title: Noninvasive mapping of spontaneous fluctuations in tumor oxygenation using 19F MRI.
abstract: OBJECTIVE
  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 19F relaxometry maps to analyze the spontaneous fluctuations of partial pressure of oxygen (pO2) over time in experimental tumors.
  
  
  METHODS
  The pO2 maps were generated after direct intratumoral administration of a fluorine compound (hexafluorobenzene) whose relaxation rate (1/T1) is proportional to the % O2. The authors used a SNAP inversion-recovery sequence at 4.7 T to acquire parametric images of the T1 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 pO2 over time.
  
  
  RESULTS
  The authors were able to quantify and probe the heterogeneity of spontaneous fluctuations in tumor pO2: (i) Spontaneous fluctuations in pO2 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 19F MRI technique is sensitive to acute change in pO2 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.
authors.affiliation: Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels 1200, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Magat
authors.forename: B F
authors.initials: BF
authors.lastname: Jordan
authors.forename: G O
authors.initials: GO
authors.lastname: Cron
authors.forename: B
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D005461:Fluorine; D005583:Fourier Analysis; D007091:Image Processing, Computer-Assisted / Q000706:statistics & numerical data; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D011877:Radionuclide Imaging
chemical_list: D005461:Fluorine; D010100:Oxygen