Optical coherence elastography (with photonic or ultrasound forces)

Biophysical interactions between cell and extracellular matrix (ECM) play an important role in biological processes, including initiation and progression of cancer, stem cell differentiation, morphogenesis, and wound healing. Importantly, cell-ECM interactions have been shown to differ in 2D versus 3D environment, driving the pursuit of cellular-scale studies in the more physiologically relevant 3D engineered cellular systems and biological tissues. However, existing approaches for characterizing ECM mechanical properties are typically limited to bulk mechanical testing or atomic force microscopy (which only probes the 2D surface of the sample). Optical coherence elastography (OCE) can enable high-resolution mechanical characterization of biological samples. It works by combining mechanical loading (‘palpation’) of the sample with ultraprecise OCT imaging of the resulting sample deformations, followed by mathematical reconstruction of mechanical properties from the measured deformation map. Our lab has developed optical elastography techniques based on highly-localized mechanical excitation provided by photonic and acoustic forces, and ultra-precise displacement detection by phase-sensitive OCT.

For cellular-scale mechanical microscopy of 3D engineered ECM, photonic force optical coherence elastography (PF-OCE) utilizes force from a weakly-focused laser beam to provide localized mechanical excitation on micro-beads embedded in the samples. Local mechanical properties of the ECM around each embedded bead is reconstructed from the measured bead mechanical responses. For volumetric mechanical characterization of biological tissues, acoustic radiation force optical coherence elastography (ARF-OCE) utilizes force from a focused ultrasound beam to provide localized mechanical excitation on ex vivo tissue specimens or in vivo animal models. Local strain and tissue mechanical properties are reconstructed from the measured tissue deformations.

3D mechanical microscopy of side-by-side agarose hydrogel with PF-OCE. PF-OCE utilizes photonic force from a weakly-focused laser beam to locally “push” on individual micro-beads embedded in the 3D viscoelastic medium. The force-mediated bead “mechanical response” (i.e., bead motion) is interferometrically detected by phase-sensitive OCT, after compensating for the confounding absorption-mediated “photothermal response” of the medium. A larger bead mechanical response implies a more compliant “microenvironment” around that particular bead. Adapted from Leartprapun et al., Nat. Commun., 2018.

See our poster on PF-OCE and ARF-OCE here.

Relevant publications

OCE review paper

  1. Mulligan J.A.†, Untracht G.R.†, Chandrasekaran S.N., Brown C.N., and Adie S.G., “Emerging approaches for high-resolution imaging of tissue biomechanics with optical coherence elastography”, IEEE Journal of Selected Topics in Quantum Electronics, 22(3):6800520, 2016.

PF-OCE papers & conference presentations

  1. Lin, Y., Leartprapun, N., Luo, J., Adie, S.G., “Characterizing three-dimensional micromechanical heterogeneities of the extracellular matrix with photonic-force optical coherence elastography“, SPIE Proc., Vol. 11645, Optical Elastography and Tissue Biomechanics VIII; 1164505, 2021.
  2. Lin, Y., Leartprapun, N., Adie, S.G., “Spectroscopic photonic force optical coherence elastography”, Opt. Lett.  44, 4897-4900, 2019.
  3. Leartprapun, N., Lin, Y., Adie, S.G., “Microrheological quantification of viscoelastic properties with photonic force optical coherence elastography”, Opt. Express, 27, 22615-22630, 2019.
  4. Leartprapun, N., Iyer, R.R., Untracht, G.R. et al., “Photonic force optical coherence elastography for three-dimensional mechanical microscopy”, Nature Communications, 9, 2079, 2018.
  5. Leartprapun, N., Iyer, R.R., Adie, S.G. “Depth-resolved measurement of optical radiation-pressure forces with optical coherence tomography”, Opt. Express, 26, 2410-2426, 2018.

ARF-OCE papers

  1. Leartprapun, N., Iyer, R.R., Mackey, C.D., Adie, S.G. “Spatial localization of mechanical excitation affects spatial resolution, contrast, and contrast-to-noise ratio in acoustic radiation force optical coherence elastography”, Biomed. Opt. Express, 10, 5877-5904, 2019.
  2. Leartprapun, N., Iyer, R.R., Adie, S.G. “Model-independent quantification of soft tissue viscoelasticity with dynamic optical coherence elastography,” Proc. SPIE, 10053, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXI, 1005322, 2017.