title: Diffusion-weighted MRI for early detection and characterization of prostate cancer in the transgenic adenocarcinoma of the mouse prostate model.
abstract: OBJECTIVE
  To improve early diagnosis of prostate cancer to aid clinical decision-making. Diffusion-weighted magnetic resonance imaging (DW-MRI) is sensitive to water diffusion throughout tissues, which correlates with Gleason score, a histological measure of prostate cancer aggressiveness. In this study the ability of DW-MRI to detect prostate cancer onset and development was evaluated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.
  
  
  METHODS
  T2 -weighted and DW-MRI were acquired using a 7T MR scanner, 200 mm bore diameter; 10 TRAMP and 6 C57BL/6 control mice were scanned every 4 weeks from 8 weeks of age until sacrifice at 28-30 weeks. After sacrifice, the genitourinary tract was excised and sectioned for histological analysis. Histology slides registered with DW-MR images allowed for validation of DW-MR images and the apparent diffusion coefficient (ADC) as tools for cancer detection and disease stratification. An automated early assessment tool based on ADC threshold values was developed to aid cancer detection and progression monitoring.
  
  
  RESULTS
  The ADC differentiated between control prostate ((1.86 ± 0.20) × 10(-3) mm(2) /s) and normal TRAMP prostate ((1.38 ± 0.10) × 10(-3) mm(2) /s) (P = 0.0001), between TRAMP prostate and well-differentiated cancer ((0.93 ± 0.18) × 10(-3) mm(2) /s) (P = 0.0006), and between well-differentiated cancer and poorly differentiated cancer ((0.63 ± 0.06) × 10(-3) mm(2) /s) (P = 0.02).
  
  
  CONCLUSIONS
  DW-MRI is a tool for early detection of cancer, and discrimination between cancer stages in the TRAMP model. The incorporation of DW-MRI-based prostate cancer stratification and monitoring could increase the accuracy of preclinical trials using TRAMP mice.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.|St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Hill
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.|St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.|St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Teruel
authors.affiliation: Division of Radiotherapy and Imaging, Institute of Cancer Research and Royal Marsden NHS Trust, London, UK.
authors.forename: Yann
authors.initials: Y
authors.lastname: Jamin
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Widerøe
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Søgaard
authors.affiliation: Department of Pathology, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Størkersen
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Rodrigues
authors.affiliation: Centre for Evolution and Cancer, Institute of Cancer Research, London, UK.|Centre for Molecular Pathology, Royal Marsden Hospital, London, UK.|Division of Molecular Pathology, Institute of Cancer Research, London, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heindl
authors.affiliation: Centre for Evolution and Cancer, Institute of Cancer Research, London, UK.|Centre for Molecular Pathology, Royal Marsden Hospital, London, UK.|Division of Molecular Pathology, Institute of Cancer Research, London, UK.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.|St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Siver A
authors.initials: SA
authors.lastname: Moestue
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology; D000818:Animals; D001331:Automation; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010363:Pattern Recognition, Automated; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: ADC; cancer detection; diffusion weighted MRI; prostate cancer; transgenic adenocarcinoma of the mouse prostate