Systems and methods of determining patient transfer functions and modeling patient response to a pharmaceutical injection

• US 8,295,914 B2
• Filed: 11/16/2005
• Issued: 10/23/2012
• Est. Priority Date: 11/16/2004
• Status: Active Grant

• Current Assignee: Bayer Healthcare LLC (Bayer AG)
• Original Assignee: Medrad Incorporated (Bayer AG)
• Inventors: Kalafut, John F., Uber, Arthur E. III
• Primary Examiner(s): MENDEZ, MANUEL A
• Application Number:
  US11/575,846
• Publication Number:
  US 20080097197A1
• Time in Patent Office: 2,533 Days
• Field of Search: 604 65- 67, 604/131, 604/30, 604/246, 600431-435
• US Class Current: 600/431
• CPC Class Codes: A61B 5/0044 for the heart
• CPC Class Codes: A61B 5/02028 Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/026 Measuring blood flow A61B3/1233, A61B3/1241 take precedence
• CPC Class Codes: A61B 5/029 Measuring or recording blood output from the heart, e.g. minute volume A61B8/065 takes precedence
• CPC Class Codes: A61B 5/0295 using plethysmography, i.e. measuring the variations in the volume of a body part as modified by the circulation of blood therethrough, e.g. impedance plethysmography
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: A61B 6/032 Transmission computed tomography [CT]
• CPC Class Codes: A61B 6/481 involving the use of contrast agents
• CPC Class Codes: A61B 6/504 for diagnosis of blood vessels, e.g. by angiography
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61B 6/583 using calibration phantoms
• CPC Class Codes: A61B 8/13 Tomography A61B8/10, A61B8/12 take precedence; tomography for radiation diagnosis A61B6/02
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61M 5/007 for contrast media
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: G16H 30/20 for handling medical images, e.g. DICOM, HL7 or PACS
• CPC Class Codes: G16H 30/40 for processing medical images, e.g. editing
• CPC Class Codes: G16H 50/50 : for simulation or modelling of medical disorders

Abstract

A method of controlling an injector system for delivering a contrast enhancing fluid to a patient. The method includes the step of determining at least one patient transfer function for the patient based upon data specific to the patient, with the at least one patient transfer function providing a time enhancement output for a given input. The data specific to the patent may include at least one of an estimate of physiologic parameters of the patient, an estimate of anatomic parameters of the patient and an enhancement caused by an injection of the contrast enhancing fluid into the patient. Other steps involve: determining a desired time enhancement output; using the at least one patient transfer function to determine an injection procedure input; and controlling the injector system at least in part on the basis of the determined injection procedure input.

Claims

1. A method of controlling an injector system for delivering a contrast enhancing fluid to a patient, comprising:

(a) determining at least one patient transfer function for the patient based upon data specific to the patient, the at least one patient transfer function providing a time enhancement output for a given input, the data specific to the patient including at least one of an estimate of physiological parameters of the patient, an estimate of anatomic parameters of the patient and an enhancement caused by an injection of the contrast enhancing fluid into the patient;

(b) determining a desired time enhancement output;

(c) using the at least one patient transfer function to determine an injection procedure input; and

(d) controlling the injector system at least in part on the basis of the determined injection procedure input.

2. The method of claim 1 wherein the contrast enhancing fluid is a CT contrast enhancing fluid, a MRI contrast enhancing fluid, an ultrasound enhancing imaging fluid or a radioactive contrast enhancing fluid.

3. The method of claim 1 wherein at least two patient transfer functions are determined and the injection procedure input is determined on the basis of one of the patient transfer functions.

4. The method of claim 3 wherein a first patient transfer function is determined using a system identification model comprising parameters related to physiological parameters of the patient and a second patient transfer function is determined using a mathematical model determined by collecting data corresponding to a time enhancement curve resulting from an injection, the mathematical model describing the data.

5. The method of claim 3 wherein a determination is made as to which patient transfer function provides a best correlation between a given input and a resulting output.

6. The method of claim 1 wherein the injection procedure input is determined considering at least one operational limitation or constraint of the injector system.

