Ultrahigh‐field DCE‐MRI of angiogenesis in a novel angiogenesis mouse model

Abstract

Purpose: 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. Materials and 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 contrastenhanced 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. Conclusion: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.

Accumulation of nano-sized particles in a murine model of angiogenesis

“…Polycapro-lactone (PCL) discs were made in-house and prepared according to Andersen et al [23]. The procedure for implantation of porous PCL discs has been previously described [21]. In brief, a small incision (1.5 cm) was made in the skin on the back, through which the PCL discs (measuring 8mm in diameter and 2-3mm in height) were subcutaneously implanted.…”

“…Hydrodynamic size, zeta potential, and blood circulation half-life were estimated using standard methods, and its ability to localize to areas of angiogenesis was assessed by ultrahigh-field MRI in a recently described murine angiogenesis model [21]. …”

The Application of Nanotechnology for Implant Drug Release

“…Diffusion is distance limited and can typically only supply cells that are within 100 μm of a capillary. Neovascularization is promoted automatically when cells within a scaffold suffers from a lack of nutrient or oxygen [ 111 ], but may take place too slowly to prevent necrosis in large implants. Releasing drugs that promote vascularization from scaffolds has, therefore, received much attention in tissue engineering.…”

Multimodal Ultrasound-Photoacoustic Imaging of Tissue Engineering Scaffolds and Blood Oxygen Saturation In and Around the Scaffolds

“…27 Unlike CT that uses harmful x-ray radiation, MRI is considerably safer. 26,[29][30][31][32][33][34] However, the contrast of tissue engineering scaffolds monitored using MRI is poor until water can penetrate and perfuse the scaffold. [33][34][35] This method also requires the use of contrast agents with high relaxivity values.…”

“…[19][20][21] To this end, various superficial and whole-body small animal imaging modalities have recently been explored for imaging tissue engineering scaffolds. [22][23][24][25][26][27][28] Each modality has its advantages and limitations. Superficial optical imaging techniques, with excellent sub-mm resolutions, such as bioluminescence, fluorescence, optical coherence tomography (OCT), and two-photon imaging have various limitations such as low tissue penetration (tens to hundred of micrometers), optical scattering and attenuation, or interferences due to background tissue autofluorescence.…”