Cell Tracking Using a Multiple
Model Kalman Filter Approach
The Problem:
• Cells observed through microscope move unpredictably
  over time
• May need to track individual cells as they move through
  a solution
  ▫ May need to track multiple cells simultaneously
  Possible cell characteristics to track:
      Movement
      Splits (via mitosis)
      Size
      Interaction with other cells
The Motivation:
 • Want to track cell development over time
 • Need consistency in marking cell phases, splits, etc.
 • Cell behavior is erratic and human estimation is
   subjective
OBJECTIVE:
Using several state-space models of cell motion, estimate cell trajectories using
the appropriate Kalman filter. Compare filter performance for individual
models and propose potential improvements.
The Data:
  • Video of yeast cells in solution*
      • Time-lapsed view of cells
          • Note: It is possible that actual time between when consecutive frames were
            collected varies during video
      • Video frame rate = 10 fps
  • Cells in video have access to ‘nutrient canal’ that contributes to their
    development
  • Multiple cell splits are visible
  • Truth data was generated by determining the position of a single cell
    throughout the entire video
      • This will be used to model the “perfect” sensor measurements
* Data provided by Phil Burlina (JHU APL)
The Challenges:
            Dynamics                            Measurement
-Collective cell motion is random     - Cells are similar in size and shape
-Individual cells move                - Few (if any) distinguishing
unpredictably (No definitive state-   features
space model)
                                      - Grayscale video provides
- Cell interactions are complicated   additional complexity
and not easily modeled
                                      - Cell splits occur quickly and are
                                      difficult to detect
The Measurements:
Matched Filter (MF)                           Problems:
• Cell of interest (from previous             ▫ Cells are similar size
  measurement) compared with                  ▫ Matched filter is not rotation
  frame centered at predicted position          invariant
   ▫ Coordinates of highest MF value          ▫ Grayscale image lacks
     used as position measurement               dynamic range of values
 • Other Variations/Methods:
   ▫ Apply threshold and use association methods to determine closest
     measurement to predicted position
   ▫ Circle detection and center estimate associated with predicted position
   ▫ Use of binary edge detected image instead of full grayscale image
Matched Filter Results:
   Original Frame
                          Template           Edge Detected
                                     - Matched filter provides
                                     reasonable results when cell
                                     shape does not change
                                     - Matched filter not robust enough
                                     to handle subtle changes in cell
                                     shape/orientation
                                     - Errors accumulate over time
                                     because measurements become
                                     correlated
The Models:
     Recall: Cell motion is not predictable and precise state-space models do not exist
                                  Potential State-Space Models
   Linear Motion                         Random Walk                                    Spring Forces
               σw = 8 pix                                                         Modeled as nonlinear process
                                            σw = 25 pix                                       σw = 8 pix
Linear Kalman Filter                  Linear Kalman Filter                        Extended Kalman Filter
            σR = 10 pix ~ cell size                       Cell states initialized to true position, zero velocity
The Interacting Multiple Model (IMM) Filter:
• The IMM filter combines state estimates from individual models
  into a single estimate
   ▫ Each model represented as a “state” in Markov chain
   ▫ IMM filter weights predictions based on probability that any
     given model is correct
                               PRL
                                                           Random Walk
                                     PLR
         Linear Motion
                                                           PRS
                                                                         PSR
                         PLS
                                           Spring Forces
                   PSL
The Results:
• A single cell trajectory was tracked during simulation
   ▫ First, ran simulation without IMM filter. Then, with IMM filter.
• Individual motion models had inconsistent performance
• Initial model probabilities equal (i.e. pj = 1/3, all j)
   ▫ Transition probabilities: P1j = [0.5, 0.25, 0.25]
   ▫ (i.e. equally likely to switch to other model or stay at current one)
• IMM Filter more accurately combines state estimates
       Less estimate ‘drift’ from true state
       Significant error due to individual models is mitigated by IMM filter
 Truth data was used to generate individual and IMM filter results due to inconsistencies with the
 measurement model. Analysis was conducted using measurements via image processing, but
 results were inconsistent and sufficiently inaccurate.
  Cell Trajectory (with KF estimates):
In general, individual models tend to over-predict cell position. While predictions do not deviate significantly
from the true trajectory, there are noticeable errors which may make tracking more difficult.
RMS Errors:
Linear motion model is reasonably accurate with   Random walk begins to drift as   Spring model consistently
errors consistently within the RMS bounds         motion becomes more linear       ‘overshoots’ correct position
IMM Filter Model Probabilities:
                         - Relationship between model
                         probabilities is as expected
                         - Linear Motion model consistently
                         more likely than other two models
                         but there is good tradeoff between
                         models
                         - Model probabilities in IMM filter
                         are strongly coupled with a priori
                         knowledge of system
Potential Improvements
                      Kalman Filter
- Swimming motion model
- Incorporate environmental parameters (viscosity/density)
- Track cell size/shape
- Model cell interactions (attraction/repulsion, effects due to
growth/splits)
- Multiple Hypothesis Tracking
                                            Monte Carlo Simulation
                             Parameters:
                             - Model switching probabilities
                             - Measurement noise variance
                             - Process noise variance
                             - Frame/Gate size
                                                                              Measurement Model
                                                                  - Shape/Rotation invariance
                                                                  - Detect new cell formation
                                                                  - Study cell properties to identify potential features
                                                                  for extraction/tracking
Conclusions and Lessons Learned
• IMM filter provides effective analytical way to combine state-space model
  predictions when true model is unknown
• Tuning Kalman filter to achieve optimal performance is challenging
  ▫ Inaccurate assessment of measurement/process models results in
    significant tracking inaccuracies
• Intuitively, KF performance is constrained by measurement inaccuracies
   ▫ When measurement errors are combined with state-space model
     uncertainties, tracking accuracy becomes degraded
• Identification of individual cells via image processing requires robust
  methods due to similarities in cell size, shape, orientation, and pixel intensity
• Other variations of KF were implemented but were still not completely
  accurate due to lack of understanding of cell motion model
References
1.   R.G. Brown and P. Hwang, Introduction to Random Signals and Applied Kalman
     Filtering, New York: Wiley, 1997.
2.   W.D. Blair, “Derivation of Interacting Multiple Model Algorithm for Systems with
     Markovian Switching Coefficients”.
3.   J. Samsundar and A. Watkins, 525.745 Applied Kalman Filtering Lecture Notes,
     2011.
4.   P. Burlina, private communication, March 2011.