Difference between revisions of "Support:Documents:Examples:Estimate Change Neurotransmitter"

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==== Tissue uptake ====
 
This model has one tissue compartment.  Material in the blood is assumed to rapidly exchange with that in (extravascular) tissue.
 
This model has one tissue compartment.  Material in the blood is assumed to rapidly exchange with that in (extravascular) tissue.
 
The tissue model has two rate constants: K<sub>1</sub> and k<sub>2</sub> and is depicted in the diagram:
 
The tissue model has two rate constants: K<sub>1</sub> and k<sub>2</sub> and is depicted in the diagram:
  
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[[Image:ExampleFigureBloodFlowModel.png]]
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==== Input function ====
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It can also be described by the differential equation:
 
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dC<sub>T</sub>/dt = K<sub>1</sub> C<sub>p</sub> - k<sub>2</sub> C<sub>T</sub>
 
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where C<sub>T</sub> is the tissue concentration and C<sub>p</sub> is the plasma concentration.
 
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C<sub>T</sub> and C<sub>p</sub> are interpreted as either molar concentrations ([http://www.ncbi.nlm.nih.gov/pubmed/17555251?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Salinas, Muzic and Saidel 2007]).
 
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This example also demonstrates how to temporally align measured input function data to the tissue (image) data.  Here the plasma concentration vs. time t is modeled as
 
This example also demonstrates how to temporally align measured input function data to the tissue (image) data.  Here the plasma concentration vs. time t is modeled as
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C<sub>p</sub>(t, tau) = M(t-tau) if t >= tau;  0 if t < tau .
 
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M(t) is the measured input data, tau is the delay parameter to estimate, and t is the time in minutes.
 
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Because the delay tau is estimated in this example, it will be handy to note that derivative of the input with respect to delay is
 
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dC<sub>p</sub>(t)/d tau = - dM/dt|<sub>t-tau</sub>
 
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For this example, M is determined by using linear interpolation to interpolate between measured values.  The interpolation is implemented using piecewise polynomial framework (and it could be easily modified to accommodate cubic spline interpolation).
 
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Let inputData be a two-column matrix with column 1 holding sample times and column 2 holding the sampled input concentrations. 
 
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The interpolation coefficients may be calculated using the lspline function
 
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<pre>
 
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ppM = lspline(inputData(:,1), inputData(:,2));
 
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</pre>
 
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To evaluate the derivative dC<sub>p</sub>/dt, which can be determined in terms of dM/dt by analytically differentiating the interpolating polynomial.
 
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<pre>
 
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[breaks, coefs, l, k, d] = unmkpp(ppM);
 
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ppdMdtau = mkpp(breaks, repmat(k-1:-1:1,d*l,1) .* coefs(:,1:k-1), d);
 
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</pre>
 
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The input function is then implemented as
 
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<pre>
 
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function [Cp, dCpdtau] = DelayExampleInput(parm, t, X)
 
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if (nargout > 0),
 
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    t = t(:); % ensure t is a column vector
 
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    tau = parm(1);  % delay
 
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    ppC = X{1}; % piecewise-polynomial coefficients for Cp
 
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    Cp = zeros(size(t));
 
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    f = find(t > tau);
 
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    Cp(f) = ppval(ppC, t(f) - tau);
 
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    if (nargout > 1),
 
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        ppdCdt = X{2}; % piecewise-polynomial coefficients for derivative
 
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        dCpdtau = zeros(size(t));
 
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        dCpdtau(f) = -ppval(ppdCdt, t(f) - tau);
 
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    end
 
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end
 
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</pre>
 
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== Example:  Estimating Input Delay and Rate Constants ==
 
== Example:  Estimating Input Delay and Rate Constants ==
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In this example, the model output are assumed to represent measurements of C<sub>T</sub>.  (To keep the example simple, intravascular concentration of tracer is ignored.)
 
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The values of the parameters p = [K<sub>1</sub>; k<sub>2</sub>; tau] will be estimated.
 
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'''Step 1''' To set the simulation in Matlab, create the above function and put in in a file called DelayExampleInput.m.
 
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'''Step 2''' Create a 1-tissue compartment model
 
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<pre>
 
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% create new, empty model
 
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cm = compartmentModel;
 
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% define default values for parameters
 
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cm = addParameter(cm, 'k1', 0.3);
 
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cm = addParameter(cm, 'k2', 0.5);
 
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cm = addParameter(cm, 'tau', 0.25);
 
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cm = addParameter(cm, 'sa', 1);    % specific activity at t=0
 
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cm = addParameter(cm, 'dk', 0.34); % decay constant
 
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cm = addParameter(cm, 'tau', 0.25); % time delay
 
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% add compartments
 
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cm = addCompartment(cm, 'CT');
 
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cm = addCompartment(cm, 'J');
 
