title: Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.
abstract: OBJECTIVE
  The acquisition of ever increasing volumes of high resolution magnetic resonance imaging (MRI) data has created an urgent need to develop automated and objective image analysis algorithms that can assist in determining tumor margins, diagnosing tumor stage, and detecting treatment response.
  
  
  METHODS
  We have shown previously that Minkowski functionals, which are precise morphological and structural descriptors of image heterogeneity, can be used to enhance the detection, in T1 -weighted images, of a targeted Gd(3+) -chelate-based contrast agent for detecting tumor cell death. We have used Minkowski functionals here to characterize heterogeneity in T2 -weighted images acquired before and after drug treatment, and obtained without contrast agent administration.
  
  
  RESULTS
  We show that Minkowski functionals can be used to characterize the changes in image heterogeneity that accompany treatment of tumors with a vascular disrupting agent, combretastatin A4-phosphate, and with a cytotoxic drug, etoposide.
  
  
  CONCLUSIONS
  Parameterizing changes in the heterogeneity of T2 -weighted images can be used to detect early responses of tumors to drug treatment, even when there is no change in tumor size. The approach provides a quantitative and therefore objective assessment of treatment response that could be used with other types of MR image and also with other imaging modalities.
authors: Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK; Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
authors: Timothy J
authors: TJ
authors: Larkin
authors: Holly C
authors: HC
authors: Canuto
authors: Mikko I
authors: MI
authors: Kettunen
authors: Thomas C
authors: TC
authors: Booth
authors: De-En
authors: DE
authors: Hu
authors: Anant S
authors: AS
authors: Krishnan
authors: Sarah E
authors: SE
authors: Bohndiek
authors: André A
authors: AA
authors: Neves
authors: Charles
authors: C
authors: McLachlan
authors: Michael P
authors: MP
authors: Hobson
authors: Kevin M
authors: KM
authors: Brindle
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013267:Stilbenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013267:Stilbenes; D005047:Etoposide; C058728:fosbretabulin
keywords: Minkowski functionals; heterogeneity; image analysis; tumor