Recognising Potential Ambiguities in Measurements of Oxygen in Tissues.

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.