Liver regeneration and energetic changes in rats following hepatic radiation therapy and hepatocyte transplantation by 31P MRSI

Charles S. Landis, Hongchao Zhou, Laibin Liu, Hoby P. Hetherington, Chandan Guha

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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, 31P 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 31P 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 31P 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 31P 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.

Original languageEnglish (US)
Pages (from-to)1145-1151
Number of pages7
JournalLiver International
Volume35
Issue number4
DOIs
StatePublished - Apr 1 2015

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Liver Regeneration
Hepatocytes
Radiotherapy
Transplantation
Adenosine Triphosphate
Liver
Hepatectomy
Radiation
Liver Neoplasms
Regeneration

Keywords

  • Hepatocyte
  • MR spectroscopy
  • Radiation-induced liver damage
  • Transplantation

ASJC Scopus subject areas

  • Hepatology

Cite this

Liver regeneration and energetic changes in rats following hepatic radiation therapy and hepatocyte transplantation by 31P MRSI. / Landis, Charles S.; Zhou, Hongchao; Liu, Laibin; Hetherington, Hoby P.; Guha, Chandan.

In: Liver International, Vol. 35, No. 4, 01.04.2015, p. 1145-1151.

Research output: Contribution to journalArticle

Landis, Charles S. ; Zhou, Hongchao ; Liu, Laibin ; Hetherington, Hoby P. ; Guha, Chandan. / Liver regeneration and energetic changes in rats following hepatic radiation therapy and hepatocyte transplantation by 31P MRSI. In: Liver International. 2015 ; Vol. 35, No. 4. pp. 1145-1151.
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