7. The method of claim 6 wherein the at least one patient transfer function is determined by the steps of:

(a) collecting data corresponding to a time response curve resulting from an injection of the fluid; and

(b) determining at least one mathematical model describing the data.

8. The method of claim 7 wherein the mathematical model is not determined by a continuous or a discrete-time Fourier transform of the data.

9. The method of claim 7 wherein the model is a parametric model.

10. The method of claim 9 wherein the model is a moving average or an autoregressive moving average.

11. The method of claim 9 wherein the mathematical model assumes linearity and time invariance.

12. The method of claim 7 wherein the model is a non-parametric model determined by a spectral estimation technique.

13. The method of claim 12 wherein the spectral estimation technique is Welch'"'"'s method, Bartlett'"'"'s method, a multiple signal classification (MUSIC) method, or a Periodogram method.

14. The method of claim 7 wherein data is collected during at least one test injection prior to an imaging injection.

15. The method of claim 7 wherein the at least one patient transfer function is updated with data collected during an imaging injection.

16. The method of claim 6 wherein the injection procedure input is determined using an analytical solution or using a numerical, constrained optimization technique.

17. The method of claim 16 wherein the numerical, constrained optimization technique is a weighted least-squared numerical optimization.

18. The method of claim 16 wherein the injection procedure input is optimized to minimize a mass of a contrast enhancing agent in the contrast enhancing fluid delivered to the patient.

19. The method of claim 18 wherein the contrast enhancing agent is iodine, xenon or gadolinium.

20. The method of claim 6 wherein the at least one patient transfer function is determined using a system identification model comprising parameters related to the physiological parameters of the patient.

21. The method of claim 20 wherein the system identification model is discretizable.

22. The method of claim 20 further comprising the steps of:

(a) developing an initial patient transfer function using estimates of at least one of the physiological parameters of the patient;

(b) performing an injection; and

(c) revising the patient transfer function based upon at least one time enhancement output of the injection.

23. The method of claim 22 wherein the at least one patient physiological parameter is measured from the at least one time enhancement output.

24. The method of claim 22 wherein the injection is a test injection performed prior to a diagnostic imaging procedure.

25. The method of claim 24 wherein time enhancement outputs resulting from the test injection are measured for at least two different regions of interest.

26. The method of claim 25 wherein a first time enhancement output is measured in an ascending aorta or a descending aorta and a second time enhancement output is measured in a pulmonary artery trunk.

27. The method of claim 25 wherein differences between the time enhancement outputs provide a measure of at least one patient physiological parameter.

28. The method of claim 27 wherein a first time enhancement output is measured in an ascending aorta or a descending aorta and a second time enhancement output is measured in a pulmonary artery trunk.

29. The method of claim 28 wherein the at least one patient physiological parameter is cardiac output, blood volume in a region, a rate transfer term or a transit delay.

30. The method of claim 27 wherein the at least one patient physiological parameter is a parameter of the cardiopulmonary system.

31. The method of claim 30 wherein the at least one patient physiological parameter is cardiac output, blood volume in a region, a rate transfer term or a transit delay.

32. The method of claim 20 wherein the at least one patient transfer function is updated with data collected during an imaging injection.

33. The method of claim 6 wherein the at least one patient transfer function is determined at least in part on the basis of at least one injection.

34. The method of claim 33 wherein the at least one injection is a test injection performed prior to a diagnostic imaging procedure.

35. The method of claim 34 wherein more than one test injection is performed.

36. The method of claim 35 where one test injection comprises injection of a contrast medium only and another test injection comprises injection of a contrast medium followed by injection of a non-contrast fluid.

37. The method of claim 34 wherein the test injection comprises injection of a contrast medium followed by injection of a non-contrast fluid.

38. The method of claim 37 wherein the non-contrast fluid is injected at substantially the same volumetric flow rate as a flow rate of the contrast medium preceding the injection of the non-contrast fluid.

39. The method of claim 38 wherein the non-contrast fluid is saline.

40. An injector system for the delivery of a fluid to a patient comprising:

(a) an injector; and

(b) a controller in communicative connection with the injector, the controller comprising;

(I) at least one patient transfer function determined for the patient based upon data specific to the patient, the at least one patient transfer function providing a time enhancement output for a given input, the data specific to the patient including at least one of an estimate of physiologic parameters of the patient, an estimate of anatomic parameters of the patient and an enhancement caused by an injection of the fluid into the patient; and

(II) a processor to determine an injection procedure input for a desired time enhancement output using the at least one patient transfer function.

