## p2t_di - tpcclib 0.7.4 © 2019 by Turku PET Centre

```Simulation of PET tissue time-radioactivity concentration curve (TTAC) using
dual-input four-tissue compartmental models. Input consists of parent tracer
and metabolite concentration curves in arterial plasma (Cap and Cam) and
total radioactivity concentration in arterial blood (Cb).

Tissue compartments for parent tracer are in series [1] (by default):

_____    K1   ____    k3   ____    k5   ____    k7
| Cap | ----> | C1 | ----> | C2 | ----> | C3 | ---->
|_____| <---- |____| <---- |____| <---- |____|
k2     |     k4           k6
km|
v
_____   K1m   ____
| Cam | ----> | C4 |
|_____| <---- |____|
k2m

dC1(t)/dt = K1*Cap(T) - (k2+k3+km)*C1(T) + k4*C2(T)
dC2(t)/dt = k3*C1(T) - (k4+k5)*C2(T) + k6*C3(T)
dC3(t)/dt = k5*C2(T) - (k6+k7)*C3(T)
dC4(t)/dt = K1m*Cam(T) + km*C1(T) - k2m*C4(T)
Ct(T) = C1(T) + C2(T) + C3(T) + C4(T)
Cvb(T) = Cab(T) - dCt(t)/dt / f
Cpet(T)= Vb*fA*Cab(T) + Vb*(1-fA)*Cvb(T) + (1-Vb)*Ct(T)

, or, optionally, the 2nd and 3rd tissue compartments are parallel [2],
often used to represent specific and non-specific binding:

____
| C3 |   k7
|____| ---->
^ |
k5 | | k6
| v
_____    K1   ____    k3   ____
| Cap | ----> | C1 | ----> | C2 |
|_____| <---- |____| <---- |____|
k2     |     k4
km|
v
_____   K1m   ____
| Cam | ----> | C4 |
|_____| <---- |____|
k2m

dC1(t)/dt = K1*Ca(T) - (k2+k3+k5+km)*C1(T) + k4*C2(T) + k6*C3(T)
dC2(t)/dt = k3*C1(T) - k4*C2(T)
dC3(t)/dt = k5*C2(T) - (k6+k7)*C3(T)
dC4(t)/dt = K1m*Cam(T) + km*C1(T) - k2m*C4(T)
Ct(T) = C1(T) + C2(T) + C3(T) + C4(T)
Cvb(T) = Cab(T) - dCt(t)/dt / f
Cpet(T)= Vb*fA*Cab(T) + Vb*(1-fA)*Cvb(T) + (1-Vb)*Ct(T)

Usage: p2t_di [options] parentfile metabolitefile bloodfile K1 k2 k3 k4 k5 k6 k7 km K1m k2m Vb simfile

Options:
-paral[lel]
Model with parallel compartments C2 and C3 is applied.
-ser[ies]
Model with compartments C1, C2, and C3 in series is applied (default).
-sub | -nosub
TACs of sub-compartments (C1, C2 and C3) are written (-sub)
or not written (-nosub, default) into the output file.
-f=<Perfusion (ml/(min*ml) or ml/(sec*ml))>
Difference between concentrations in venous and arterial blood can
be simulated if tissue perfusion (f>K1) is specified with this option
and arterial fraction of vascular volume is set with option -fA;
by default it is assumed that venous and arterial activities are
the same (f>>K1).
-fA=<Arterial fraction of vascular volume (%)>
Difference between concentrations in venous and arterial blood can
be simulated if arterial fraction of vascular volume is specified with
this option and tissue perfusion is set with option -f;
by default it is assumed that Vb consists of only arterial blood.
-h, --help
Display usage information on standard output and exit.
-v, --version
Display version and compile information on standard output and exit.
-d[n], --debug[=n], --verbose[=n]
Set the level (n) of debugging messages and listings.
-q, --quiet
Suppress displaying normal results on standard output.
-s, --silent
Suppress displaying anything except errors.

If the times in plasma file are in seconds, the units of rate constants
(k's) and blood flow (f) must also be specified as 1/sec.
For accurate results, plasma TAC should have very short sampling intervals.
To reduce the model, k7, k5, and k3 can be set to 0.

Simulated TACs are written in ASCII format with columns:
1) Sample time
2) Total tissue activity concentration (Cpet)
3) Activity concentration in 1st tissue compartment, (1-Vb)*C1 (optional)
4) Activity concentration in 2nd tissue compartment, (1-Vb)*C2 (optional)
5) Activity concentration in 3rd tissue compartment, (1-Vb)*C3 (optional)
6) Activity concentration in 4th tissue compartment, (1-Vb)*C4 (optional)
7) Arterial contribution to tissue activity, Vb*fA*Cab (optional)
8) Venous contribution to tissue activity, Vb*(1-fA)*Cvb (optional)

References:
1. TPCMOD0001 Appendix B.
2. TPCMOD0001 Appendix C.