A Logan plot (or Logan graphical analysis)[1] is a graphical analysis technique based on the compartment model that uses linear regression to analyze pharmacokinetics of tracers involving reversible uptake. It is mainly used for the evaluation of nuclear medicine imaging data after the injection of a labeled ligand that binds reversibly to specific receptor or enzyme.
In conventional compartmental analysis, an iterative method is used to fit the individual model parameters in the solution of a compartmental model of specific configuration to the measurements with a measured plasma time-activity curve that serves as an forcing (input) function, and the binding of the tracer can then be described. Graphical analysis is a simplified method that transforms the model equations into a linear equation evaluated at multiple time points and provides fewer parameters (i.e., slope and intercept). Although the slope and the intercept can be interpreted in terms of a combination of model parameters if a compartmental model configuration is assumed, the graphical methods are independent of any specific model configuration. In case of irreversible tracers, certain fraction of the radioactivity is trapped in the tissue or the binding site during the course of the experiment, whereas reversible tracers show uptake and loss from all compartments throughout the study. The theoretical foundation of graphical analysis for irreversible tracers (also called Patlak graphical analysis or Patlak plot) was laid by Clifford Patlak and his colleagues[2] [3] at NIH. Based on the original work of Patlak, Jean Logan and her colleagues from Brookhaven National Laboratory extended the method to tracers with reversible kinetics.
The kinetics of radiolabeled compounds in a compartmental system can be described in terms of a set of first-order, constant-coefficient, ordinary differential equations.[4] [5] The time course of the activity in the multicompartmental system driven by a metabolite-corrected plasma input function
Cp(t)
| dA | |
| dt |
=KA+QCp(t)
where
A
t
K
Q
| t | |
| \int | |
| 0 |
A(\tau)d\tau=
| T | |
| -U | |
| n |
K-1Q
| t | |
| \int | |
| 0 |
Cp(\tau)d\tau+
| T | |
| U | |
| n |
K-1A
where
| T | |
| U | |
| n |
A(t)=
| T | |
| U | |
| n |
A
ROI(t)
Vp
| t | |
| \int | |
| 0 |
ROI(\tau)d\tau=
| T | |
| (-U | |
| n |
K-1Q+Vp)
| t | |
| \int | |
| 0 |
Cp(\tau)d\tau+
| T | |
| U | |
| n |
K-1A
By dividing both sides by
ROI(t)
| t | |
| {{\int | |
| 0 |
ROI(\tau)d\tau}\overROI(t)}=
| T | |
| (-U | |
| n |
K-1Q+Vp)
| t | |
| {{\int | |
| 0 |
Cp(\tau)d\tau}\overROI(t)}+
| T | |
| {{U | |
| n |
K-1A
For
t>t'
A=-K-1QCp(t)
| t | |
| {{\int | |
| 0 |
Cp(\tau)d\tau}\overROI(t)}
| t | |
| {{\int | |
| 0 |
ROI(\tau)d\tau}\overROI(t)}
| T | |
| (-U | |
| n |
K-1Q+Vp)
| T | |
| {{U | |
| n |
K-1A
For a catenary two-tissue compartment model with transfer constants
K1
k2
k3
Bmaxkon
k4
Vd
| K1 | (1+ | |
| k2 |
| k3 | |
| k4 |
)+Vp
k3=Bmaxkon
k4=koff
| k3 | |
| k4 |
=
| Bmax | |
| Kd |
Kd=koff/kon
Bmax
Kd
kon
koff
K1
k2
λ+Vp
λ
{K1}/{k2}
| -1 | |
| k2(1+Vp/λ) |