Methods and systems for providing planning and dispensation of research and/or treatment for brain disease

• US 9,265,577 B2
• Filed: 05/07/2008
• Issued: 02/23/2016
• Est. Priority Date: 05/18/2007
• Status: Expired due to Fees

• Current Assignee: Johns Hopkins University, Therataxis, LLC
• Original Assignee: Johns Hopkins University
• Inventors: Raghavan, Raghu, Grossman, Stuart A.
• Primary Examiner(s): FERNANDEZ, KATHERINE L
• Application Number:
  US12/116,765
• Publication Number:
  US 20090024181A1
• Time in Patent Office: 2,848 Days
• Field of Search: 600/407, 600/410, 600/416, 600419-420, 382/128
• US Class Current: 1/1
• CPC Class Codes: A61B 2034/101 Computer-aided simulation of surgical operations
• CPC Class Codes: A61B 2034/252 indicating steps of a surgical procedure
• CPC Class Codes: A61B 34/10 Computer-aided planning, simulation or modelling of surgical operations
• CPC Class Codes: A61B 6/461 Displaying means of special interest
• CPC Class Codes: A61B 6/481 involving the use of contrast agents
• CPC Class Codes: A61B 6/501 for diagnosis of the head, e.g. neuroimaging or craniography
• CPC Class Codes: A61B 90/00 Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges protective face masks A41D13/11; surgeon's or patient's gowns or dresses A41D13/12; devices for carrying-off, for treatment of, or for carrying-over, body liquids A61M1/00
• CPC Class Codes: A61N 2005/1021 Radioactive fluid
• CPC Class Codes: G06T 2207/30016 Brain
• CPC Class Codes: G06T 7/0012 Biomedical image inspection
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 30/20 for handling medical images, e.g. DICOM, HL7 or PACS
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Methods and systems for providing planning and dispensation of research and/or treatment for brain disease. Radiological information is generated in a region of interest in an area of the a brain of an individual using a radiological imaging system. A physiological states model is constructed which assesses physiological states of the region of interest. Locations of sources of interstitial fluid flow, fluid conductivities of paths, and anatomical information in the region of interest are obtained using the radiological imaging information. Velocities of the interstitial fluid flow in the region of interest are computed using the physiological states model, the locations of sources of interstitial flow, the fluid conductivities, and the anatomic information. A model of the area of the brain is created, the model including the region of interest.

Claims

1. A method for providing planning and dispensation of research and/or treatment for brain disease, comprising:

generating radiological information in a region of interest in an area of the a brain of an individual using a radiological imaging system, the region of interest comprising a pathological lesion associated with the brain disease and an area outside the pathological lesion;

constructing, using a computer, a physiological states model which assesses physiological states of the region of interest;

obtaining, using the computer, locations of sources of interstitial fluid flow, fluid conductivities of paths, and anatomical information in the region of interest using the radiological imaging information;

computing, using the computer, velocities of the interstitial fluid flow in the region of interest using the physiological states model, the locations of sources of interstitial flow, the fluid conductivities, and the anatomic information, wherein said computing takes into account changes in interstitial fluid flow caused by the pathological lesion;

creating, using the computer, a model of the area of the brain including the region of interest, wherein said model shows the computed velocities of the interstitial flow and interstitial pressure variations in the interstitial fluid changed due to the pathological lesion, within and outside the lesion in the region of interest; and

displaying the model for the planning and the dispensation of research and/or treatment for brain disease.

2. The method of claim 1, wherein the anatomical information comprises:

information regarding major fiber tracts in a brain;

information regarding a cerebral cortex;

information regarding blood vessels in the brain;

information regarding cells in the brain; and

/or information regarding cerebral spinal fluid regions in the brain.

3. The method, of claim 1, wherein the physiological states model is constructed utilizing the anatomical information.

4. The method of claim 1, wherein a strength of the sources is determined.

5. The method of claim 1, further comprising:

injecting a substance which can be imaged into a brain;

obtaining estimates of velocities of flow and interstitial pressure variations based on movement of an introduced substance in the brain; and

creating an updated model of the area of the brain outside the pathologic lesion based on the estimates obtained from the introduced substance.

