Compartmental modeling for blood flow quantification from dynamic \(^{15}\)O-water PET images of humans: a systematic review

Dynamic positron emission tomography (PET) can be used to non-invasively estimate the blood flow of different organs via compartmental modeling. Out of different PET tracers, water labeled with the radioactive \(^{15}\)O isotope of oxygen (half-life of 2.04 min) is freely diffusable, and therefore, very well-suited for blood flow quantification. While the earlier \(^{15}\)O-water PET research has primarily focused on cerebral or myocardial blood flow quantification, the recent emergence of total-body PET scanners has enabled greater application possibilities for both PET imaging in general and also \(^{15}\)O-water PET based blood flow quantification in particular. However, to validate new methods, it is necessary to compare them to earlier research. To help in this process, we systematically review 53 articles quantifying blood flow via compartmental modeling. We introduce the articles organized within subcategories of cerebral, myocardial, renal, pulmonary, pancreatic, hepatic, muscle, and tumor blood flow and summarize their results so that they can easily be evaluated in terms of population characteristics of the patients such as age or sex ratio and their potential diagnoses. We compare how both the compartment model used and the potential corrections for arterial blood volume, non-perfusable tissue, spill-over from the heart cavities, and time delay caused while the tracer travels between different areas of interest are generally implemented in the articles. We also analyze the differences in the data pre-processing techniques. According to our results, the estimates of cerebral and tumor blood flow vary considerably more between the articles than those of myocardial blood flow. This might be caused by differences in the model approaches or the study populations. We also note that the choice of the unit for these estimates is quite inconsistent as certain researchers seem to prefer mL/min/g over mL/min/mL even if no weight or density parameter is present in the modeling. We encourage more research on sex- and age-based differences in blood flow estimates and organ-specific blood flow quantification studies for kidneys, lungs, liver, and other important organs besides brain and heart.