Computational analysis of wide-angle light scattering from single cells

• Author / Creator

  Pilarski, Patrick Michael

• The analysis of wide-angle cellular light scattering patterns is a challenging problem. Small changes to the organization, orientation, shape, and optical properties of scatterers and scattering populations can significantly alter their complex two-dimensional scattering signatures. Because of this, it is difficult to find methods that can identify medically relevant cellular properties while remaining robust to experimental noise and sample-to-sample differences. It is an important problem. Recent work has shown that changes to the internal structure of cells---specifically, the distribution and aggregation of organelles---can indicate the progression of a number of common disorders, ranging from cancer to neurodegenerative disease, and can also predict a patient's response to treatments like chemotherapy. However, there is no direct analytical solution to the inverse wide-angle cellular light scattering problem, and available simulation and interpretation methods either rely on restrictive cell models, or are too computationally demanding for routine use. This dissertation addresses these challenges from a computational vantage point. First, it explores the theoretical limits and optical basis for wide-angle scattering pattern analysis. The result is a rapid new simulation method to generate realistic organelle scattering patterns without the need for computationally challenging or restrictive routines. Pattern analysis, image segmentation, machine learning, and iterative pattern classification methods are then used to identify novel relationships between wide-angle scattering patterns and the distribution of organelles (in this case mitochondria) within a cell. Importantly, this work shows that by parameterizing a scattering image it is possible to extract vital information about cell structure while remaining robust to changes in organelle concentration, effective size, and random placement. The result is a powerful collection of methods to simulate and interpret experimental light scattering signatures. This gives new insight into the theoretical basis for wide-angle cellular light scattering, and facilitates advances in real-time patient care, cell structure prediction, and cell morphology research.

• Subjects / Keywords

  • Cytometry
  • Mitochondria
  • Wide-angle light scattering
  • Scattering theory
  • Electrical engineering
  • Image analysis
  • Pattern recognition
  • Optics
  • Reverse monte carlo
  • Computer engineering
  • Pattern analysis
  • Cancer
  • Single cells
  • Generate and test
  • Cell morphology
  • Inverse analysis
  • Image parameterization
  • Iterative methods
  • Fourier transform
  • Machine learning
  • Inverse scattering problem
  • Scattering simulation
  • Medical diagnostics
  • Optical simulation
  • Light scattering
  • Computational intelligence
  • Structure prediction
  • Shape recognition
  • Image processing
  • 3D structure prediction
  • Computational analysis
  • Computer science
  • Biomedical image analysis
  • Cellular optics
  • Lab on a chip
  • Fourier theory

• Graduation date

  2009-11

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R33698

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.