title: Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia.
abstract: BACKGROUND
  Tumor hypoxia is associated with treatment resistance to cancer therapies. Hypoxia can be investigated by immunohistopathologic methods but such procedure is invasive. A non-invasive method to interrogate tumor hypoxia is an attractive option as such method can provide information before, during, and after treatment for personalized therapies. Our study evaluated the correlations between computed tomography (CT) perfusion parameters and immunohistopathologic measurement of tumor hypoxia.
  
  
  METHODS
  Wistar rats, 18 controls and 19 treated with stereotactic radiosurgery (SRS), implanted with the C6 glioma tumor were imaged using CT perfusion on average every five days to monitor tumor growth. A final CT perfusion scan and the brain were obtained on average 14 days (8-22 days) after tumor implantation. Tumor hypoxia was detected immunohistopathologically with pimonidazole. The tumor, necrotic, and pimonidazole-positive areas on histology samples were measured. Percent necrotic area and percent hypoxic areas were calculated. Tumor volume (TV), blood flow (BF), blood volume (BV), and permeability-surface area product (PS) were obtained from the CT perfusion studies. Correlations between CT perfusion parameters and histological parameters were assessed by Spearman's ρ correlation. A Bonferroni-corrected P value < 0.05 was considered significant.
  
  
  RESULTS
  BF and BV showed significant correlations with percent hypoxic area ρ = -0.88, P < 0.001 and ρ = -0.81, P < 0.001, respectively, for control animals and ρ = -0.7, P < 0.001 and ρ = -0.6, P = 0.003, respectively, for all animals, while TV and BV were correlated (ρ = -0.64, P = 0.01 and ρ = -0.43, P = 0.043, respectively) with percent necrotic area. PS was not correlated with either percent necrotic or percent hypoxic areas.
  
  
  CONCLUSIONS
  Percent hypoxic area provided significant correlations with BF and BV, suggesting that CT perfusion parameters are potential non-invasive imaging biomarkers of tumor hypoxia.
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.|Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Timothy Pok Chi
authors.initials: TP
authors.lastname: Yeung
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.|Robarts Research Institute, Western University, London, Ontario, Canada.|Lawson Imaging, Lawson Health Research Institute, London, Ontario, Canada.|Department of Medical Imaging, Western University, London, Ontario, Canada.|Department of Oncology, Western University, London, Ontario, Canada.
authors.forename: Ting-Yim
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.|Department of Oncology, Western University, London, Ontario, Canada.|London Regional Cancer Program, London, Ontario, Canada.
authors.forename: Glenn
authors.initials: G
authors.lastname: Bauman
authors.affiliation: Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Cathie
authors.initials: C
authors.lastname: Crukley
authors.affiliation: Lawson Imaging, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Morrison
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.|Lawson Imaging, Lawson Health Research Institute, London, Ontario, Canada.|Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hoffman
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.|Department of Oncology, Western University, London, Ontario, Canada.|London Regional Cancer Program, London, Ontario, Canada.
authors.forename: Slav
authors.initials: S
authors.lastname: Yartsev
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000150:complications* / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000098:blood supply* / Q000150:complications* / Q000473:pathology; D000860:Hypoxia / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D055420:Perfusion Imaging; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers