Device and method for examining biological vessels

• US 6,621,917 B1
• Filed: 07/24/1998
• Issued: 09/16/2003
• Est. Priority Date: 11/26/1996
• Status: Expired due to Fees

• Current Assignee: Imedos-Intelligente Optische System Der Medizin-Und Messtechnik GmbH
• Original Assignee: Imedos-Intelligente Optische System Der Medizin-Und Messtechnik GmbH
• Inventors: Vilser, Walthard
• Primary Examiner(s): Mehta, Bhavesh M.
• Assistant Examiner(s): Choobin, Barry
• Application Number:
  US09/117,236
• Time in Patent Office: 1,880 Days
• Field of Search: 382/128, 382/100, 128/922, 356/39, 377/10, 707/104.1, 702/128, 606/5, 600/449, 600/443, 600/405, 600/439, 436/172, 351/212
• US Class Current: 382/128
• CPC Class Codes: A61B 3/1233 for measuring blood flow, e.g. at the retina
• CPC Class Codes: Y10S 128/922 including image analysis

Abstract

The present invention pertains to a device for examining biological vessels, especially retinal vessels, including an evaluation unit in the form of an image manipulator (BM) enabling at least partial digitalization or isolation of a measurement window, whereby at least one vessel segment is represented by an electronic picture or picture sequence, which is then transferred to said evaluation unit.

Claims

1. Device for the investigation of biological vessels, preferably of retinal vessels, in which at least one vessel section is present as an electronic image or as a series of electronic images, which is supplied from a photoelectric receiving device to an evaluation unit, whereby the evaluation unit contains an image manipulation unit (BM) for section by section digitizing or blanking of at least one measured window in the image created by the photoelectric receiving unit and for identification of the image and of the position of the measured window in the image;

a control unit (SS) to create the image identifier and the measured window coordinates which describe the position and geometry of the measured window in the image;

image-processing or signal-processing computing and storage units (BV) and output units (EP) for display of the image and/or display of measured values and/or of measured results,

whereby the arrangement contains means by which the component of the measuring window contains in the direction of the expanse of the vessel at least so many pixel positions that are detected that the inclined position of the vessel in relation to the measuring direction can be determined and the vessel diameter can be resolved in a manner selected from the group consisting of in terms of location by at least two vessel diameter values of directly neighboring vessel segments of the same vessel, and in terms of time by at least two vessel diameter values per the same vessel segment between different images.

2. Device according to claim 1, characterized in that the geometry and/or the position of the measured window in the image and its orientation in the image are controllable.

3. Device according to claim 1, characterized in that at least one measured window is of a strip design.

4. Device according to claim 3, characterized in that means are provided for switching between horizontal and vertical position.

5. Device according to claim 1, characterized in that the components of the measured surface transverse to the vessel run amount to 10-times that of the expected vessel diameter and that at least 6 pixels of a line or column are located simultaneously on the component of the measured window located transverse to the vessel run.

6. Device according to claim 1, characterized in that at least one measuring window is designed as a ring strip or as a ring polygonal section using rectangular strips preferably mutually overlapping at the corner.

7. Device according to claim 5, characterized in that for application to the background of the eye, the inner diameter of the ring or polygon section is at least as large as the diameter of the papilla.

8. Device according to claim 1, characterized in that means are provided so that at least a number of pixel layers can be adjusted as corresponds to the component of the measured window in the direction of the vessel run, so that the maximum and minimum changes in vessel diameter of the quasi-periodic, local changes in vessel diameter will be ascertained.

9. Device according to claim 1, characterized in that means are provided for manual or automatic definition of a scan region within which the measured window changes its position stochastically or systematically from one image to the next, and that the scan region is preferably at least 1.5 mm in size.

10. Device according to claim 1, characterized in that means are provided for changing the radius of the circular or polygon-shaped measured surface within a manually or automatically defined scan region, from one image to the next, and that the scan region is preferably at least 1.5 mm in size.

