Methods, systems and computer program products for non-invasive determination of blood flow distribution using speckle imaging techniques and hemodynamic modeling

• US 9,271,658 B2
• Filed: 01/09/2012
• Issued: 03/01/2016
• Est. Priority Date: 01/10/2011
• Status: Active Grant

• Current Assignee: East Carolina University
• Original Assignee: East Carolina University
• Inventors: Ferguson, Thomas Bruce Jr., Hu, Xin-Hua, Chen, Cheng
• Primary Examiner(s): YANG, WEI WEN
• Application Number:
  US13/819,817
• Publication Number:
  US 20130223705A1
• Time in Patent Office: 1,513 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: G02B 27/48 Laser speckle optics
• CPC Class Codes: G06T 7/0012 Biomedical image inspection

Abstract

A non-invasive method for measuring blood flow in principal vessels of a heart of a subject is provided. The method includes illuminating a region of interest in the heart with a coherent light source, wherein the coherent light source has a wavelength of from about 600 nm to about 1100 nm; sequentially acquiring at least two speckle images of the region of interest in the heart during a fixed time period, wherein sequentially acquiring the at least two speckle images comprises acquiring the at least two speckle images in synchronization with motion of the heart of the subject; and electronically processing the at least two acquired speckle images based on the temporal variation of the pixel intensities in the at least two acquired speckle images to generate a laser speckle contrast imaging (LSCI) image and determine spatial distribution of blood flow rate in the principal vessels and quantify perfusion distribution in tissue in the region of interest in the heart from the LSCI image.

Claims

1. A non-invasive method for measuring blood flow distribution in principal vessels of a heart of a subject, the method comprising:

passively illuminating a region of interest in the heart with a coherent light source, wherein the coherent light source has a wavelength of from about 600 nm to about 1100 nm and a field of view including the region of interest is at least about 2 square centimeters;

sequentially acquiring at least two speckle images of the region of interest in the heart during a fixed time period, wherein sequentially acquiring the at least two speckle images comprises acquiring the at least two speckle images in synchronization with motion of the heart of the subject and the acquisition being triggered by the motion of the heart of the subject; and

electronically processing the at least two acquired speckle images based on the temporal variation of the pixel intensities in the at least two acquired speckle images to generate a laser speckle contrast imaging (LSCI) image and determine spatial distribution of blood flow speed in the principal vessels and quantify perfusion distribution in tissue in the region of interest in the heart from the LSCI image.

2. The method of claim 1, wherein sequentially acquiring the at least two speckle images in synchronization with motion of the heart of the subject further comprises:

electronically monitoring an EKG cardiac cycle of the subject to identify a pattern in the EKG cardiac cycle that differentiates between at least systolic and diastolic phases; and

electronically synchronizing acquisition of speckle images with the EKG signals.

3. The method of claim 1, wherein the sequentially acquiring and the electronically evaluating are performed before a procedure performed on a subject and after the procedure performed on the subject, the method further comprising:

comparing the determined blood flow speed in the principal vessels and perfusion distribution in tissue in the region of interest in the heart before the procedure with the determined blood flow speed in the principal vessels and perfusion distribution in tissue in the region of interest in the heart after the procedure to access success of the procedure.

4. The method of claim 1, further comprising:

quantification of tissue perfusion by calculating blood flow rate distribution in the region of interest in the heart based on a calculated velocity field; and

comparing the calculated blood flows speed in the region of interest to the blood flow speed determined using the acquired at least two speckle images of the region of interest in the heart to verify results obtained using the at least two speckle images.

5. The method of claim 4, wherein the fields of velocity and flow rate are calculated based on the following equations with appropriate boundary and initial conditions:

6. The method of claim 1, wherein the coherent light source has a wavelength of from about 600 nm to about 1100 nm and allows relatively deep penetration of light into tissues to thereby allow an accurate determination of blood flow speed in the principal vessels and the perfusion distribution under surface.

