title: Magnetic resonance imaging-based tumour perfusion parameters are biomarkers predicting response after radiation to brain metastases.
abstract: OBJECTIVE
  To investigate whether early relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and permeability (Ktrans(2)) measurements may serve as magnetic resonance imaging (MRI) biomarkers of radiation response or progression for brain metastases.
  
  
  METHODS
  Seventy brain metastases in 44 patients treated with either stereotactic radiosurgery or whole brain radiotherapy were imaged with dynamic susceptibility and dynamic contrast enhancement MRI at baseline, 1 week and 1 month after treatment. The final response status was determined according to volume criteria derived from a 1 year post-treatment MRI or last available follow-up MRI. Tumours were characterised as responders, non-responders, progressors and non-progressors and compared for Ktrans(2), rCBF and rCBV differences. Uni- and multivariate analysis evaluated factors associated with tumour response and progression at 1 week and 1 month. A generalised estimating equations (GEE) model accounted for multiple tumours per subject. Receiver operator characteristic (ROC) analysis identified optimal cut-off values, sensitivity and specificity for response or progression.
  
  
  RESULTS
  Tumour responders showed lower Ktrans(2) and reduced rCBF at 1 week (P < 0.05 each). Progressive disease showed lower rCBF and reduced rCBV at 1 month (P < 0.05 each). GEE and multivariate analysis revealed lower Ktrans(2) at 1 week, an absence of prior radiation predicted response. At 1 month only lower rCBV predicted progressive disease on GEE and multivariate analysis. Optimal cut-off points for Ktrans(2) and rCBV were 1.37 and 2.03 with sensitivity and specificity of 61.5 and 81.1% and 73.9 and 81.8%, respectively.
  
  
  CONCLUSIONS
  Lower Ktrans(2) at 1 week and rCBV at 1 month discriminated responders and progressive disease, respectively.
authors.affiliation: Department of Medical Imaging, Division of Neuroradiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Department of Biomedical Physics, Ryerson University, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Jakubovic
authors.affiliation: Department of Radiation Oncology, Odette Cancer Centre of the Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Sahgal
authors.affiliation: Department of Radiation Oncology, Odette Cancer Centre of the Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Soliman
authors.affiliation: Department of Medical Imaging, Division of Neuroradiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Milwid
authors.affiliation: Department of Medical Imaging, Division of Neuroradiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Imaging, Division of Neuroradiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Eilaghi
authors.affiliation: Department of Medical Imaging, Division of Neuroradiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: richard.aviv@sunnybrook.ca.
authors.forename: R I
authors.initials: RI
authors.lastname: Aviv
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D001810:Blood Volume / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000098:blood supply / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D002560:Cerebrovascular Circulation / Q000528:radiation effects*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010477:Perfusion; D011379:Prognosis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects*; D011878:Radiotherapy / Q000009:adverse effects*
chemical_list: D015415:Biomarkers
keywords: Cancer; dynamic contrast-enhanced imaging; dynamic susceptibility imaging; magnetic resonance perfusion; magnetic resonance permeability; metastasis