title: Noninvasive monitoring of microvascular changes with partial irradiation using dynamic contrast-enhanced and blood oxygen level-dependent magnetic resonance imaging.
abstract: OBJECTIVE
  The microvasculature of a tumor plays an important role in its response to radiation therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and blood oxygen level-dependent (BOLD) MRI are both sensitive to vascular characteristics. The present study proposed a partial irradiation approach to a xenograft tumor to investigate the intratumoral response to radiation therapy using DCE and BOLD MRI.
  
  
  METHODS
  TRAMP-C1 tumors were grown in C57BL/6J mice. Partial irradiation was performed on the distal half of the tumor with a single dose of 15 Gy. DCE MRI was performed to derive the endothelium transfer constant, K(trans), using pharmacokinetic analysis. BOLD MRI was performed using quantitative R2 measurements with carbogen breathing. The histology of the tumor was analyzed using hematoxylin and eosin staining and CD31 staining to detect endothelial cells. The differences between the irradiated and nonirradiated regions of the tumor were assessed using K(trans) values, ΔR2 values in response to carbogen and microvascular density (MVD) measurements.
  
  
  RESULTS
  A significantly increased K(trans) and reduced BOLD response to carbogen were found in the irradiated region of the tumor compared with the nonirradiated region (P<.05). Histologic analysis showed a significant aggregation of giant cells and a reduced MVD in the irradiated region of the tumor. The radiation-induced difference in the BOLD response was associated with differences in MVD and K(trans).
  
  
  CONCLUSIONS
  We demonstrated that DCE MRI and carbogen-challenge BOLD MRI can detect differential responses within a tumor that may potentially serve as noninvasive imaging biomarkers to detect microvascular changes in response to radiation therapy.
authors.affiliation: Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Jiun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Hong
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Lin
authors.forename: Chung-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: Yau-Yau
authors.initials: YY
authors.lastname: Wai
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Ng
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Wu
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D003287:Contrast Media; D015726:Giant Cells / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects*; D009374:Neoplasms, Experimental / Q000097:blood / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D010100:Oxygen / Q000097:blood* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D014183:Transplantation, Heterologous
chemical_list: D003287:Contrast Media; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen