Modeling of pharmaceutical propagation and parameter generation for injection protocols

• US 9,959,389 B2
• Filed: 06/24/2011
• Issued: 05/01/2018
• Est. Priority Date: 06/24/2010
• Status: Active Grant

• Current Assignee: Bayer Healthcare LLC (Bayer AG)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Kalafut, John F.
• Primary Examiner(s): Roy, Baisakhi
• Application Number:
  US13/806,121
• Publication Number:
  US 20130211247A1
• Time in Patent Office: 2,503 Days
• Field of Search: 600431, 600432
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

A system includes a parameter generation system to determine at least one parameter for an injection procedure (for example, a parameter of an injection protocol or an imaging system parameter), the parameter generator system includes a physiologically based pharmacokinetic model to model propagation of a contrast medium injected into a patient including at least one of a non-linear saturation term in a peripheral venous compartment, at least one configurable transport delay term through at least one compartment, or an adaptation to model volumetric flow rate of blood and an effect thereof on the propagation of contrast medium after injection of contrast medium ceases. The physiologically based pharmacokinetic model can, for example, be discretizable.

Claims

1. A method of controlling injection of a contrast medium comprising a contrast enhancing agent into a patient in an injection procedure, the method comprising:

providing a control system operably associated with a first pressurizing drive member, the first pressurizing drive member being adapted to be operably associated with at least a first fluid container, and the first fluid container being adapted to contain the contrast medium; and

determining at least one parameter for the injection procedure via which the control system controls the first pressurizing drive member by modeling, prior to the injection procedure, propagation of the contrast medium to be injected into the patient using a physiologically based pharmacokinetic model stored in a memory system in connection with the control system, wherein the physiologically based pharmacokinetic model has incorporated therein a non-linear saturation term in a peripheral venous compartment, wherein exogenous administration of the contrast enhancing agent is provided by the equation u_exog(t)=C_inj(t)·

Q_inj(t) wherein C_inj(t) is a concentration of the contrast enhancing agent as a function of time and Q_inj(t) is an administration flow rate of contrast as a function of time, but wherein Q_inj(t) is a constant equal to a predetermined limiting administration flow rate at administration flow rates equal to or greater than the limiting administration flow rate.

2. The method of claim 1, wherein the physiologically based pharmacokinetic model is adapted to estimate a time enhancement curve for a region of interest of the patient.

3. The method of claim 2, further comprising:

using the physiologically based pharmacokinetic model to estimate the time enhancement curve for the patient; and

determining at least one parameter of the injection procedure at least in part on the basis of the estimated time enhancement cure.

4. The method of claim 1, wherein the physiologically based pharmacokinetic model is adapted to model propagation of the contrast medium after injection of the contrast medium has ceased.

5. The method of claim 4, wherein the physiologically based pharmacokinetic model models a volumetric flow rate of blood and an effect thereof on propagation of the contrast medium.

6. The method of claim 5 wherein the physiologically based pharmacokinetic model models the effect on propagation of the contrast medium upon injection of a fluid containing no contrast enhancing agent after injection of the contrast medium, wherein the effect of volumetric flow rate of exogenous fluid on the volumetric flow rate of blood is considered in the physiologically based pharmacokinetic model.

7. The method of claim 1, wherein at least one parameter for the physiologically based pharmacokinetic model is determined at least partially on the basis of data from multiple individuals.

8. The method of claim 1, wherein at least one parameter for the physiologically based pharmacokinetic model is determined at least partially on the basis of at least one patient specific variable.

9. The method of claim 1, wherein at least one parameter for the physiologically based pharmacokinetic model is determined at least in part from at least one time enhancement curve of the patient resulting from an injection of the contrast medium.

10. The method of claim 1, wherein the physiologically based pharmacokinetic model is incorporated in a system comprising an injector system and an imaging system and is used in generating at least one parameter for the injection procedure.

11. The method of claim 1 further comprising:

incorporating into the physiologically based pharmacokinetic model at least one configurable transport delay term through at least one compartment.

12. The method of claim 11, wherein the at least one configurable transport delay term is configurable at least in part on the basis of at least one patient specific variable.

13. A method of controlling injection of a contrast medium including a contrast enhancing agent into a patient in an in procedure, the method comprising:

providing a control system operably associated with a first pressurizing drive member, the first pressurizing drive member being adapted to be operably associated with at least a first fluid container, and the first fluid container being adapted to contain the contrast medium; and

determining at least one parameter for the injection procedure via which the control system controls the first pressurizing drive member by modeling, prior to the injection procedure, propagation of the contrast medium to be injected into the patient using a compartmental physiologically based pharmacokinetic model comprising a peripheral venous compartment, wherein the compartmental physiologically based pharmacokinetic model is saved in a memory system in connection with the control system, the determining comprising;

modeling a volumetric flow rate of blood and an effect thereof on the propagation of contrast medium comprising inclusion of a parameter for a volumetric flow rate of an exogenous fluid in the physiologically based pharmacokinetic model, wherein the volumetric flow rate of blood and the volumetric flow rate of the exogenous fluid are treated independently and the effect of the volumetric flow rate of the exogenous fluid on the volumetric flow rate of blood is considered in mass balances in the peripheral venous compartment of the compartmental physiologically based pharmacokinetic model.

14. The method of claim 13, wherein the compartmental physiologically based pharmacokinetic model models an effect on propagation of the contrast medium upon injection of a fluid containing no contrast enhancing agent after injection of the contrast medium.

15. The method of claim 14, wherein the compartmental physiologically based pharmacokinetic model is adapted to estimate a time enhancement curve for a region of interest of the patient.

16. The method of claim 15, further comprising:

using the compartmental physiologically based pharmacokinetic model to estimate the time enhancement curve for the patient; and

determining at least one parameter of the injection procedure at least in part on the basis of the estimated time enhancement curve.

17. The method of claim 16, further comprising:

using the time enhancement curve during a diagnostic injection of the contrast medium to update the compartmental physiologically based pharmacokinetic model and to alter at least one parameter of the injection procedure.

18. The method of claim 14, wherein the compartmental physiologically based pharmacokinetic model comprises at least one non-linear saturation term in the peripheral venous compartment or at least one configurable transport delay term through at least one compartment.

19. The method of claim 14, wherein at least one parameter for the compartmental physiologically based pharmacokinetic model is determined at least in part on the basis of data from multiple individuals.

20. The method of claim 14, wherein at least one parameter for the compartmental physiologically based pharmacokinetic model is determined at least partially on the basis of at least one patient specific variable.

21. The method of claim 14, wherein at least one parameter for the compartmental physiologically based pharmacokinetic model is determined at least in part on the basis of at least one time enhancement curve of the patient resulting from an injection of the contrast medium.

22. A system comprising:

a first pressurizing drive member adapted to be operably associated with at least a first fluid container, the first fluid container being adapted to contain a contrast medium comprising a contrast enhancing agent;

a control system operably associated with the first pressurizing drive member;

a memory system in connection with the control system; and

a parameter generation system stored in the memory system to determine at least one parameter via which the control system controls the first pressurizing drive member during an injection procedure, the parameter generator system comprising a physiologically based pharmacokinetic model to model, prior to the injection procedure, propagation of the contrast medium to be injected into a patient, the physiologically based pharmacokinetic model comprising a non-linear saturation term in a peripheral venous compartment, wherein exogenous administration of the contrast enhancing agent is provided by the equation u_exog(t)=C_inj(t)·

Q_inj(t) wherein C_inj(t) is a concentration of the contrast enhancing agent as a function of time and Q_inj(t) is an administration flow rate of contrast as a function of time, but wherein Q_inj(t) is a constant equal to a predetermined limiting administration flow rate at administration flow rates equal to or greater than the limiting administration flow rate.

23. The system of claim 22, wherein at least one parameter for the physiologically based pharmacokinetic model is determined at least in part from at least one time enhancement curve of the patient.

24. The system of claim 22, further comprising:

non-parametric model to model propagation of the contrast medium injected into the patient.

25. The system of claim 24, wherein the at least one parameter is determined using an optimization method on the basis of at least one of the physiologically based pharmacokinetic model or the non-parametric model.

26. The system of claim 22, wherein the at least one parameter is determined using an optimization method on the basis of the physiologically based pharmacokinetic model.

27. The system of claim 22, wherein the physiologically based pharmacokinetic model further comprises at least one configurable transport delay term through at least one compartment.

28. The system of claim 22, wherein the physiologically based pharmacokinetic model further comprises an adaptation to model a volumetric flow rate of blood and an effect thereof on the propagation of the contrast medium after injection of the contrast medium ceases, wherein the effect of volumetric flow rate of exogenous fluid on the volumetric flow rate of blood is considered in the physiologically based pharmacokinetic model.