Measurement of input functions in rodents: challenges and solutions
Measurement of input functions in rodents: challenges and solutions
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DOI：
10.1016/j.nucmedbio.2005.06.012
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发表时间：
2005-10-01
影响因子：
3.1
通讯作者：
Welch, MJ
中科院分区：
文献类型：
--
作者：
Laforest, R;Sharp, TL;Welch, MJ
简介：示踪动力学模型与正电子发射断层扫描 (PET) 结合使用，是对生理、生物和分子过程及其因疾病引起的变化进行无创量化的绝佳工具。目前，复杂的多室建模方法正在应用于各种临床研究，以确定正常和患病心脏的心肌灌注、活力和葡萄糖利用率以及脂肪酸代谢和氧化。这些动力学模型需要随时间变化的示踪剂活性的两个关键测量：动脉血中的示踪剂活性（输入函数）及其在感兴趣的器官中的相应活性。当示踪剂活性从血液行进到感兴趣的器官时，示踪剂活性的时间过程的变化描述了示踪剂的动力学。为了能够使用小动物 PET (microPET) 在啮齿动物疾病模型中实施这些方法，必须准确测量输入函数。方法：啮齿动物实验中的血液输入函数通过以下方式获得：(1) 直接血液采样，(2) 通过计算血液中活性的 β 检测探针直接测量血液活性，(3) 动静脉旁路（AN 分流），(4) 对动态 PET 图像的动态结构进行因子分析，以及 (5) 测量来自动态 PET 图像的感兴趣区域 (ROI) 分析。以直接采血作为参考标准，与其他技术的结果进行比较。结果：Beta探针操作困难，并且可能无法提供准确的血液输入功能，除非静脉内使用，这需要复杂的显微手术。类似的限制也适用于 AN 分流器。因子分析成功提取了小鼠和大鼠的血液输入函数。由于PET系统图像分辨率有限，基于ROI的方法精度较低，导致严重的部分容积效应和心肌溢出。结论：目前的参考标准，直接采血，侵入性较大，时间分辨率有限。利用当前的成像技术，可以通过因子分析基于图像提取血液输入函数，而未来的技术发展可能允许直接从图像中提取输入函数。这些技术将降低动物实验的复杂性和侵入性，并且可能在未来得到更广泛的应用。 (c) 2005 Elsevier Inc. 保留所有权利。
Introduction: Tracer kinetic modeling used in conjunction with positron emission tomography (PET) is an excellent tool for the noninvasive quantification of physiological, biological and molecular processes and their alterations due to disease. Currently, complex multicompartment modeling approaches are being applied in a variety of clinical studies to determine myocardial perfusion, viability and glucose utilization as well as fatty acid metabolism and oxidation in the normal and diseased heart. These kinetic models require two key measurements of tracer activity over time, tracer activity in arterial blood (input function) and its corresponding activity in the organ of interest. The alteration in the time course of tracer activity as it travels from blood to the organ of interest describes the kinetics of the tracer. To be able to implement these approaches in rodent models of disease using small-animal PET (microPET), it is imperative that the input function is measured accurately.Methods: The blood input functions in rodent experiments were obtained by (1) direct blood sampling, (2) direct measurement of blood activity by a beta-detecting probe that counts the activity in the blood, (3) an arterial-venous bypass (AN shunt), (4) factor analysis of dynamic structures from dynamic PET images and (5) measurement from region-of-interest (ROI) analysis of dynamic PET images. Direct blood sampling was used as the reference standard to which the results of the other techniques were compared.Results: Beta probes are difficult to operate and may not provide accurate blood input functions unless they are used intravenously, which requires complicated microsurgery. A similar limitation applies to the AN shunt. Factor analysis successfully extracts the blood input function for mice and rats. The ROI-based method is less accurate due to limited image resolution of the PET system, which results in severe partial volume effect and spillover from myocardium.Conclusion: The current reference standard, direct blood sampling, is more invasive and has limited temporal resolution. With current imaging technology, image-based extraction of blood input functions is possible by factor analysis, while forthcoming technological developments are likely to allow extraction of input function directly from the images. These techniques will reduce the level of complexity and invasiveness for animal experiments and are likely to be used more widely in the future. (c) 2005 Elsevier Inc. All rights reserved.