title: CT perfusion imaging as an early biomarker of differential response to stereotactic radiosurgery in C6 rat gliomas.
abstract: BACKGROUND
  The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model.
  
  
  METHODS
  Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival >15 days were designated as responders while those with survival ≤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline.
  
  
  RESULTS
  Early signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P<0.04). Responders to stereotactic radiosurgery showed lower relative blood volume (rBV), and permeability-surface area (PS) product on day 7 post-stereotactic radiosurgery when compared to controls and non-responders (P<0.05). rBV and PS on day 7 showed correlations with overall survival (P<0.05), and were predictive of survival with 92% accuracy.
  
  
  CONCLUSIONS
  Response to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation.
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada; London Regional Cancer Program, London, Ontario, Canada.
authors.forename: Timothy Pok Chi
authors.initials: TP
authors.lastname: Yeung
authors.affiliation: Department of Pathology, Western University, London, Ontario, Canada; Department of Pathology, King Abdulaziz University, Jeddah, Makkah, Saudi Arabia.
authors.forename: Maher
authors.initials: M
authors.lastname: Kurdi
authors.affiliation: Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.
authors.forename: Baraa
authors.initials: B
authors.lastname: Al-Khazraji
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; Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada; Lawson Imaging, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hoffman
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, Canada.
authors.forename: Dwayne
authors.initials: D
authors.lastname: Jackson
authors.affiliation: Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Cathie
authors.initials: C
authors.lastname: Crukley
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: 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; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000601:surgery*; D005910:Glioma / Q000000981:diagnostic imaging / Q000601:surgery*; D008297:Male; D055420:Perfusion Imaging; D011832:Radiation Injuries / Q000000981:diagnostic imaging / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D014055:Tomography, Emission-Computed