11. Device according to claim 1, characterized in that the photoelectric receiving device is an imaging system with at least one image receiver, and one illuminating beam path is provided and that in the plane of the illuminated beam path congruent to the object plane there is a partly transparent aperture for definition of a measured region, said aperture consists of a fully transparent measured field region and a partly transparent perimeter region.

12. Device according to claim 1, characterized in that the intensity of an illuminating light and/or the position of the partly transparent aperture can be controlled in the plane congruent to the object field by means of measured field coordinates.

13. Device according to claim 1, characterized in that the photoelectric receiving device is an imaging system with at least one receiver and has at least one illuminated beam path for perimeter lighting, and that at least one additional illuminated beam path is located in the lighted, main beam path which creates an additional, lighted measured field in the object plane, which is superimposed on a primary light, or separates the object field, from a lighting point of view, geometrically into the measured field and the perimeter field formed by the main beam path.

14. Device according to claim 13, characterized in that servoelements are provided that use measured field coordinates independently of the main lighting or perimeter lighting, to control the position and/or geometry and/or intensity and/or spectral properties and that the measured field coordinates are created by the control unit and transmitted to the servoelements.

15. Device according to claim 1, characterized in that means are provided with which the measured window and the measured surface can be set up and moved confocal.

16. Device according to claim 1, characterized in that means are provided in the image manipulation unit so that in addition to the measured window, at least one help window is created in the image with a fixed position to the image, which detects movements and/or positions of object edges in the help window and saves them as correction coordinates in a primary matrix and/or are used on an image for immediate correction of movements of the vessel middle positions in the image field during one image sequence.

17. Device according to claim 16, characterized in that the help window is identical to the measured window in the first image at the beginning of measurement.

18. Device according to claim 16, characterized in that the help window is designed as a strip-like window and at the beginning of measurement stands perpendicular and central to the measured window.

19. Device according to claim 1, characterized in that means are provided for spectral tuning of the lighting and/or imaging light, said means having a bandpass character with steep edges and properties such that they have the smallest possible tolerance for medium wavelength and bandwidth and reside in a series

20. Device according to claim 1, characterized in that for application on the eye, an inner and/or outer fixation device with fixation servoelements is provided, which unambiguously describes—

in defined fixation coordinates—

the angle between the optical axis of the eye and of the imaging system, performs the fixation setting and that means are provided to control and/or determine these fixation coordinates and also to transfer the fixation coordinates between control unit and fixation devices.

21. Device according to claim 1, characterized in that the fixation coordinates of the inner and of the outer fixation device are identical for the mutually overlapping fixation regions and that means are provided to control and/or determine these fixation coordinates and also to transmit the fixation coordinates between control unit and fixation devices.

22. Device according to claim 20, characterized in that refraction servoelements are provided with which the fixation marks can be focused for the patient one time before beginning the sequence of measured values and that through suitable refraction measurements, the adjusted fixation refraction value for focussing is measured and transmitted to the control unit.

23. Device according to claim 20, characterized in that an aperture is positioned in the illuminating beam path or behind the outer fixation mark so that it covers at least the foveola of the eye to be examined, or in the case of outer fixation, it covers the neighboring eye.

24. Device according to claim 1, characterized in that means are provided that stochastically change the brightness or shape of the fixation marks.

25. Device according to claim 1, characterized in that means are provided with which in the case of rough or indefinitely determined, relative shifts in position, an acoustical signal and/or a temporarily differently modulated brightness modulation or shape control of the fixation mark will occur.

26. Device according to claim 1, characterized in that means are provided with which at the beginning of the measurement, the entire image with measured window is saved as a control for the measured site.

27. Device according claim 1, characterized in that that means are provided which

recognize vessel edges in the digitized measured windows,

interpolate the photometric edge concentrations for all discernible vessel edges in the measured windows,

perform a vessel edge allocation by unambiguously assigning the determined values to individual vessel sections,

calculate the slant position of the vessels to the measured window from the local shift in middle or edge position of mutually cohesive vessel sections of the same image,

determine the vessel diameter from the slant-position-corrected distance of mutually cohesive photometric edge concentrations,

determine the vessel middle position in the image for each vessel diameter, and

save the determined vessel diameter and vessel middle positions in a primary data set for each recognized vessel, image by image.