7. The method of claim 1, wherein the coherent light source comprises a laser configured to illuminate the region of interest with a substantially constant intensity.

8. The method of claim 7, wherein the laser has a fixed or variable wavelength of from about 600 nm to about 1100 nm.

9. The method of claim 7, wherein the laser generates an output beam having a substantially constant intensity within a field-of-view (FOV) of an imaging unit.

10. The method of claim 7, wherein the laser comprises a low power and continuous-wave laser such that the subject does not require any protective apparatus to shield the subject from effects of the laser.

11. The method of claim 7, wherein the laser produces a single beam of light of a wavelength within a spectral region from the ultraviolet to the infrared.

12. The method of claim 11, wherein the sequentially acquiring comprises sequentially acquiring from about 50 to about 1000 speckle images using the camera during the fixed time period of from about 1 ms to about 200 ms.

13. The method of claim 12, wherein sequentially acquiring comprises acquiring from about 200 to about 500 speckle images during the fixed time period.

14. The method of claim 11, wherein the fixed time period is selected based on in situ acquisition of blood flow speed of the subject in the region of interest.

35. The method of claim 1, wherein sequentially acquiring the at least two speckle images comprises:

triggering acquisition of the at least two speckle images with the motion of the heart of the subject; and

synchronizing in real time the triggered acquisition of the at least two speckle images with the motion of the heart of the subject.

36. The method of claim 35, wherein triggering further comprises recognizing a pattern in the motion of the heart of the subject and differentiating between diastolic and systolic phases of the heart.

37. The method of claim 1, wherein acquiring the at least two speckle images in synchronization with motion of the heart of the subject further comprises:

calculating a surrogate EKG signal from acquired images at different phases of a cardiac cycle; and

electronically synchronizing acquisition of speckle images with the surrogate EKG signal.

38. The method of claim 1, wherein the motion of the heart comprises physical motion of the heart.

15. A non-invasive method for measuring blood flow distribution in principal vessels of a subject, the method comprising:

passively illuminating a region of interest with a coherent light source, wherein the coherent light source has a wavelength of from about 600 nm to about 1100 nm and a field of view including the region of interest is at least about 2 square centimeters;

sequentially acquiring at least two speckle images of the region of interest during a fixed time period;

electronically processing the at least two acquired speckle images based on the temporal variation of the pixel intensities in the at least two acquired speckle images to generate a laser speckle contrast imaging (LSCI) image and determine spatial distribution of blood flow speed in the principal vessels and quantify perfusion distribution in tissue in the region of interest from the LSCI image;

calculating a velocity field for the region of interest;

calculating blood flow rate distribution in the region of interest based on the calculated velocity field; and

comparing the calculated blood flow speed in the region of interest to the blood flow speed determined using the acquired at least two speckle images of the region of interest to verify results obtained using the at least two speckle images.

16. The method of claim 15, wherein the fields of velocity and flow rate are calculated based on the following equations with appropriate boundary and initial conditions:

17. The method of claim 16, wherein the sequentially acquiring, the electronically evaluating, calculating the velocity field, calculating the blood flow rate based on the calculated velocity field and the comparing are performed before a procedure performed on a subject and after the procedure performed on the subject, the method further comprising comparing the results before and after the procedure to access success of the procedure.

18. A non-invasive system for measuring blood flow distribution in principal vessels in a heart of a subject, the system comprising:

a coherent light source configured to passively illuminate a region of interest in the heart of the subject, the coherent light source having a wavelength of from about 600 nm to about 1100 and a field of view including the region of interest is at least about 2 square centimeters;

a camera in communication with the coherent light source that is configured to sequentially acquire at least two speckle images of the region of interest in the heart during a fixed time period, wherein acquisition of the at least two speckle images is synchronized with and trigger by motion of the heart of the subject; and

a data processing circuit configured to evaluate the temporal variation of the pixel intensities in the at least two acquired speckle images to generate a laser speckle contrast imaging (LSCI) image and determine spatial distribution of blood flow speed in the principal vessels and quantify perfusion distribution in tissue in the region of interest in the heart from the LSCI image.

19. The system of claim 18, wherein the data processing circuit is further configured to:

electronically monitor an EKG cardiac cycle of the subject to identify a pattern in the EKG cardiac cycle that differentiates between at least systolic and diastolic phases; and

electronically synchronize acquisition of speckle images with the EKG signals.

20. The system of claim 18, further comprising a modeling module configured to:

calculate a velocity field for the region of interest in the heart;

calculate blood flow rate in the region of interest in the heart based on the calculated velocity field; and

compare the calculated blood flow in the region of interest to the blood flow speed determined using the acquired at least two speckle images of the region of interest in the heart to verify results obtained using the at least two speckle images.

21. The system of claim 20, wherein modeling module is configured to calculate the fields of velocity and rate based on the following equations with appropriate boundary and initial conditions:

22. The system of claim 18, wherein the coherent light source has a wavelength of from about 600 nm to about 1100 nm and is configured to allow deep penetration of light into tissues and to provide an accurate determination of blood flow speed in the principal vessels and the perfusion distribution under surface.

23. The system of claim 18, wherein the coherent light source comprises a laser configured to illuminate the region of interest with a substantially constant intensity.

24. The system of claim 23, wherein the laser has a fixed or variable wavelength of from about 600 nm to about 1100 nm.

25. The system of claim 23, wherein the laser is configured to illuminate the region of interest with a laser beam having substantially constant intensity within a field-of-view (FOV) of an imaging unit.

26. The system of claim 23, wherein the laser comprises a low power and continuous-wave laser such that the subject does not require any protective apparatus to shield the subject from effects of the laser.

27. The system of claim 23, wherein the laser is configured to produce a single beam of light in a wavelength within a spectral region from the ultraviolet to the infrared.

28. The system of claim 18, wherein the camera is configured to acquire from about 50 to about 1000 speckle images during the fixed time period of from about 1 ms to about 200 ms.

29. The system of claim 28, wherein the camera is configured to acquire from about 200 to about 500 speckle images during the fixed time period.

30. The system of claim 18, wherein the fixed time period is selected based on in situ acquisition of blood flow speed of the subject in the region of interest.

31. The system of claim 18, wherein the camera is configured to acquire at least two speckle images in synchronization with motion of a heart of the subject.

32. A computer program product for measuring blood flow distribution in principal vessels in a heart of a subject, the computer program product comprising:

a non-transitory computer-readable storage medium having computer-readable program code embodied in the medium, the computer-readable program code comprising;

computer readable program code configured to electronically evaluate temporal variation of the pixel intensities in the at least two acquired speckle images to generate a laser speckle contrast imaging (LSCI) image and determine spatial distribution of blood flow speed in the principal vessels and perfusion distribution in tissue in a region of interest in the heart from the LSCI image, wherein and a field of view including the region of interest is at least about 2 square centimeters and the at least two speckle images are sequentially acquired using a camera during a fixed time period when the region of interest of the subject is passively illuminated by a coherent light source having a wavelength of from about 600 nm to about 1100 nm; and

computer readable program code configured to sequentially acquire the at least two speckle images in synchronization with motion of the heart of the subject trigger the acquisition responsive to the motion of the heart of the subject.

33. The computer program product of claim 32, further comprising:

computer readable program code configured to calculate a velocity field for the region of interest in the heart;

computer readable program code configured to calculate blood flow rate in the region of interest in the heart based on the calculated velocity field; and

computer readable program code configured to compare the calculated blood flow speed in the region of interest to the blood flow speed determined using the acquired at least two speckle images of the region of interest in the heart to verify results obtained using the at least two speckle images.

34. The computer readable program code of claim 33, wherein the computer readable program code configured to calculate the velocity field further comprises computer readable program code configured to calculate the fields of velocity and rate based on the following equations with appropriate boundary and initial conditions: