Dartmouth College, Hanover, NH, USA.
Department of Radiation Oncology, University Medical Center, University of Freiburg/Brsg., Freiburg, Germany.
Adv Exp Med Biol. 2024;1463:307-314. doi: 10.1007/978-3-031-67458-7_50.
Measuring oxygen (O) in tissues has been a central theme of the International Society on Oxygen Transport to Tissue (ISOTT) since its founding 50 years ago in 1973. The initial presentations by many distinguished members reflect this focus and demonstrate the importance of the contributions of the members of ISOTT. This paper considers their work and its legacy in the context of the continuing challenges of making meaningful measurements of O in tissue. Because many technical, physiological, and pathophysiological factors are directly or implicitly involved in obtaining any measured value of O in living tissues, interpretations of what the measured value represents and its biological implications need to take these factors into account. The challenges arise from two very simple but painfully true factors that make it challenging to obtain measurements of O in tissues in vivo that are useful for the understanding of physiological and pathophysiological processes. First, throughout the volume of functioning tissue that is assessed by any technique, there is a complex spatial heterogeneity of O levels. No technique can usually fully represent this complexity in a given measurement, because the heterogeneity extends from the environment in the tissue surrounding cells to variations within the cell. Therefore, the value of the output from a measurement inevitably consists of a complex, averaged summary of O in the tissue. Second, the levels of O are constantly changing in living tissues (variations occur in seconds, minutes, hours, and/or days and differ by location) at rates that are difficult to resolve for available techniques, because they occur faster than data acquisition time and/or cannot be used as frequently as needed to follow the longer-term changes. However, as demonstrated in research reported in the publications from ISOTT, studies of O in tissue, in spite of the potential ambiguities in the measured values, can provide very valuable insights into physiology and pathophysiology. This is most likely to occur if researchers explicitly recognise why and how their measurement does not fully portray the complexity of O. When measurements can be repeated, the resulting change between measurements provides information about the dynamics of the physiology and pathophysiology. Assessing change in O levels can also provide evidence about responses to treatments. Similarly, finding evidence of hypoxia, even though it does not capture the heterogeneity and dynamics actually happening in the tissue, can still inform clinical care if the measurement is well-understood.
测量组织中的氧气（O）一直是国际组织氧气输送到组织（ISOTT）的核心主题，该组织成立于 50 年前的 1973 年。许多杰出成员的最初介绍反映了这一重点，并展示了 ISOTT 成员的贡献的重要性。本文考虑了他们的工作及其在组织中 O 进行有意义测量的持续挑战背景下的遗产。由于许多技术、生理和病理生理因素直接或间接地涉及到对活组织中任何测量的 O 值的获取，因此对所测量值的解释及其生物学意义需要考虑到这些因素。挑战来自两个非常简单但又非常真实的因素，这使得在体内组织中获得有用的生理和病理生理过程的 O 测量变得具有挑战性。首先，在任何技术评估的整个功能组织体积中，O 水平存在复杂的空间异质性。通常，由于异质性从细胞周围组织的环境延伸到细胞内的变化，因此没有一种技术可以在给定的测量中完全代表这种复杂性。因此，测量结果的输出值不可避免地是组织中 O 的复杂平均总结。其次，活组织中的 O 水平不断变化（变化发生在几秒钟、几分钟、几小时和/或几天内，并且因位置而异），现有技术难以解决这些变化的速度，因为它们发生的速度比数据采集时间快，或者不能像需要的那样频繁地用于跟踪较长时间的变化。然而，正如 ISOTT 出版物中报道的研究所示，尽管在测量值中存在潜在的模糊性，但对组织中的 O 进行研究可以为生理学和病理生理学提供非常有价值的见解。如果研究人员明确认识到他们的测量为什么以及如何不能完全描绘 O 的复杂性，这就最有可能发生。当可以重复测量时，测量之间的变化提供了有关生理学和病理生理学动态的信息。评估 O 水平的变化也可以提供有关治疗反应的证据。同样，如果对测量有很好的了解，即使它没有捕获组织中实际发生的异质性和动态，发现缺氧的证据仍然可以为临床护理提供信息。