28. Device according to claim 25, characterized in that means are provided for vessel allocation which take the current, recognized vessel and assign it unambiguously to the recognized vessels of the preceding images or define a new vessel and expand the primary data set by a new vessel.

29. Device according to claim 1 characterized in that means are provided for calculation and image-by-image storage of the average brightness in the present measured windows or measured window regions as the vessel signals in the primary data set describing the vessel diameter.

30. Device according to claim 28, characterized in that means are provided which determine the average brightness in the center as the vessel brightness, in the edge region as edge brightness, and in the vessel perimeter as perimeter brightness and save the data appropriate to each vessel in the primary data set.

31. Device according to claim 1, characterized in that additional measuring means (MS) are provided whose measured signals are allocated to and saved in the primary data set or control data set correctly for each image or image sequence.

32. Device according to claim 30, characterized in that the measuring means perform a quasi-continuous acquisition of blood pressure signals and/or intraocular pressure signals and/or EKG-signals and/or pulse signals.

33. Device according to claim 30, characterized in that the measuring means can be controlled by the control unit.

34. Device according to claim 1, characterized in that manipulation systems (MP) are provided which cause a defined change in biological parameters on the microcirculation and/or the metabolism and that the associated, provocation signals are saved in the primary data set allocated appropriately to each image.

35. Device according to claim 33, characterized in that the biological parameters are intraocular pressure and/or respiratory gas composition and/or physical stress and/or temperature and/or light stimulus.

36. Device according to claim 34, characterized in that the manipulations systems can be controlled by the control unit.

37. Device according to claim 1, characterized in that,

an on-line memory unit ES is provided for image sequences

the image manipulator supplies each image with an image identifier and measured sequence code

the image identifier and measured sequence code are created by the control signal unit and passed to the image manipulator and that the image identifier of the particular, evaluated image is saved in each primary data set and the measured sequence code is saved in the associated control data set.

38. Device according to claim 1, characterized in that units are provided for spectral analysis of the vessel signals and measured signals and for display and storage of the results of the spectral analysis.

39. Device according to claim 1, characterized in that, means are provided for optional time and space filtering of the vessel signals and that filtered vessel signals are sent to the unit for spectral analysis.

40. Method for the examination of biologic vessels, preferably of retinal vessels, in which at least one vessel section is present as an electronic image or as a sequence of electronic images which is sent from a photoelectric receiver to an evaluation unit, characterized in that vessel signals are created that described the vessel diameter of at least one vessel section by use of temporal and/or spatial resolution;

in a manner selected from the group consisting of by combining at least two vessel diameters of directly neighboring vessel segments and by combining at least two vessel diameters of the same vessel segment of images different in terms of time, to form one vessel signal.

41. Method according to claim 40, characterized in that in the acquisition of an image with a photoelectric receiving device, by means of the automatic or manual setting of at least one measured window, and by setting of a measured range and by means of multiple movement of the measured window within the measured range, measured data are created which represent at least one vessel diameter with spatial and temporal resolution.

42. Method according to claim 40, characterized in that the time-variable measured data of the measured window are recorded, saved and processed.

43. Method according to claim 40, characterized in that,

in accordance with a task-specific structure plan, images of the image sequence are evaluated or created in the specified number and at the specified time interval,

this time interval is used as the time basis of the vessel signal and

vessel signal values— together with the vessel middle position and/or measured window coordinates and/or measured field coordinates—

are allocated to each other in time and space for each evaluated image and saved in a primary data set.

44. Method according to claim 40, characterized in that the primary data sets of a measurement procedure are combined into a primary data matrix.

