title: Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.
abstract: OBJECTIVE
  To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder.
  
  
  METHODS
  Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test.
  
  
  RESULTS
  Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening.
  
  
  CONCLUSIONS
  The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer.
  
  
  CONCLUSIONS
  • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.
authors.affiliation: Wright Center of Innovation in Biomedical Imaging, Department of Radiology, The Ohio State University, 395 W. 12th Ave., Room 430, Columbus, OH, 43210, USA.
authors.forename: Huyen T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Wright Center of Innovation in Biomedical Imaging, Department of Radiology, The Ohio State University, 395 W. 12th Ave., Room 430, Columbus, OH, 43210, USA.
authors.forename: Zarine K
authors.initials: ZK
authors.lastname: Shah
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Mortazavi
authors.affiliation: Department of Urology, The Ohio State University, Columbus, OH, USA.
authors.forename: Kamal S
authors.initials: KS
authors.lastname: Pohar
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, USA.|Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Zynger
authors.affiliation: Wright Center of Innovation in Biomedical Imaging, Department of Radiology, The Ohio State University, 395 W. 12th Ave., Room 430, Columbus, OH, 43210, USA. knopp.16@osu.edu.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Knopp
mesh_terms: D000368:Aged; D015653:Cystectomy; D003937:Diagnosis, Differential; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D001745:Urinary Bladder Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D014867:Water
chemical_list: D014867:Water
keywords: Apparent Diffusion Coefficient; Bladder malignancy; Histogram analysis; K-means clustering; Tumour heterogeneity