Ultrahigh-field DCE-MRI of angiogenesis in a novel angiogenesis mouse model.
OBJECTIVE
To be able to screen and identify potential candidate agents for noninvasive imaging of diseases involving angiogenesis, a standardized in vivo angiogenesis model is needed. Angiogenesis is a common feature of many pathological conditions and has become an important target for diagnosis and treatment, with many noninvasive imaging agents emerging.


METHODS
Uniform scaffolds consisting of porous and flexible polycaprolactone were implanted subcutaneously in mice and studied after 1 to 6 weeks to describe the time course of angiogenesis. The model was characterized by histology and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).


RESULTS
Microscopic examination revealed progressive ingrowth of new vessels from the periphery, leading to a fully vascularized scaffold within 6 weeks. Blood flow through the new vessels, assessed by DCE-MRI, revealed peripheral vascularization corresponding to 12.3% (SD 6.1%) of scaffold area at week 1 and a more uniform and complete distribution of vessels corresponding to 84.1% (SD 16.2%) of scaffold area at week 4.


CONCLUSIONS
In agreement with microscopic examination, noninvasive DCE-MRI visualized progressive development of new vessels in a novel and standardized murine angiogenesis model, making this model suitable for screening angiogenesis-related drugs and contrast agents.
Atherosclerosis Research Unit, Institute of Clinical Medicine and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Wittenborn@oncology.dk
Thomas
T
Wittenborn
Thomas
T
Nielsen
Jens V
JV
Nygaard
Esben K U
EK
Larsen
Troels
T
Thim
Louise M
LM
Rydtoft
Thomas
T
Vorup-Jensen
Jørgen
J
Kjems
Niels Chr
NC
Nielsen
Michael R
MR
Horsman
Erling
E
Falk
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D018450:Disease Progression; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011091:Polyesters; D016062:Porosity; D054457:Tissue Scaffolds
D003287:Contrast Media; D011091:Polyesters; C016240:polycaprolactone; D019786:Gadolinium DTPA