title: Why prostate tumour delineation based on apparent diffusion coefficient is challenging: an exploration of the tissue microanatomy.
abstract: BACKGROUND
  Focal boosting of prostate tumours to improve outcome, requires accurate tumour delineation. For this, the apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging (DWI) seems a useful tool. On voxel level, the relationship between ADC and histological presence of tumour is, however, ambiguous. Therefore, in this study the relationship between ADC and histological variables was investigated on voxel level to understand the strengths and limitations of DWI for prostate tumour delineation.
  
  
  METHODS
  Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI exam and the ADC was calculated. From whole-mount histological sections cell density and glandular area were retrieved for every voxel. The distribution of all variables was described for tumour, peripheral zone (PZ) and central gland (CG) on regional and voxel level. Correlations between variables and differences between regions were calculated.
  
  
  RESULTS
  Large heterogeneity of ADC on voxel level was observed within tumours, between tumours and between patients. This heterogeneity was reflected by the distribution of cell density and glandular area. On regional level, tumour was different from PZ having higher cell density (p = 0.007), less glandular area (p = 0.017) and lower ADCs (p = 0.017). ADC was correlated with glandular area (r = 0.402) and tumour volume (r = -0.608), but not with Gleason score. ADC tended to decrease with increasing cell density (r = -0.327, p = 0.073). On voxel level, correlations between ADC and histological variables varied among patients, for cell density ranging from r = -0.439 to r = 0.261 and for glandular area from r = 0.593 to r = 0.207.
  
  
  CONCLUSIONS
  The variation in ADC can to a certain extent be explained by the variation in cell density and glandular area. The ADC is highly heterogeneous, which reflects the heterogeneity of malignant and benign prostate tissue. This heterogeneity might however obscure small tumours or parts of tumours. Therefore, DWI has to be used in the context of multiparametric MRI.
authors.affiliation: Department of Radiotherapy, University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Alie
authors.initials: A
authors.lastname: Borren
authors.forename: Maaike R
authors.initials: MR
authors.lastname: Moman
authors.forename: Greetje
authors.initials: G
authors.lastname: Groenendaal
authors.forename: Arto E
authors.initials: AE
authors.lastname: Boeken Kruger
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Petra
authors.initials: P
authors.lastname: van der Groep
authors.forename: Uulke A
authors.initials: UA
authors.lastname: van der Heide
authors.forename: Marco
authors.initials: M
authors.lastname: van Vulpen
authors.forename: Marielle E P
authors.initials: ME
authors.lastname: Philippens
mesh_terms: D000368:Aged; D002452:Cell Count; D038524:Diffusion Magnetic Resonance Imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000473:pathology* / Q000601:surgery; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D047368:Tumor Burden