title: Dual-energy micro-computed tomography imaging of radiation-induced vascular changes in primary mouse sarcomas.
abstract: OBJECTIVE
  To evaluate the effects of radiation therapy on primary tumor vasculature using dual-energy (DE) micro-computed tomography (micro-CT).
  
  
  METHODS
  Primary sarcomas were generated with mutant Kras and p53. Unirradiated tumors were compared with tumors irradiated with 20 Gy. A liposomal-iodinated contrast agent was administered 1 day after treatment, and mice were imaged immediately after injection (day 1) and 3 days later (day 4) with DE micro-CT. CT-derived tumor sizes were used to assess tumor growth. After DE decomposition, iodine maps were used to assess tumor fractional blood volume (FBV) at day 1 and tumor vascular permeability at day 4. For comparison, tumor vascularity and vascular permeability were also evaluated histologically by use of CD31 immunofluorescence and fluorescently-labeled dextrans.
  
  
  RESULTS
  Radiation treatment significantly decreased tumor growth from day 1 to day 4 (P<.05). There was a positive correlation between CT measurement of tumor FBV on day 1 and extravasated iodine on day 4 with microvascular density (MVD) on day 4 (R(2)=0.53) and dextran accumulation (R(2)=0.63) on day 4, respectively. Despite no change in MVD measured by histology, tumor FBV significantly increased after irradiation as measured by DE micro-CT (0.070 vs 0.091, P<.05). Both dextran and liposomal-iodine accumulation in tumors increased significantly after irradiation, with dextran fractional area increasing 5.2-fold and liposomal-iodine concentration increasing 4.0-fold.
  
  
  CONCLUSIONS
  DE micro-CT is an effective tool for noninvasive assessment of vascular changes in primary tumors. Tumor blood volume and vascular permeability increased after a single therapeutic dose of radiation treatment.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Everett J
authors.initials: EJ
authors.lastname: Moding
authors.forename: Darin P
authors.initials: DP
authors.lastname: Clark
authors.forename: Yi
authors.initials: Y
authors.lastname: Qi
authors.forename: Yifan
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Ketan
authors.initials: K
authors.lastname: Ghaghada
authors.forename: G Allan
authors.initials: GA
authors.lastname: Johnson
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: Cristian T
authors.initials: CT
authors.lastname: Badea
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000502:physiology / Q000528:radiation effects*; D002199:Capillary Permeability / Q000502:physiology / Q000528:radiation effects*; D003287:Contrast Media; D005455:Fluorescent Antibody Technique / Q000379:methods; D007455:Iodine; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage; D055420:Perfusion Imaging / Q000379:methods; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011829:Radiation Dosage; D012509:Sarcoma / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D047368:Tumor Burden; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003287:Contrast Media; D008081:Liposomes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D007455:Iodine