6. The method of claim 5, wherein the injected substance is not injected in brain tissue.

7. The method of claim 5, wherein the injected substance is injected in blood vessels.

8. The method of claim 1, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the method further comprises:

analyzing a radiological image for a brain of a particular patient; and

creating a patient specific flow model utilizing the model of the area of the brain outside the pathological lesion and radiological imaging of the brain of the particular patient.

9. The method of claim 8, further comprising:

analyzing radiological imaging recurrence data as a disease progresses; and

creating an updated patient specific flow model utilizing the patient specific flow model and the radiological imaging recurrence data.

10. The method of claim 8, further comprising:

obtaining a radiation therapy plan;

determining if the radiation therapy plan covers significant predicted recurrence zones utilizing the patient specific flow model and the radiation therapy plan, and

if the radiation therapy plan covers significant predicted recurrence zones, proceeding with the radiation therapy plan.

11. The method of claim 10, further comprising:

if the radiation therapy plan does not cover predicted recurrence zones, determining if any recurrence zones are in radiation resistant matter; and

if any recurrence zones are in radiation resistant matter, creating an updated therapy plan which accounts for the recurrence zones in the radiation resistant matter.

12. The method of claim 11, wherein the updated therapy plan includes:

an updated radiation therapy plan;

a surgery plan; and

/or

a drug delivery plan.

13. The method of claim 11, further comprising:

if the recurrence zones are not in the radiation resistant matter, determining if any recurrence zones are in vital tissue; and

if any recurrence zones are in vital tissue, creating an updated therapy plan which accounts for the recurrence zones in the vital tissue.

14. The method of claim 13, wherein the updated therapy plan includes:

an updated radiation therapy plan;

a surgery plan; and

/or

a drug delivery plan.

15. The method of claim 13, further comprising:

if none of the recurrence zones are in vital tissue, creating an updated radiation therapy plan which expands the recurrence zones and/or augments a planned dose.

16. The method of claim 15, wherein the model of the area of the brain in the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the physiological model, an interstitial model, and a model of the area of the brain outside the pathological lesion are made under normal or diseased conditions.

17. The method of claim 16, wherein the diseased conditions comprise a primary brain tumor and/or Alzheimer'"'"'s disease with deposition of plaque.

18. The method of claim 8, further comprising:

obtaining a surgical resection plan;

determining if the surgical resection plan covers significant predicted recurrence zones utilizing the patient specific flow model and the surgical resection plan; and

if the surgical resection plan covers significant predicted recurrence zones, proceeding with the surgical resection plan.

19. The method of claim 18, further comprising:

if the surgical resection plan does not cover significant predicted recurrence zones, determining if recurrence is widespread, and

if the recurrence is widespread, creating an updated surgical resection plan based on the widespread recurrence.

20. The method of claim 19, further comprising:

if the recurrence is not widespread, creating an updated surgical resection plan including more aggressive surgery.

21. The method of claim 1, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and the method further comprising:

obtaining a cell movement model of a brain;

obtaining a stem cell migration model of the brain utilizing the model of the area of the brain outside the pathological lesion and the cell movement model;

analyzing radiological imaging of the brain of a particular patient; and

creating a patient specific cell migration model of the patient'"'"'s brain utilizing the model of the area of the brain outside the pathological lesion and the radiological imaging of the brain of the particular patient.

22. The method of claim 1, further comprising:

creating a trans-capillary exchange model which estimates where and how easily chemotherapy molecular material moves in and out of a brain utilizing the physiological states model; and

creating a chemotherapy delivery model utilizing the trans-capillary exchange model.

23. The method of claim 22, further comprising:

injecting a substance which can be imaged into the brain;

obtaining estimates of chemotherapeutic delivery based on the movement of the introduced substance in the brain; and

obtaining an updated chemotherapy delivery model based on the estimates obtained from the introduced substance.

24. The method of claim 23, further comprising:

obtaining a radiation therapy plan;

selecting perfusion imaging to quantify altered blood brain barrier permeabilities;

obtaining a chemotherapy delivery model;

analyzing radiological imaging of the brain of a particular patient; and

creating a patient specific cell migration model of the patient'"'"'s brain utilizing the radiation therapy plan, the selected perfusion imaging, the chemotherapy delivery model, and the radiological imaging of the brain of the particular patient.

25. The method of claim 22, further comprising:

analyzing radiological imaging of the brain of a particular patient; and

creating predictions regarding functional capillary density, capillary perfusion, disruption of the blood-brain barrier and molecular permeability, and/or intracerebral pressure utilizing the model of the area of the brain outside the pathological lesion, the chemotherapy delivery model, and the radiological imaging of the brain of the particular patient.

26. The method of claim 1, wherein the individual is an animal and/or a human.

27. The method of claim 1, where the radiological imaging information comprises magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic contrast-enhanced imaging (DCE), and/or arterial spin labeling (ASL).

28. The method of claim 27, wherein the ASL is with magnetization transfer imaging (MTI).

29. The method of claim 1, wherein the physiological states model comprises a mathematical model of transport of hydrophilic plasma proteins across the blood vessel.

30. The method of claim 1, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the model of the area of the brain outside the pathological lesion accounts for:

variations in hydrophilic proteins in an interstitium of a brain of a living patient;

variations in interstitial pressure in the brain of the living patient;

likely sites of recurrence of a primary brain tumor cells;

mapping migration of the primary brain tumor cells;

mapping extracellular fluid pathways in the brain relevant for deposition of amyloid plaque in Alzheimer'"'"'s disease;

or

planning therapy to dissolve the deposited plaque;

or

any combination thereof.

31. The method of claim 1, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the radiological imaging information is specialized to delineate Virchow-Robin spaces and the model of the area of the brain outside the pathological lesion is used to predict likely migration and deposition sites for coagulated proteins manufactured by diseased cortical neurons.

32. The method of claim 1, further comprising:

obtaining drug characteristics of a drug and ex-vivo prior data for the individual;

obtaining pharmacokinetic model utilizing drug characteristics and ex-vivo prior data;

obtaining an estimate of systemic concentration of the drug utilizing a pharmacokinetic model;

transmitting the drug into a central nervous system (CNS);

determining if an adequate dose of the drug was used for testing;

if the dose was adequate for testing, obtain spatial patterning of kinetics of the drug in-vivo; and

obtain efficacious drug delivery, testing, and/or monitoring protocols for CNS pharmaceuticals.

33. The method of claim 32, further comprising:

if the dose was not adequate for testing, modifying the delivery plan by taking into account a pharmaceutical drug delivery plan and a chemotherapy delivery model.

34. The method of claim 1, further comprising obtaining particulate material flow and distribution in the region of interest using the physiological states model.

35. The method of claim 34, wherein particulate material is:

cellular material;

molecular material; and

/or

viral material.

36. The method of claim 35, further comprising:

determining likely plaque migration pathways and/or deposition sites utilizing a patient specific flow model; and

determining requirements for delivery of plaque dissolution agents.

37. The method of claim 1, further comprising obtaining the pressure variations in the region of interest using the physiological states model.

73. The system of claim 34, wherein the computer is further configured to obtain particulate material flow and distribution in the region of interest using the physiological states model.

74. The system of claim 73, wherein the particulate material is:

cellular material;

molecular material; and

/or

viral material.

75. The system of claim 74, wherein the computer is further configured to:

determine likely plaque migration pathways and/or deposition sites utilizing the patient specific flow model; and

determine requirements for delivery of plaque dissolution agents.

38. A system for providing planning and dispensation of research and/or treatment for brain disease, comprising:

a radiological imaging system configured to generate radiological information in a region of interest in an area of a brain of an individual, the region of interest comprising a pathological lesion associated with the brain disease and an area outside the pathological lesion;

a computer having an application stored therein for causing the computer to;

receive the radiological information;

construct a physiological states model which assesses physiological states of the region of interest;

obtain locations of sources of interstitial fluid flow, fluid conductivities of paths, and anatomical information in the region of interest using the radiological imaging information;

compute velocities of the interstitial fluid flow in the region of interest using the physiological states model, the locations of sources of interstitial flow, the fluid conductivities, and the anatomical information, wherein the computing takes into account changes in interstitial fluid flow caused by the pathological lesion; and

create a model of the area of the brain including the region of interest, wherein said model shows the computed velocities of the interstitial flow and interstitial pressure variations in the interstitial fluid changed due to the pathological lesion, within and outside the lesion in the region of interest; and

a display for displaying the model for the planning and the dispensation of research and/or treatment for brain disease.

39. The system of claim 38, wherein the anatomical information comprises:

information regarding major fiber tracts in a brain;

information regarding a cerebral cortex;

information regarding blood vessels in the brain;

information regarding cells in the brain; and

/or information regarding cerebral spinal fluid regions in the brain.

40. The system of claim 38, wherein the physiological states model is constructed utilizing the anatomical information.

41. The system of claim 38, wherein a strength of the sources is determined.

42. The system of claim 38, wherein the computer is further configured to:

obtain estimates of velocities of flow and interstitial pressure variations based on movement of an introduced substance in the brain, wherein the introduced substance is able to be imaged; and

create an updated model of the area of the brain outside the pathologic lesion based on the estimates obtained from the introduced substance.

43. The system of claim 38, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the computer is further configured to:

analyze radiological imaging of a brain of a particular patient; and

create a patient specific flow model utilizing the model of the area of the brain outside the pathological lesion and the radiological imaging of the brain of the particular patient.

44. The system of claim 43, wherein the computer is further configured to:

analyze radiological imaging recurrence data as a disease progresses; and

create an updated patient specific flow model utilizing the patient specific flow model and the radiological imaging recurrence data.

45. The system of claim 43, wherein the computer is further configured to:

obtain a radiation therapy plan;

determine if the radiation therapy plan covers predicted recurrence zones utilizing the patient specific flow model and the radiation therapy plan, and

if the radiation therapy plan covers significant predicted recurrence zones, proceeding with the radiation therapy plan.

46. The system of claim 45, wherein the computer is further configured to:

if the radiation therapy plan does not cover significant predicted recurrence zones, determine if any recurrence zones are in radiation resistant matter; and

if any recurrence zones are in radiation resistant matter, create an updated therapy plan which accounts for the recurrence zones in the radiation resistant matter.

47. The system of claim 46, wherein the updated therapy plan includes:

an updated radiation therapy plan;

a surgery plan; and

/or

a drug delivery plan.

48. The system of claim 47, wherein the computer is further configured to:

if the recurrence zones are not in the radiation resistant matter, determine if any recurrence zones are in vital tissue; and

if any recurrence zones are in vital tissue, create an updated therapy plan which accounts for the recurrence zones in the vital tissue.

49. The system of claim 48, wherein the computer is further configured to:

if none of the recurrence zones are in vital tissue, create an updated radiation therapy plan which expands the recurrence zones and/or augments a planned dose.

50. The system of claim 49, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the physiological model, an interstitial model, and the model of the area of the brain outside the pathological lesion are made under normal or diseased conditions.

51. The system of claim 50, wherein the diseased conditions comprise:

a primary brain tumor and/or Alzheimer'"'"'s disease with deposition of plaque.

52. The system of claim 47, wherein the updated therapy plan includes:

an updated radiation therapy plan;

a surgery plan; and

/or

a drug delivery plan.

53. The system of claim 43, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein computer is further configured to:

obtain a surgical resection plan;

determine if the surgical resection plan covers significant predicted recurrence zones utilizing the patient specific flow model and the surgical resection plan; and

if the surgical resection plan covers significant predicted recurrence zones, proceeding with the surgical resection plan.

54. The system of claim 53, wherein the computer is further configured to:

if the surgical resection plan does not cover significant predicted recurrence zones, determine if recurrence is widespread; and

if the recurrence is widespread, create an updated surgical resection plan based on the widespread recurrence.

55. The system of claim 54, wherein the computer is further configured to:

if the recurrence is not widespread, create an updated surgical resection plan including more aggressive surgery.

56. The system of claim 38, wherein the computer is further configured to:

obtain a cell movement model of a brain;

obtain a stem cell migration model of the brain utilizing the model of the area of the brain outside the pathological lesion and the cell movement model;

analyze radiological imaging of the brain of a particular patient; and

create a patient specific cell migration model of the patient'"'"'s brain utilizing the model of the area of the brain outside the pathological lesion and the radiological imaging of the brain of the particular patient.

57. The system of claim 38, wherein the computer is further configured to:

create a trans-capillary exchange model which estimates where and how easily chemotherapy molecular material moves in and out of a brain utilizing the physiological states model; and

create a chemotherapy delivery model utilizing the trans-capillary exchange model.

58. The system of claim 57, wherein the computer is further configured to:

analyze radiological imaging of the brain of a particular patient; and

create predictions regarding functional capillary density, capillary perfusion, disruption of the blood-brain barrier and molecular permeability, and/or intracerebral pressure utilizing the model of the area of the brain outside the pathologic lesion, the chemotherapy delivery model, and the radiological imaging of the brain of the particular patient.

59. The system of claim 38, wherein the computer is further configured to:

obtain estimates of chemotherapeutic delivery based on a movement of an introduced substance in the brain; and

obtaining an updated chemotherapy delivery model based on the estimates obtained from the introduced substance.

60. The system of claim 59, wherein the computer is further configured to:

obtain a radiation therapy plan;

select perfusion imaging to quantify altered blood brain barrier permeabilities;

obtain a chemotherapy delivery model;

analyze radiological imaging of the brain of a particular patient; and

create a patient specific cell migration model of the patient'"'"'s brain utilizing the radiation therapy plan, the selected perfusion imaging, the chemotherapy delivery model, and the radiological imaging of the brain of the particular patient.

61. The system of claim 38, wherein the individual is an animal and/or a human.

62. The system of claim 38, where the radiological imaging information comprises magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic contrast enhanced imaging (DCE), and/or arterial spin labeling (ASL).

63. The system of claim 62, wherein the ASL is with magnetization transfer imaging (MTI).

64. The system of claim 38, wherein the physiological states model comprises a mathematical model of transport of hydrophilic plasma proteins across the blood vessel.

65. The system of claim 38, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the model of the area of the brain outside the pathological lesion accounts for:

variations in hydrophilic proteins in an interstitium of a brain of a living patient;

variations in the interstitial pressure in the brain of the living patient;

mapping migration of a primary brain tumor cells;

likely sites of recurrence of the primary brain tumor cells;

mapping extracellular fluid pathways in the brain relevant for the deposition of amyloid plaque in Alzheimer'"'"'s disease;

or

planning therapy to dissolve the deposited plaque;

or

any combination thereof.

66. The system of claim 38, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the radiological imaging is specialized to delineate Virchow-Robin spaces and the model of the area of the brain outside the pathological lesion is used to predict likely migration and deposition sites for coagulated proteins manufactured by diseased cortical neurons.

67. The system of claim 38, wherein the computer is further configured to:

obtain drug characteristics of a drug and ex-vivo prior data for the individual;

obtain pharmacokinetic model utilizing drug characteristics and ex-vivo prior data;

obtain an estimate of systemic concentration of the drug utilizing a pharmacokinetic model;

transmit the drug into a central nervous system (CNS);

determine if an adequate dose of the drug was used for testing;

if the dose was adequate for testing, obtain spatial patterning of kinetics of the drug in-vivo; and

obtain efficacious drug delivery, testing, and/or monitoring protocols for CNS pharmaceuticals.

68. The system of claim 67, wherein the computer is further configured to:

if the dose was not adequate for testing, modify the delivery plan by taking into account a pharmaceutical drug delivery plan and a chemotherapy delivery model.

69. The system of claim 38, wherein the model of the area of the brain including the region of interest comprises a model of the area of the brain outside the pathological lesion, and wherein the display comprises a user interface to display the model of the area of the brain outside the pathological lesion.

70. The system of claim 38, wherein the display comprises:

a user interface configured to accept information utilized by the application and display information generated by the application.

71. The system of claim 38, wherein the radiological imaging is obtained from a magnetic resonance imaging apparatus capable of:

obtain high resolution T2-weighted imaging; and

/or

control diffusion times and gradient strengths in diffusion weighted imaging.

72. The system of claim 38, wherein the sources and/or directions of interstitial flow are obtained by:

intravenous application of manganese chloride or other contrast reagents for radiological imaging; and

/or

depositing or injecting nanoparticles in brain parenchyma.

76. The system of claim 38, wherein the computer is further configured to obtain pressure variations in the region of interest using the physiological states model.