45. Method according to claim 40, characterized in that fixation and help window coordinates and/or scan regions and/or refraction value of the device for focusing the fixation mark are determined or formed which are not changed during a measuring process or during an image sequence and are allocated together with an identifier of the measuring process in a control data set for the primary data matrix of an image sequence.

46. Method according to claim 40, characterized in that in the help window and/or in the main window, the local shift of at least one characteristic image pattern in each evaluated image is determined in proper coordinates for the first image of a measurement process or for each preceding image and is saved with chronological accuracy as a help window correction value in the primary data set.

47. Method according to claim 46, characterized in that the characteristic image pattern is the actual vessel to be analyzed and the position of the vessel pattern is the position of the middle of the vessel.

48. Method according to claim 40, characterized in that the corrected vessel middle positions of the particular vessel diameter value are calculated from the fixation and/or measured window coordinates and/or the help window correction values with respect to a defined reference point in the image plane, and are saved with chronological accuracy in the primary data matrix.

49. Method according to claim 40, characterized in that the location-dependent vessel signals are frequency-analyzed before and/or after filtering as a function of the location and/or of the time;

the frequency spectrum and phase position are graphically displayed and/or subsequent local and/or chronological frequency parameters are determined and saved in a complex identifier matrix.

50. Method according to claim 49, characterized in that as identifiers, one or more of the quantities of vasomotion frequency, bandwidth, power and phase-position, pulsation frequency, bandwidth, power and phase position, and also frequency, phase position, bandwidth and power of additional detectable frequencies are used.

51. Method according to claim 40, characterized in that additional measured signals that describe parameters affecting the vessel diameter, are assigned to at least one value in the control data set of the image sequence or are assigned chronologically to the vessel signals in the primary data set.

52. Method according to claim 51, characterized in that blood pressure parameters and/or the intraocular pressure and/or pulse and/or heart phase are used as parameter factors.

53. Method according to claim 40, characterized in that additional manipulation signals that describe the artificially created parameters affecting the vessel diameter, are resolved in time (at least) and allocated to the vessel signals in the primary data set.

54. Method according to claim 40, characterized in that from the vessel signals, additional vessel signals are formed in which the square of the values and/or the 4th power of the values is formed and saved in the primary data sets.

55. Method according to claim 40, characterized in that characteristic quantities are formed from the vessel, measured and/or manipulation signals.

56. Method according to claim 40, characterized in that vessel signals and/or measured signals and/or manipulation signals and/or parameters are superimposed on the vessel image, or are allocated to or displayed as time-profiles and/or as local two- or three-dimensional profiles as functional diagnostic images and/or are presented numerically or graphically as complex, whole values independent of time and location.

57. Method according to claim 40, characterized in that after and/or before temporal and/or local filtering of the vessel signals, from the corrected vessel middle positions of the vessel signals, local regions and time regions are formed that include at least one value and that from the vessel signals within the local regions and time regions, location-dependent time parameters are determined and are saved and displayed in a time parameter matrix for the particular, defined time and location regions, and/or are output superimposed on the original image as a function of the corrected vessel middle position as a functional-diagnostic image for the defined time region and location region.

58. Method according to claim 57, characterized in that the location-dependent time parameters are maximum and minimum values with respect to time and/or with respect to the temporal average values from the vessel signals, their temporal scattering and confidence intervals and/or the roots of the temporal average value from the squares of the vessel diameter, the associated scattering and confidence intervals and/or the ¼

power of the temporal average value across the 4th power of the vessel diameter and their scatterings and confidence intervals.

59. Method according to claim 57, characterized in that heart pulse regions are defined and that for each local region—

by means of EKG-triggered signal average of the vessel signal or diameter—

the average value, scattering and confidence interval within the heart pulse regions are formed and saved.

60. Method according to claim 59, characterized in that pulse parameters such as the pulse phase position, the maximum pulse value and the minimum pulse value are determined from the pulse profile and saved.

