title: A quantitative framework for the analysis of multimodal optical microscopy images.
abstract: BACKGROUND
  Multimodal optical microscopy, a set of imaging techniques based on unique, yet complementary contrast mechanisms and spatially and temporally co-registered data acquisition, has emerged as a powerful biomedical tool. However, the analysis of the dense, high-dimensional datasets acquired by these instruments remains mostly qualitative and restricted to analysis of each modality individually.
  
  
  METHODS
  Using a custom-built multimodal nonlinear optical microscope, high dimensional datasets were acquired for automated classification of functional cell states as well as identification of histopathological features in tissues slices. Supervised classification of cell death modes was performed through support vector machines (SVM) and semi-supervised classification of tissue slices was performed through the use of the expectation maximization (EM) algorithm.
  
  
  RESULTS
  Applications of these techniques to the automated classification of cell death modes as well as to the identification of tissue components in fixedex vivotissue slices are presented. The analysis techniques developed provide a direct link between multimodal image contrast and biological structure and function, resulting in highly accurate classification in both settings.
  
  
  CONCLUSIONS
  Quantification of multimodal optical microscopy images through statistical modeling of the high dimensional data acquired gives a strong correlation between biological structure and function and image contrast. These methods are sensitive to the identification of diagnostic, cellular-level features important in a variety of clinical settings.
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bower
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chidester
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Li
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Youbo
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Marjanovic
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chaney
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Minh N
authors.initials: MN
authors.lastname: Do
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Internal Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boppart
keywords: Optical imaging; image processing; multimodal imaging; optical microscopy