title: Correlating quantitative MR measurements of standardized tumor lines with histological parameters and tumor control dose.
abstract: OBJECTIVE
  To correlate non-invasively acquired radiobiologically relevant magnetic resonance (MR) parameters with functional histology and tumor control doses (TCD(50)).
  
  
  METHODS
  The MR parameters relative perfusion, re-oxygenation and lactate (Lac) concentration from eight human xenograft squamous tumor lines were compared with the histologically acquired pimonidazole hypoxic fraction, the perfused vessel area and TCD(50).
  
  
  RESULTS
  Good spatial correlation in the parameter maps could be observed between the pimonidazole staining and tumor regions, which can be reoxygenated when breathing carbogen. A strong positive correlation (R=0.74) was found between whole tumor pimonidazole hypoxic fraction and re-oxygenation, as one would expect. A good correlation was also observed between Lac concentration and re-oxygenation (R=0.71) and between TCD(50) and re-oxygenation (R=0.64), whereas Lac and TCD(50) showed a moderate relation (R=0.44). The in vivo measurement of relative perfusion could be validated to reflect the perfused vessel area (R=0.63). No correlation was detected between perfusion and re-oxygenation or TCD(50).
  
  
  CONCLUSIONS
  Lac and re-oxygenation were shown to be pretreatment predictive markers independent from the pathophysiological changes induced during a fractionated course of radiotherapy. These parameters hold promise to be acquired non-invasively with results just a few minutes after measurement and to tailor radiotherapy to individual patterns of a tumor microenvironment.
authors.affiliation: Department of Physics, University of Würzburg, Würzburg, Germany. moerchel@physik.uni-wuerzburg.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Mörchel
authors.forename: Gerd
authors.initials: G
authors.lastname: Melkus
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jakob
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000528:radiation effects; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism* / Q000528:radiation effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009593:Nitroimidazoles / Q000494:pharmacology; D010101:Oxygen Consumption / Q000528:radiation effects; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D019344:Lactic Acid; C033815:pimonidazole