Review of methods used to study oxygen transport at the microcirculatory level.

The existence of hypoxic regions in tumors has long been recognized as a key factor leading to radiation resistance. More recently, it has been found that low oxygen levels also affect drug resistance, angiogenesis, cytokine production, cell cycle control, apoptosis, and metastatic propensity of tumors. Until now, most approaches to eliminating hypoxia have been empirical. However, improved understanding of the underlying mechanisms may permit the development of more soundly based, effective approaches. As discussed in this review, critical evaluation of the factors governing oxygen transport in tumors requires a thorough understanding of the methods used to study this process. Many experimental methodologies can be used to address these issues. In this review, the emphasis is placed on techniques that measure parameters on the scale of the diffusion distance of oxygen. Studies at the microregional level provide the most detailed physiological information on such processes. Over the past few years, significant progress in technology has allowed us to measure tumor oxygenation, yet spatial and temporal heterogeneities continue to provide significant challenges to obtaining clear knowledge of oxygen transport.