61. Method according to claim 57, characterized in that the signal filters processing the vessel signals are bandpass filters with outlet connected, floating average value formation that select or smooth the heart pulsation and/or heart vasomotion and/or blood pressure waves of 1st and/or 2nd order and/or the respiratory frequency, and/or smooth foreign signals and/or interferences.

62. Method according to claim 40, characterized in that before and/or after a default local and/or temporal filtering of the vessel signals, temporal regions and vessel regions are formed that include at least one value and that from the local vessel runs within the time regions and vessel regions, time-dependent local parameters are determined and are saved in a local parameter matrix for the defined location and time region and are output graphically as a function of time for the particular vessel region.

63. Method according to claim 62, characterized in that the time-dependent local parameters are the maximum and minimum values and/or the local average value of the vessel signal, whose scattering and confidence intervals are formed, and in the local parameter matrix as a function of the time and/or that the roots of the local average value from the squares of the vessel diameter, the associated scattering and confidence intervals and/or the ¼

power of the local average value across the 4th power of the vessel diameter and its scattering and confidence intervals.

64. Method according to claim 62, characterized in that heart pulse ranges are specified and that for each time region, the average value, scattering and confidence interval within the heart pulse regions are formed as average values with respect to location by means of EKG-triggered signal averaging of the vessel signal or diameter and are saved and displayed.

65. Method according to claim 64, characterized in that pulse characteristic parameters are determined from the pulse profile and saved and that the pulse parameters are the local average pulse phase position, the local average pulse maximum value and the local average pulse minimum value.

66. Method according to claim 40, characterized in that complex parameters are formed from the local parameter matrix and/or time parameter matrix or primary data matrix and are saved in a time-independent and location-independent complex parameter matrix correctly with respect to vessel, time region and local region and output.

67. Method according to claim 66, characterized in that maximum and minimum value, temporal and local average and its scattering are formed from the local and/or time parameters and/or vessel signals, e.g., from the vessel diameter and/or that the root of the temporal and local average and its scattering is formed from the squares of the particular vessel signals and/or that the ¼

power of the temporal and local average and its scattering, is formed from the 4th power of the values of the vessel signals, e.g., the vessel diameter.

68. Method according to claim 40, characterized in that quotients and/or differences and/or percentage differences are formed as derived parameters from the location, time and complex parameters among and with each other, which are each saved in the location parameter matrices or time or complex parameter matrices and are displayed or output accordingly as location, temporal or complex parameters.

69. Method according to claim 68, characterized in that as derived parameters, the pulse peak values and vasomotion peak values are brought into a relation with each other and/or that the frequency powers and/or the frequencies or phase position of pulse and vasomotion are related as new parameters and/or the peak values of the vessel diameter are brought into a relationship relative to the local or temporal or complex average value.

70. Method according to claim 40, characterized in that dynamic parameters are determined by signal analysis from the time profiles of the provoked or pathologically or therapeutically induced signal changes and are saved in the complex parameter matrix or in the time parameter matrix as dynamic parameters correctly with respect to vessel and/or location and are displayed.

71. Method according to claim 70, characterized in that the dead time, the decay and rise time constants of the direct response and of the reactive phase of the vessel sections to oxygen inhalation and/or to isometric stress and/or to change in the intraocular pressure and/or to light stimulus are determined by local resolution or as a response of a vessel region.

72. Method according to claim 40, characterized in that different vessels and/or vessel regions of a vessel are analyzed simultaneously, or simultaneously or sequentially within the same image sequence and the intervals of the corrected vessel middle positions are converted into comparable vessel length units and are displayed graphically in two or three dimensions for a comparison of their vessel signals or parameters.

73. Method according to claim 40, characterized in that parameters are formed that pertain to local and/or temporal and/or complex changes in a vessel and/or vessel section with respect to a reference vessel or a vessel section.

74. Method according to claim 40, characterized in that simultaneous measurements of at least two associated vessel sections or vessel regions are carried out and that the phase difference of mutually associated vessel sections of a vessel region and/or different vessel regions is determined and/or in addition, the flow paths between the vessel sections are determined and from phase difference and flow paths, the pulse wave rate is determined and output.

