Noninvasive mapping of spontaneous fluctuations in tumor oxygenation using F 19 MRI

Purpose: Acute hypoxia (transient cycles of hypoxia-reoxygenation) is known to occur in solid tumors and may be a poorly appreciated therapeutic problem as it can be associated with resistance to radiation therapy, impaired delivery of chemotherapeutic agents, or metastasis development. The objective of the present study was to use MR F 19 relaxometry maps to analyze the spontaneous fluctuations of partial pressure of oxygen ( pO 2 ) over time in experimental tumors. Methods: The pO 2 maps were generated after direct intratumoral administration of a fluorine compound (hexafluorobenzene) whose relaxation rate ( 1 / T 1 ) is proportional to the % O 2 . The authors used a SNAP inversion-recovery sequence at 4.7 T to acquire parametric images of the T 1 relaxation time with a high spatial and temporal resolution. Homemade routines were developed to perform regions of interest analysis, as well as pixel by pixel analysis of pO 2 over time. Results: The authors were able to quantify and probe the heterogeneity of spontaneous fluctuations in tumor pO 2 : (i) Spontaneous fluctuations in pO 2 occurred regardless of the basal oxygenation state (i.e., both in oxygenated and in hypoxic regions) and (ii) spontaneous fluctuations occurred at a rate of 1 cycle/12–47 min. For validation, the analysis was performed in dead mice for which acute changes did not occur. The authors thereby demonstrated that F 19 MRI technique is sensitive to acute change in pO 2 in tumors. Conclusions: This is the first approach that allows quantitative minimally invasive measurement of the spontaneous fluctuations of tumor oxygenation using a look-locker approach (e.g., SNAP IR). This approach could be an important tool to characterize the phenomenon of tumor acute hypoxia, to understand its physiopathology, and to improve therapies.