title: Persistent T2*-hypointensity of the liver parenchyma after irradiation to the SPIO-accumulated liver: An imaging marker for responses to radiotherapy in hepatic malignancies.
abstract: To determine whether T2*-weighted MRI has the ability to visualize the irradiated liver parenchyma and liver tumor after irradiation to the previously superparamagnetic iron oxide (SPIO)-accumulated liver.
  
  
  
  We examined 24 liver tumor-bearing rats. Nine rats (Group 1) received 20 µmol Fe/kg SPIO and subsequent 70-Gy irradiation to the tumor-bearing liver lobe. Four rats (Group 2) received SPIO and sham irradiation. Six rats (Group 3) received saline and irradiation. Finally, five rats (Group 4) received saline and sham irradiation. We acquired sequential 3 Tesla T2*-weighted images of the liver on day 7, and assessed MR image findings including signal intensity of the tumors and tumor-bearing liver lobes.
  
  
  
  In six rats in Group 1, tumors shrunk by 39-100% (303-0 mm3), and severely, well-defined hypointense irradiated areas were observed. In the other two rats, tumors enlarged by 25 and 172% (595 and 1148 mm3), and hypointense rings surrounded the tumors. The normalized relative signal intensity of the irradiated areas was significantly lower than that of the tumor (0.53 ± 0.06 versus 0.94 ± 0.06; P < 0.05). The severely, well-defined hypointense areas were not observed in the other groups. Histologically, necrotic regions dominated and minimal nonnecrotic tumor cells remained in irradiated areas. The number of CD68-positive cells was higher in irradiated areas than in nonirradiated areas.
  
  
  
  T2*-weighted MR imaging visualized the irradiated liver parenchyma as markedly, well-defined hypointense areas and liver cancer lesions as hyperintense areas only when SPIO was administered before irradiation. The visualization of the hypointense area was associated with tumor regression after irradiation.
  
  
  
  2 J. Magn. Reson. Imaging 2017;45:303-312.
authors.affiliation: Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.|Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Furuta
authors.affiliation: Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Radiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Minami
authors.affiliation: Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kuni
authors.initials: K
authors.lastname: Ohtomo
authors.affiliation: Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans / Q000493:pharmacokinetics*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D058185:Magnetite Nanoparticles; D064847:Multimodal Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
keywords: hepatic tumor; magnetic resonance imaging; radiation-induced signal change; radiotherapy; superparamagnetic iron oxide