title: Prediction of chemotherapeutic response in bladder cancer using K-means clustering of dynamic contrast-enhanced (DCE)-MRI pharmacokinetic parameters.
abstract: OBJECTIVE
  To apply k-means clustering of two pharmacokinetic parameters derived from 3T dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the chemotherapeutic response in bladder cancer at the mid-cycle timepoint.
  
  
  METHODS
  With the predetermined number of three clusters, k-means clustering was performed on nondimensionalized Amp and kep estimates of each bladder tumor. Three cluster volume fractions (VFs) were calculated for each tumor at baseline and mid-cycle. The changes of three cluster VFs from baseline to mid-cycle were correlated with the tumor's chemotherapeutic response. Receiver-operating-characteristics curve analysis was used to evaluate the performance of each cluster VF change as a biomarker of chemotherapeutic response in bladder cancer.
  
  
  RESULTS
  The k-means clustering partitioned each bladder tumor into cluster 1 (low kep and low Amp), cluster 2 (low kep and high Amp), cluster 3 (high kep and low Amp). The changes of all three cluster VFs were found to be associated with bladder tumor response to chemotherapy. The VF change of cluster 2 presented with the highest area-under-the-curve value (0.96) and the highest sensitivity/specificity/accuracy (96%/100%/97%) with a selected cutoff value.
  
  
  CONCLUSIONS
  The k-means clustering of the two DCE-MRI pharmacokinetic parameters can characterize the complex microcirculatory changes within a bladder tumor to enable early prediction of the tumor's chemotherapeutic response.
authors.affiliation: Wright Center of Innovation in Biomedical Imaging, Department of Radiology, Ohio State University, Columbus, Ohio, USA.
authors.forename: Huyen T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
authors.forename: Zarine K
authors.initials: ZK
authors.lastname: Shah
authors.forename: Kamal
authors.initials: K
authors.lastname: Pohar
authors.forename: Amir
authors.initials: A
authors.lastname: Mortazavi
authors.forename: Debra L
authors.initials: DL
authors.lastname: Zynger
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Yang
authors.forename: Daniel
authors.initials: D
authors.lastname: Clark
authors.forename: Michael V
authors.initials: MV
authors.lastname: Knopp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use*; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D017063:Outcome Assessment, Health Care / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D019786:Gadolinium DTPA; D002945:Cisplatin
keywords: bladder cancer; chemotherapeutic response; k-means clustering; pharmacokinetic parameters