Depth Resolved Quantitative Imaging of Tissue Ultra-Structure

Sub-diffusive Spatial Frequency Domain Imaging

Project #1: Spatial Frequency Resolved Characterization of Wound Healing

In this project, we seek to differentiate tissue scattering properties in thin layers (~50-100 micron) of skin tissue. This is critical to non-invasively quantify new cell growth (re-epithelialization) in wound healing. Our approach exploits the subtle differences in structured light propagation into tissue as a function of how fine the illumination pattern is.

Picture that shows results from the research.

This can be a vital tool to assess the efficacy of wound healing therapeutics as tissue scattering properties are sensitive to microscopic structure (e.g. collagen and cellular morphology). By non-invasively probing these properties over different tissue volumes, it is possible to volumetrically reconstruct tissue structures that the eye cannot perceive, like new cell growth, over centimeter fields of view. This can allow for the continual monitoring of wound healing progression with perturbing the tissue itself.

Graphics showing the results of the research.

Project #2: Spectral Depth Penetrance of Light Scattering: a New Approach to Melanoma Screening

We use quantitative spectroscopy to find a way to help clinical practitioners distinguish pigmented lesions by providing information inaccessible to the human eye. Our main goals are to develop a platform that allows early detection of melanoma (improved sensitivity) and reduces the number of unnecessary invasive biopsies (improved specificity).

Graphics showing how skin looks underneath.

Previous absorption-based, wide-field imaging approaches estimate the distribution thickness of melanin and the melanin concentration up to 100-200 micron in depth. Staging of melanoma, however, requires a technique that can reach depths of 1-4 mm. Therefore, a scattering based technique used in this project is uniquely suited to facilitate melanoma staging. Here, scattering properties (related to tissue morphology) are differentiated between the lesion and underlying tissue by leveraging the relative penetration of light from the visible to near infrared. Using models of light transport, we can estimate which fraction of each wavelength will visit the lesion vs dermal tissue, disentangling the scattering features from each tissue volume and determine the depth of pigmented lesion invasion.

Photos and charts showing results from the research.

Project #3: Sub-diffusive Spatial Frequency Domain Imaging

This project seeks to apply SFDI methodologies within sub millimeter volumes of tissue.  The challenge in this regime is that standard SFDI models of light scattering and light transport no longer adequately describe the behavior of light when only a few scattering events occur.  Our group is developing models and methods to describe the behavior of structured light to extend SFDI techniques into the sub-diffusive regime.  This problem is approached from both theoretical (modeling and simulation) and experimental perspectives. 

As scattering within this regime may no longer be described in terms of spatial frequency response alone, we have added new measurement geometries and complementary physical parameters to be able to better isolate and characterize these more subtle light scattering parameters in biological tissues. The addition of angular resolution/sensitivity to standard SFDI measurements is but one approach our group is exploring.


Why is there interest in sub-diffusive modeling and measurement of in vivo tissue? This approach presents the opportunity to:

  • Alter volume of tissue interrogated by “detected” light (photon gating) and not just the frequency of the illumination pattern and thereby reduce the issues posed in quantitative image reconstruction in optical tomography
  • Increase the sensitivity and depth resolution of wide field imaging techniques within superficial volumes: bridge gap between macroscopic and microscopic imaging (i.e. multiply vs singularly scattered light)
  • Extract more subtle, detailed parameters from tissue scattering, in vivo:
    • Extracellular order and regularity, e.g. collagen formation and orientation
    • Shape, complexity of subcellular objects, e.g. Pleomorphism, organelle structure

Project members