Methods and systems for assessing healing of tissue

1. A system for allowing assessment of tissue of a subject, the system comprising:

one or more processors; and

memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to:

receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region;

determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue.

2. The system of claim 1 , wherein at least one calculation region is defined by one pixel or one voxel.

3. The system of claim 1 , wherein the coefficient value characterizes a shape of the time-intensity curve.

4. The system of claim 3 , wherein the coefficient value characterizes a region of increasing slope of the time-intensity curve, a region of decreasing slope of the time-intensity curve, or a combination thereof.

5. The system of claim 4 , wherein the region of increasing slope of the time-intensity curve represents an arterial phase of the time-intensity curve and the region of decreasing slope of the time-intensity curve represents a venous phase of the time-intensity curve.

6. The system of claim 1 , wherein the coefficient-derived image map is based on a correlation of each of the coefficient values with a respective pixel intensity.

7. The system of claim 1 , wherein the coefficient-derived image map allows for, or provides information for use in, predictive assessment of healing of tissue of the subject.

8. The system of claim 1 , further comprising a display, wherein the instructions cause the system to display the coefficient-derived image map on the display.

9. The system of claim 8 , wherein the instructions cause the system to superimpose the coefficient-derived image map on an anatomical image of the tissue on the display.

10. The system of claim 1 , further comprising (i) a light source that provides an excitation light to induce fluorescence emission from the imaging agent in the tissue; (ii) an image acquisition assembly that generates the time series of signal intensity data based on the fluorescence emission, (iii) or a combination thereof.

11. The system of claim 1 , wherein the tissue comprises non-wound tissue, wound tissue, or a combination thereof.

12. A method for use in medical imaging for assessing tissue of a subject, the method comprising:

at a computer system including one or more processors and memory,

receiving a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region;

determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue.

13. The method of claim 12 , wherein at least one calculation region is defined by one pixel or one voxel.

14. The method of claim 12 , wherein the coefficient value characterizes a shape of the time-intensity curve.

15. The method of claim 14 , wherein the coefficient value characterizes a region of increasing slope of the time-intensity curve, a region of decreasing slope of the time-intensity curve, or a combination thereof.

16. The method of claim 15 , wherein the region of increasing slope of the time-intensity curve represents an arterial phase of the time-intensity curve and the region of decreasing slope of the time-intensity curve represents a venous phase of the time-intensity curve.

17. The method of claim 12 , wherein converting the coefficient values into a coefficient-derived image map comprises correlating each coefficient value with an intensity value.

18. The method of claim 12 , further comprising displaying the coefficient-derived image map on a display.

19. The method of claim 18 , further comprising superimposing the coefficient-derived image map on an anatomical image of the tissue on the display.

20. The method of claim 12 , wherein the assessing of tissue of the subject is based at least in part on the coefficient-derived image map.

21. The method of claim 20 , wherein the assessing of tissue of the subject comprises assessing a wound in the tissue, a peri-wound in the tissue, or a combination thereof.

22. The method of claim 21 , wherein assessing the wound in the tissue, the peri-wound in the tissue, or the combination thereof comprises assessing a state of the tissue, a property of the tissue, a condition of the tissue, a healing status of the tissue, or a combination thereof.

23. The method of claim 20 , wherein the assessing of tissue of the subject comprises assessing a healing status of a wound based on a heterogeneous pattern in the coefficient-derived image map.

24. The method of claim 20 , wherein the assessing of tissue of the subject comprises generating a quantitative predictor of the progress of healing of tissue, efficacy of clinical intervention, or a combination thereof, based on at least a portion of the coefficient-derived image.

25. The method of claim 20 , further comprising comparing a plurality of coefficient-derived image maps that are based on a plurality of time series of signal intensity data captured over time, and assessing progress of healing of tissue, efficacy of clinical intervention, or a combination thereof based on the comparison of the plurality of coefficient-derived image maps.

26. The method of claim 20 , further comprising:

determining, for each calculation region, a second coefficient value that is related to at least a second portion of the time-intensity curve corresponding to the calculation region; and

converting the second coefficient values across the plurality of calculation regions into a second coefficient-derived image map.

27. The method of claim 26 , wherein the first coefficient-derived image map is an arterial coefficient-derived image map and the second coefficient-derived image map is a venous coefficient-derived image map.

28. The method of claim 26 , wherein the assessing of tissue of the subject comprises generating a quantitative predictor of the progress of healing of tissue, efficacy of clinical intervention, or a combination thereof, based on the first and second coefficient-derived image maps.

29. The method of claim 28 , wherein generating a quantitative predictor comprises comparing the area of a first selected region in the first coefficient-derived image map to the area of a second selected region in the second coefficient-derived image map.

30. The method of claim 29 , wherein the first and second selected regions represent an actual or suspected wound.

31. The method of claim 29 , wherein comparing the area of the first selected region and the area of the second selected region comprises determining a ratio of the area of the first selected region and the second selected region.

32. The method of claim 12 , further comprising generating the time series of signal intensity data using a fluorescence imaging system that captures transit of the imaging agent through tissue over a period of time.

33. The method of claim 12 , wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof.

34. A kit comprising the system of claim 1 and an imaging agent.

35. The kit of claim 34 , wherein the imaging agent comprises a fluorescence imaging agent.

36. The kit of claim 35 , wherein the fluorescence imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof.

37. The kit of claim 34 further comprising a tangible non-transitory computer readable medium having computer-executable program code embedded thereon, the computer executable program code providing instructions for causing one or more processors, when executing the instructions, to perform the method of receiving a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region;

determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map.

38. The kit of claim 37 further comprising instructions for installing the computer-executable program code.

39. A method for visualizing transit of an imaging agent through tissue of a subject, the method comprising:

at a computer system including one or more processors and memory,

receiving a time series of signal intensity data capturing the transit of the imaging agent through the tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region;

determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue.

40. The method of claim 39 , wherein at least one calculation region is defined by one pixel or one voxel.

41. The method of claim 39 , wherein the coefficient value characterizes a shape of the time-intensity curve.

42. The method of claim 41 , wherein the coefficient value characterizes a region of increasing slope of the time-intensity curve, a region of decreasing slope of the time-intensity curve, or a combination thereof.

43. The method of claim 39 , further comprising displaying the coefficient-derived image map on a display.

44. The method of claim 43 , wherein the coefficient-derived image map is a still image.

45. The method of claim 43 , further comprising superimposing the coefficient-derived image map on an anatomical image of the tissue on the display.

46. A system for allowing assessment of tissue of a subject, the system comprising:

one or more processors; and

memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to:

receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region;

determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein a heterogeneous pattern in the coefficient-derived image map is indicative of an actual or suspected wound.

47. A system for allowing assessment of tissue of a subject, the system comprising:

one or more processors; and

memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to:

receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region;

determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein the assessing of tissue of the subject is based at least in part on the coefficient-derived image map; and

wherein the assessing of tissue of the subject comprises assessing a wound in the tissue, a peri-wound in the tissue, or a combination thereof.

48. A kit comprising:

a system for allowing assessment of tissue of a subject, the system comprising:

one or more processors; and

memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to:

receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region;

determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map; and

an imaging agent, wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof.

49. A method for use in medical imaging for assessing tissue of a subject, the method comprising:

administering an imaging agent to the subject;

at a computer system including one or more processors and memory,

receiving a time series of signal intensity data capturing transit of the imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region;

determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue.

50. The method of claim 49 , wherein the tissue comprises non-wound tissue, wound tissue, or a combination thereof.

51. The method of claim 49 , wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof.

52. The method of claim 49 , wherein the imaging agent comprises indocyanine green.

53. A method for visualizing transit of an imaging agent through tissue of a subject, the method comprising:

administering the imaging agent to the subject;

at a computer system including one or more processors and memory,

receiving a time series of signal intensity data capturing the transit of the imaging agent through the tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region;

determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and

converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map;

wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue.

54. The method of claim 53 , wherein the tissue comprises non-wound tissue, wound tissue, or a combination thereof.

55. The method of claim 53 , wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof.

56. The method of claim 53 , wherein the imaging agent comprises indocyanine green.