测量血液和脑葡萄糖同位素浓度的微创方法的准确性和实用性。由于 PET 成像在神经外科诊所中广泛用于监测创伤性脑损伤 (TBI) 患者，我们将使用第二项 microPET 研究中确定的最佳 microPET 方法进行原理验证研究，以量化急性损伤后抑郁症CMRG 及其在大鼠轻中度单侧 TBI 实验模型中的恢复。基于 microPET 的 CMRG 值的准确性和可靠性将与终点标准放射自显影方法得出的值进行比较。拟议研究的成功完成将使小动物的多时间点定量 microPET 成像安全且常规可行。这将代表这一重要转化研究工具的实用性取得重大进展，并应促进治疗 TBI 和其他中枢神经系统疾病的潜在疗法的监测和开发进展。公共健康相关性：进行这些研究的目的是提高安全性和可靠性，并减少对小动物脑葡萄糖利用进行定量成像所需的侵入性操作的数量。将开发一种新的自动血浆采样装置，该装置能够采集非常小的血液样本并将血浆与血细胞分离，并将其集成到当前的脑成像程序中。将计算脑葡萄糖使用率，比较使用血浆样本或单个血浆样本与心脏和大脑中葡萄糖摄取成像相结合的计算中获得的值。最佳成像方法将用于监测实验性脑外伤大鼠脑葡萄糖使用随时间的变化。该项目完成后，研究人员将可以使用一种新的成像工具来研究生理稳定条件下、辐射暴露最少的大脑功能。