41. The injector system of claim 40 wherein the injection procedure input is determined considering at least one operational limitation or constraint of the injector.

42. The injector system of claim 40 wherein the injection procedure input is determined using an analytical solution or a numerical, constrained optimization technique.

43. The injector system of claim 42 wherein the numerical, constrained optimization technique is a weighted least-squared numerical optimization.

44. The injector system of claim 42 wherein the injection procedure input is optimized to minimize a mass of a contrast enhancing agent in the fluid delivered to the patient.

45. The injector system of claim 44 wherein the contrast enhancing agent is iodine, xenon or gadolinium.

46. The injector system of claim 40 wherein the fluid is a CT contrast enhancing fluid, a MRI contrast enhancing fluid, an ultrasound enhancing imaging fluid or a radioactive contrast enhancing fluid.

47. A method of controlling an injector in a medical imaging procedure, comprising:

(a) determining at least one mathematical model to predict a time enhancement response resulting from an injection of a contrast medium;

(b) determining an injection protocol to approximate a predetermined time enhancement response in a patient by determining a constrained input solution to the at least one mathematical model; and

(c) using the injection protocol to control the injector during the medical imaging procedure to control the injection of the contrast medium into the patient to create an image of a region of interest.

48. The method of claim 47 further comprising the step of changing the injection protocol as a result of feedback regarding the time enhancement response during the imaging procedure.

49. The method of claim 47 further comprising the step of changing the injection protocol as a result of data regarding at least one patient physiological parameter during the imaging procedure.

50. The method of claim 47 wherein the step of determining an injection protocol to approximate the predetermined time enhancement response is accomplished using a numerical solver or a numerical optimizer.

51. The method of claim 47 wherein the constrained input solution to the mathematical model is constrained by at least one operational limitation of the injector.

52. The method of claim 47 wherein the constrained input solution to the mathematical model is constrained by at least one operational limitation related to patient safety or comfort.

53. The method of claim 47 wherein the injection of the contrast medium is commenced at one time and an image scan of the region of interest is commenced at a second time determined at least in part on the basis of the mathematical model.

54. The method of claim 53 wherein the second time is determined on the basis of a prediction of a time of attainment of a predetermined enhancement level as determined by the mathematical model.

55. The method of claim 47 wherein the at least one mathematical model is a patient transfer function for the patient based upon data specific to the patient, the at least one patient transfer function providing a time enhancement output for a given input.

56. The method of claim 55 wherein the patient transfer function is determined using a system identification model comprising parameters related to physiological parameters of the patient or is determined using a mathematic identification model determined by collecting data corresponding to a time enhancement curve resulting from the injection of the patient, wherein the mathematical identification model describes the data.

57. A method of controlling injection of a pharmaceutical fluid into a patient using an injector having a controller in communicative connection with a computer memory in a medical procedure, comprising:

(a) collecting data corresponding to a patient response curve resulting from an injection of the pharmaceutical fluid;

(b) choosing at least one mathematical model from a plurality of mathematical models stored in the computer memory to describe the data;

(c) adapting the at least one mathematical model to the collected data; and

(d) controlling the injector via the controller during the medical procedure to control the injection of the pharmaceutical fluid into the patient to create a patient response at least in part on the basis of the at least one mathematical model.

58. An imaging system, comprising:

(a) an imager to create an image of a region of interest of a patient;

(b) an injector adapted to inject a contrast medium; and

(c) a controller in operative communication with the injector to control the injector, the controller comprising;

(I) at least one patient transfer function determined for the patient based upon data specific to the patient, the at least one patient transfer function providing a time enhancement output for a given input, the data specific to the patient including at least one of an estimate of physiologic parameters of the patient, an estimate of anatomic parameters of the patient and an enhancement caused by an injection of the contrast medium into the patient; and

(II) a processor to determine an injection procedure input for a desired time enhancement output using the at least one patient transfer function.