title: Quantitative probabilistic functional diffusion mapping in newly diagnosed glioblastoma treated with radiochemotherapy.
abstract: BACKGROUND
  Functional diffusion mapping (fDM) is a cancer imaging technique that uses voxel-wise changes in apparent diffusion coefficients (ADC) to evaluate response to treatment. Despite promising initial results, uncertainty in image registration remains the largest barrier to widespread clinical application. The current study introduces a probabilistic approach to fDM quantification to overcome some of these limitations.
  
  
  METHODS
  A total of 143 patients with newly diagnosed glioblastoma who were undergoing standard radiochemotherapy were enrolled in this retrospective study. Traditional and probabilistic fDMs were calculated using ADC maps acquired before and after therapy. Probabilistic fDMs were calculated by applying random, finite translational, and rotational perturbations to both pre-and posttherapy ADC maps, then repeating calculation of fDMs reflecting changes after treatment, resulting in probabilistic fDMs showing the voxel-wise probability of fDM classification. Probabilistic fDMs were then compared with traditional fDMs in their ability to predict progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Probabilistic fDMs applied to patients with newly diagnosed glioblastoma treated with radiochemotherapy demonstrated shortened PFS and OS among patients with a large volume of tumor with decreasing ADC evaluated at the posttreatment time with respect to the baseline scans. Alternatively, patients with a large volume of tumor with increasing ADC evaluated at the posttreatment time with respect to baseline scans were more likely to progress later and live longer. Probabilistic fDMs performed better than traditional fDMs at predicting 12-month PFS and 24-month OS with use of receiver-operator characteristic analysis. Univariate log-rank analysis on Kaplan-Meier data also revealed that probabilistic fDMs could better separate patients on the basis of PFS and OS, compared with traditional fDMs.
  
  
  CONCLUSIONS
  Results suggest that probabilistic fDMs are a more predictive biomarker in terms of 12-month PFS and 24-month OS in newly diagnosed glioblastoma, compared with traditional fDM analysis.
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 924 Westwood Blvd., Ste. 615, Los Angeles, CA 90024, USA. bellingson@mednet.ucla.edu
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Albert
authors.initials: A
authors.lastname: Lai
authors.forename: Phioanh L
authors.initials: PL
authors.lastname: Nghiemphu
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liau
authors.forename: Whitney B
authors.initials: WB
authors.lastname: Pope
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D038524:Diffusion Magnetic Resonance Imaging; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide