title: Diffusion-weighted MR imaging of metastatic abdominal and pelvic tumours is sensitive to early changes induced by a VEGF inhibitor using alternative diffusion attenuation models.
abstract: OBJECTIVE
  To assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor.
  
  
  METHODS
  Twenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed.
  
  
  RESULTS
  Diffusion coefficient repeatabilities from all models were < 6%; f and D* (bi-exponential) were 22% and 44%; α (stretched-exponential) was 4.2%. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed.
  
  
  CONCLUSIONS
  DW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes.
  
  
  CONCLUSIONS
  • Non-mono-exponential diffusion models widen sensitivity to a broader class of tissue properties. • A stretched-exponential model robustly detects changes after 7 days of VEGF-inhibitor treatment. • There are very weak correlations between DWI-IVIM perfusion and similar DCE-MRI measures. • Diffusion-weighted MRI is a highly informative technique for assessing novel tumour therapies.
authors.affiliation: CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK. matthew.orton@icr.ac.uk.|Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 5MG, UK. matthew.orton@icr.ac.uk.
authors.forename: Matthew R
authors.identifier: http://orcid.org/0000-0002-0805-763X
authors.initials: MR
authors.lastname: Orton
authors.affiliation: CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.|Department of Radiology, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Messiou
authors.affiliation: CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: David
authors.initials: D
authors.lastname: Collins
authors.affiliation: Department of Radiology, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Morgan
authors.affiliation: Early Clinical Development, AstraZeneca, Macclesfield, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Tessier
authors.affiliation: Early Clinical Development, AstraZeneca, Macclesfield, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Young
authors.affiliation: CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.|Department of Radiology, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: Nandita
authors.initials: N
authors.lastname: deSouza
authors.affiliation: CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
mesh_terms: D000008:Abdominal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D008962:Models, Theoretical; D010386:Pelvic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D011799:Quinazolines / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D055815:Young Adult; D007211:Indoles
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C500926:cediranib; D007211:Indoles
keywords: Analysis, regression; Cancer; Diffusion magnetic resonance imaging; Magnetic resonance imaging, functional; Vascular endothelial growth factor