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% define the input(first column is time, second it concentration)
 
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inputData = [
 
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        0            0
 
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    0.0500        0
 
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    0.1000        0
 
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    0.1500  14.5234
 
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    0.2000  52.1622
 
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    0.2500  76.6730
 
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    0.3000  91.6416
 
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    0.4000  103.0927
 
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    0.5000  100.9401
 
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    0.7000  83.5343
 
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    0.8000  74.3628
 
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    1.0000  59.7726
 
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    1.2500  48.7530
 
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    1.5000  43.0772
 
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    1.7500  40.1924
 
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    2.0000  38.6236
 
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];
 
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% determine spline coefficients for linear interpolation
 
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ppM = lspline(inputData(:,1), inputData(:,2));
 
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% analytically calculate derivative
 
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[breaks, coefs, l, k, d] = unmkpp(ppM);
 
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ppdMdtau = mkpp(breaks, repmat(k-1:-1:1,d*l,1) .* coefs(:,1:k-1), d);
 
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X = {ppM, ppdMdtau};
 
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cm = addInput(cm, 'Cp','sa','dk', 'DelayExampleInput', 'tau', X);
 
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% connect compartments and inputs
 
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cm = addLink(cm, 'L', 'Cp', 'CT', 'k1');
 
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cm = addLink(cm, 'K', 'CT', 'J', 'k2');
 
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% define the activity concentration in tissue pixel
 
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cm = addOutput(cm, 'TissuePixel', {'CT','1'}, {'Cp','0'});
 
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% specify scan frame times
 
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st = [[0:5:85]' [5:5:90]']/60;  % division by 60 converts sec to min
 
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cm = set(cm, 'ScanTime', st);
 
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midScanTime = (st(:,1) + st(:,2)) / 2;
 
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% solve the model and generate the output
 
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[sol,solIndex] = solve(cm);
 
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plot(midScanTime,sol(:,3),'LineWidth',2);
 
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xlabel('Minutes');
 
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ylabel('KBq/ml');
 
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</pre>
 
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[[Image:Pretest.jpeg]]
 
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The above figure is the model output (C<sub>T</sub>). Here, we use it as perfect experimental data that would be fitted.
 
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'''Step 3''' Use model output as measured C<sub>T</sub> (perfect "data") and fit it
 
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<pre>
 
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% Set parameters: initial guess, lower and upper bounds for K1, k2 and tau
 
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pinit=[0.1;0.2;0.1];
 
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lb  =[0.01;0.01;0.01];
 
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ub  =[1;1;5];
 
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% specify parameters to be adjusted in fitting
 
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cm=addSensitivity(cm,'k1','k2','tau');
 
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% Experimental Data to be fit
 
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cm=set(cm,'ExperimentalData',sol(:,3));
 
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% Perform curve fitting
 
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[pfit,qfitnull,modelfit,pp1,output]=fitGen(cm,pinit,lb,ub,'OLS');
 
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</pre>
 
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'''Step 4''' Examine model outputs using estimated parameter (pfit) and initial guess (pinit)
 
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<pre>
 
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% Solve model using estimated parameters
 
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cm1=cm;
 
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cm1=set(cm1,'ParameterValue','k1',pfit(1));
 
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cm1=set(cm1,'ParameterValue','k2',pfit(2));
 
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cm1=set(cm1,'ParameterValue','tau',pfit(3));
 
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est_sol=solve(cm1);
 
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% solve model using initial parameters
 
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cm1=set(cm1,'ParameterValue','k1',pinit(1));
 
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cm1=set(cm1,'ParameterValue','k2',pinit(2));
 
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cm1=set(cm1,'ParameterValue','tau',pinit(3));
 
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est_sol_init=solve(cm1);
 
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plot(midScanTime,sol(:,3),'o',midScanTime,est_sol(:,3),'r-',midScanTime,est_sol_init(:,3),'g-','LineWidth',2);
 
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xlabel('Minutes');
 
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ylabel('KBq/ml');
 
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legend('Data', 'Fit','Initial Guess');
 
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</pre>
 
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[[Image:test.jpeg]]
 

Revision as of 00:40, 24 February 2009

Estimating Input Delay and Rate Constants

This example demonstrates an approach to simultaneously estimating input function delay along with parameters of the 1-tissue compartment (e.g. blood flow) model. For the sake of generality, this could be interpreted as a dynamic contrast-enhanced (DCE) MRI or perfusion PET study.


Tissue uptake

This model has one tissue compartment. Material in the blood is assumed to rapidly exchange with that in (extravascular) tissue. The tissue model has two rate constants: K1 and k2 and is depicted in the diagram:

Input function

This example also demonstrates how to temporally align measured input function data to the tissue (image) data. Here the plasma concentration vs. time t is modeled as

Example: Estimating Input Delay and Rate Constants

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