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Tissue Eng Part C Methods. 2018 Aug;24(8):465-473. doi: 10.1089/ten.TEC.2018.0144. Epub 2018 Jul 31.

Magnetic Resonance Imaging of Shear Stress and Wall Thickness in Tissue-Engineered Vascular Grafts.

Author information

1
1 Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
2
2 Center for Regenerative Medicine, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio.
3
3 Department of Surgery, Yale University School of Medicine , New Haven, Connecticut.
4
4 Department of Radiology & Biomedical Imaging, Yale University School of Medicine , New Haven, Connecticut.
5
5 Department of Biomedical Engineering, Yale University , New Haven, Connecticut.

Abstract

OBJECTIVES:

Tissue-engineered vascular grafts (TEVGs) have demonstrated potential for treating congenital heart disease (CHD); however, quantitative imaging for tracking functional and structural remodeling of TEVGs has not been applied. Therefore, we evaluated the potential of magnetic resonance (MR) imaging for assessing TEVG wall shear stress (WSS) and wall thickness in a large animal model.

METHODS:

Cell-seeded (n = 3) or unseeded (n = 3) TEVGs were implanted as inferior vena cava interposition grafts in juvenile lambs. Six months following implantation, two-dimensional phase-contrast MR imaging was performed at 3 slice locations (proximal, middle, and distal) to assess normalized WSS (i.e., WSS-to-cross sectional area). T2-weighted MR imaging was performed to assess TEVG wall thickness. Histology was qualitatively assessed, whereas immunohistochemistry was semiquantitatively assessed for smooth muscle cells (αSMA), macrophage lineage cells (CD11b), and matrix metalloproteinase activity (MMP-2 and MMP-9). Picrosirius Red staining was performed to quantify collagen content.

RESULTS:

TEVG wall thickness was significantly higher for proximal, middle, and distal slices in unseeded versus cell-seeded grafts. Significantly higher WSS values existed for proximal versus distal slice locations for cell-seeded TEVGs, whereas no differences in WSS existed between slices for unseeded TEVGs. Additionally, no differences in WSS existed between cell-seeded and unseeded groups. Both groups demonstrated elastin formation, without vascular calcification. Unseeded TEVGs possessed greater content of smooth muscle cells when compared with cell-seeded TEVGs. No differences in macrophage, MMP activity, or collagen content existed between groups.

CONCLUSION:

MR imaging allows for in vivo assessment of functional and anatomical characteristics of TEVGs and may provide a nonionizing approach that is clinically translatable to children undergoing treatment for CHD.

KEYWORDS:

congenital heart disease; magnetic resonance imaging; stem cells; tissue-engineered vascular grafts

PMID:
29978768
PMCID:
PMC6088254
[Available on 2019-08-01]
DOI:
10.1089/ten.TEC.2018.0144
[Indexed for MEDLINE]

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