title: Free Form Deformation-Based Image Registration Improves Accuracy of Traction Force Microscopy.
abstract: Traction Force Microscopy (TFM) is a widespread method used to recover cellular tractions from the deformation that they cause in their surrounding substrate. Particle Image Velocimetry (PIV) is commonly used to quantify the substrate's deformations, due to its simplicity and efficiency. However, PIV relies on a block-matching scheme that easily underestimates the deformations. This is especially relevant in the case of large, locally non-uniform deformations as those usually found in the vicinity of a cell's adhesions to the substrate. To overcome these limitations, we formulate the calculation of the deformation of the substrate in TFM as a non-rigid image registration process that warps the image of the unstressed material to match the image of the stressed one. In particular, we propose to use a B-spline -based Free Form Deformation (FFD) algorithm that uses a connected deformable mesh to model a wide range of flexible deformations caused by cellular tractions. Our FFD approach is validated in 3D fields using synthetic (simulated) data as well as with experimental data obtained using isolated endothelial cells lying on a deformable, polyacrylamide substrate. Our results show that FFD outperforms PIV providing a deformation field that allows a better recovery of the magnitude and orientation of tractions. Together, these results demonstrate the added value of the FFD algorithm for improving the accuracy of traction recovery.
authors.affiliation: Biomechanics Section, Department of Mechanical Engineering, KU Leuven, 3001, Leuven, Belgium.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Jorge-Peñas
authors.affiliation: Biomechanics Section, Department of Mechanical Engineering, KU Leuven, 3001, Leuven, Belgium.
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo-Alvarez
authors.affiliation: Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, School of Medicine, 28006, Madrid, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Aguilar-Cuenca
authors.affiliation: Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, School of Medicine, 28006, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vicente-Manzanares
authors.affiliation: Multiscale in Mechanical and Biological Engineering (M2BE), Department of Mechanical Engineering, Aragon Institute of Engineering Research (I3A), University of Zaragoza, 50018, Zaragoza, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Garcia-Aznar
authors.affiliation: Biomechanics Section, Department of Mechanical Engineering, KU Leuven, 3001, Leuven, Belgium.|Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Van Oosterwyck
authors.affiliation: Regenerative Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, 4059, Brisbane, Australia.
authors.forename: Elena M
authors.initials: EM
authors.lastname: de-Juan-Pardo
authors.affiliation: Cancer Imaging Laboratory, Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Navarra's Health Research Institute (IDISNA), 31008, Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz-de-Solorzano
authors.affiliation: Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid, Instituto de Investigación Sanitaria Gregorio Marañon, 28911, Madrid, Spain.
authors.forename: Arrate
authors.initials: A
authors.lastname: Muñoz-Barrutia
mesh_terms: D021621:Imaging, Three-Dimensional / Q000379:methods*; D018625:Microscopy, Atomic Force / Q000379:methods*; D008962:Models, Theoretical