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Farhat Lab
Farhat Lab

Magnetic resonance imaging

The overall objective of this proposal is to develop a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) approach based on different sizes of contrast agents for quantifying microvascular properties in tissue-engineered bladder constructs enhanced with vessel-inducing growth factors.

Tissue engineering is a promising new treatment option to restore or enhance function in damaged or diseased organs, especially in patients where traditional transplantation or artificial replacement is not viable. However, a current challenge in tissue engineering, particularly in the case of large organs, is how to rapidly supply blood to the engineered construct to prevent fibrosis. Strategies to achieve immediate blood vessel growth are, therefore, critical to overall success. One strategy, the incorporation of vessel-inducing growth factors, such as VEGF, has demonstrated vascularization of an initially avascular graft. The ideal vascular density for proper bladder regeneration is, however, unknown, as are the optimal dosage, timing, and frequency of VEGF incorporation. Furthermore, given the complexity of angiogenesis, administration of additional growth factors may be needed to generate a well-tempered and sustained neovasculature for normal tissue function. Development of angiogenic strategies is currently hampered by lack of a reliable, non-invasive monitoring tool to assess angiogenic development in a serial fashion.

In this proposal, we develop a DCE-MRI approach for non-invasively quantifying microvascular properties in rabbit bladder constructs enhanced with VEGF. Preliminary work has demonstrated the feasibility of standard DCE-MRI in distinguishing constructs with vastly different vascularization. Distinction of more subtle vascular differences is desired, as is independent measurement of properties such as blood volume, permeability, and cellular fraction, which is not feasible with standard DCE-MRI techniques. Also, contrast agents of different sizes are likely needed to achieve sensitivity to the spectrum of microvascular properties that are anticipated in constructs prepared with varying VEGF levels and at different stages of vessel growth and maturation. Briefly, the aims are to:

  1. investigate MR contrast agents of different molecular weights for microvascular measurements in grafts at various degrees and stages of vascularization
  2. optimize DCE-MRI acquisition and analysis techniques, using a contrast agent(s) appropriate for the indicated time-point and anticipated microvessel growth, to ensure accurate and independent microvascular measurements
  3. investigate and optimize determinants necessary for regenerating functionally normal bladder tissue, using the proposed DCE-MRI approach to monitor neovascularization in a non-invasive and serial fashion

All DCE-MRI measurement will be correlated to histology.

The long-term goal of this research is to accelerate and improve our understanding of the mechanisms by which neovascularization can be established and maintained in engineered bladder tissue, with the ultimate goal of creating a successful bladder substitute.