75. Method according to claim 40, characterized in that the temporal and local relationships between the corrected and/or uncorrected vessel signals and the provocation signals and/or supplemental measured signals and/or parameters are displayed graphically in two and/or three dimensions.

76. Method according to claim 40, characterized in that the parameters are determined anew for each new, evaluated image and output in one of the graphic or text displays.

77. Method according to claim 40, characterized in that a control parameter calculates the positioning uncertainty with each image iteratively as the scattering of help window correction values in both directions and/or continuously displays the values and the final value of the measurement sequence is saved in the control parameter set with the measured value sequence.

78. Method according to claim 76, characterized in that for a particular value due to the parameter of positioning uncertainty, due to the sequence control an acoustical signal and/or a prominent visual signal is introduced to the brightness or shape of the fixation mark by means of the sequence control.

79. Method according to claim 77, characterized in that the acoustical or visual signal becomes greater with increasing positioning uncertainty.

80. Method according to claim 40, characterized in that the image quality parameters in the primary data set are saved in correct chronology for each evaluated image.

81. Method according to claim 79, characterized in that the image quality parameters are used for canceling of vessel signal values, provided the value is outside of a default value range.

82. Method according to claim 70, characterized in that the image quality parameters are used to provide each measured value with a weighting factor which has a particular value in the case of very good image quality, and has the value zero for very poor quality, and has a graduated value for values of image quality lying in between, and that these weighting factors are used in the determination of average values for greater weighting of more dependable measured values and for attenuating or elimination of more uncertain measured values.

83. Method according to claim 40, characterized in that the first image of a measurement sequence is saved in its entirety and allocated to the control set of the measured sequence, and the measured window and help window and/or the scan regions in the image are identified with associated naming of the measured sequence and are graphically displayed or output as a local measured image.

84. Method according to claim 40, characterized in that during repeat measurements, the measured and/or help window coordinates and shape and/or fixation coordinates and/or measured field coordinates and/or scan regions are automatically set to their defaults by the sequence controller or are displayed for manual setting, and that the local measured image of the preceding measurement process is presented.

85. Method according to claim 40, characterized in that the measured signals or parameters are presented graphically in their temporal or local profile or on-line with their determination.

86. Method according to claim 84, characterized in that the average value and a confidence interval of the average value are determined iteratively and displayed as current value with each evaluated image, or are displayed graphically with the measured signal.

87. Method according to claim 40, characterized in that the measured window and/or measured field within the specified scan region is moved between various images or within one image stochastically or by pixels or sections in the direction of vessel run.

88. Method according to claim 40, characterized in that various clinical standard questions are assigned to various progress controls for the measurement process, that the preparation of the image sequence or evaluation of an existing image sequence takes place for a measured process in the quantity of images and/or in the temporal image spacing and/or is controlled automatically with a specified control data set, that this data is saved as control parameter in a control data set and that the measurement process is terminated when the confidence interval falls below a default value.

89. Method according to claim 87, characterized in that the reproducibility desired by the examiner is requested in dialog mode and from the default control values, the needed number of measured values and/or examining time is computed.

90. Method according to claim 87, characterized in that an image sequence of at least 10 images/s over at least 10 s or at least 1 image/s over at least 120 s or at least 0.2 images/s over at least 600 s is recorded and/or evaluated.

91. Method according to claim 87, characterized in that an image sequence of at least 10 images is recorded and/or evaluated stochastically distributed over at least 5 minutes.

92. Method according to claim 40, characterized in that the sequence controller controls the lighting of the measured field and switches to full intensity only during the measurement and otherwise uses reduced values.

93. Method according to claim 40, characterized in that the lighting intensity in the measured field is regulated by the sequence control during the measurements and as control quantities, default values for the image quality parameters are used and the minimum light intensity needed for the specified image quality parameters is always used.