title: Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes.
abstract: BACKGROUND
  Hepatic radiation toxicity restricts irradiation of liver malignancies. Better knowledge of hepatic tolerance dose is favourable to gain higher safety and to optimize radiation regimes in radiotherapy of the liver. In this study we sought to determine the hepatic tolerance dose to small volume single fraction high dose rate irradiation.
  
  
  METHODS
  23 liver metastases were treated by CT-guided interstitial brachytherapy. MRI was performed 3 days, 6, 12 and 24 weeks after therapy. MR-sequences were conducted with T1-w GRE enhanced by hepatocyte-targeted Gd-EOB-DTPA. All MRI data sets were merged with 3D-dosimetry data. The reviewer indicated the border of hypointensity on T1-w images (loss of hepatocyte function) or hyperintensity on T2-w images (edema). Based on the volume data, a dose-volume-histogram was calculated. We estimated the threshold dose for edema or function loss as the D90, i.e. the dose achieved in at least 90% of the pseudolesion volume.
  
  
  RESULTS
  At six weeks post brachytherapy, the hepatocyte function loss reached its maximum extending to the former 9.4Gy isosurface in median (i.e., ≥9.4Gy dose exposure led to hepatocyte dysfunction). After 12 and 24 weeks, the dysfunctional volume had decreased significantly to a median of 11.4Gy and 14Gy isosurface, respectively, as a result of repair mechanisms. Development of edema was maximal at six weeks post brachytherapy (9.2Gy isosurface in median), and regeneration led to a decrease of the isosurface to a median of 11.3Gy between 6 and 12 weeks. The dose exposure leading to hepatocyte dysfunction was not significantly different from the dose provoking edema.
  
  
  CONCLUSIONS
  Hepatic injury peaked 6 weeks after small volume irradiation. Ongoing repair was observed up to 6 months. Individual dose sensitivity may differ as demonstrated by a relatively high standard deviation of threshold values in our own as well as all other published data.
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg, Otto-von-Guericke-Universität Magdeburg, Germany. max.seidensticker@med.ovgu.de
authors.forename: Max
authors.initials: M
authors.lastname: Seidensticker
authors.forename: Ricarda
authors.initials: R
authors.lastname: Seidensticker
authors.forename: Konrad
authors.initials: K
authors.lastname: Mohnike
authors.forename: Christian
authors.initials: C
authors.lastname: Wybranski
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Luess
authors.forename: Maciej
authors.initials: M
authors.lastname: Pech
authors.forename: Peter
authors.initials: P
authors.lastname: Wust
authors.forename: Jens
authors.initials: J
authors.lastname: Ricke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy; D003287:Contrast Media; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008099:Liver / Q000528:radiation effects*; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000175:diagnosis; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*
chemical_list: D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA