title: Liver regeneration and energetic changes in rats following hepatic radiation therapy and hepatocyte transplantation by ³¹P MRSI.
abstract: OBJECTIVE
  Radiation-induced liver damage (RILD) is a poorly understood and potentially devastating complication of hepatic radiation therapy (RT) for liver cancers. Previous work has demonstrated that hepatocyte transplantation (HT) can ameliorate RILD in rats. We hypothesized that RT inhibits generation of cellular ATP and suppresses hepatic regeneration.
  
  
  METHODS
  To study the metabolic changes that occur in RILD with and without HT, (31)P MRSI data were acquired in rats treated with partial hepatectomy (PH) alone, PH with hepatic irradiation (PHRT) or PHRT with HT (PHRT+HT).
  
  
  RESULTS
  Both [γ -ATP] and ATP/Pi (31)P MRSI signal ratio initially decreased and subsequently returned to baseline levels within 2 weeks after PH, which is consistent with other published data. Persistently reduced [γ-ATP] and ATP/Pi (31)P MRSI signal ratio were observed in rats up to 20 weeks after PHRT. However, progressive increases in [γ -ATP] were observed over time in the group of rats receiving PHRT+HT. Normal [γ -ATP] was observed 20 weeks after PHRT+HT (vs. PH alone), although, ATP/Pi levels did not return to normal after PHRT +HT. Ex vivo histological studies were performed to confirm liver repopulation with transplanted hepatocytes and the amelioration of pathologic changes of RILD.
  
  
  CONCLUSIONS
  These findings suggest that (31)P MRSI can be used to monitor the progress of RILD and its amelioration using transplanted hepatocytes to simultaneously restore metabolic function while replacing host hepatocytes damaged by RT.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Landis
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhou
authors.forename: Laibin
authors.initials: L
authors.lastname: Liu
authors.forename: Hoby P
authors.initials: HP
authors.lastname: Hetherington
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D004734:Energy Metabolism; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011916:Rats, Inbred F344; D020127:Recovery of Function; D013997:Time Factors
chemical_list: D000255:Adenosine Triphosphate
keywords: MR spectroscopy; hepatocyte; radiation‐induced liver damage; transplantation