title: In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model.
abstract: BACKGROUND
  Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability.
  
  
  METHODS
  6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.
  
  
  RESULTS
  MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm3+/-243 mm3) with MRI (mean 918 mm3+/-193 mm3) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.
  
  
  CONCLUSIONS
  This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, Ernst-Moritz-Arndt-University, Friedrich-Loeffler-Str. 23 b, Greifswald, Germany.
authors.forename: Ivo L
authors.initials: IL
authors.lastname: Partecke
authors.forename: André
authors.initials: A
authors.lastname: Kaeding
authors.forename: Matthias
authors.initials: M
authors.lastname: Sendler
authors.forename: Nele
authors.initials: N
authors.lastname: Albers
authors.forename: Jens-P
authors.initials: JP
authors.lastname: Kühn
authors.forename: Sven
authors.initials: S
authors.lastname: Speerforck
authors.forename: Sebastian
authors.initials: S
authors.lastname: Roese
authors.forename: Florian
authors.initials: F
authors.lastname: Seubert
authors.forename: Stephan
authors.initials: S
authors.lastname: Diedrich
authors.forename: Sandra
authors.initials: S
authors.lastname: Kuehn
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Weiss
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
authors.forename: Stefan
authors.initials: S
authors.lastname: Hadlich
authors.forename: Norbert
authors.initials: N
authors.lastname: Hosten
authors.forename: Claus-D
authors.initials: CD
authors.lastname: Heidecke
authors.forename: Ralf
authors.initials: R
authors.lastname: Puls
authors.forename: Wolfram
authors.initials: W
authors.lastname: von Bernstorff
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D011859:Radiography; D012039:Regional Blood Flow