System and method of measuring changes in arterial volume of a limb segment

• US 8,057,400 B2
• Filed: 06/12/2009
• Issued: 11/15/2011
• Est. Priority Date: 05/12/2009
• Status: Active Grant

• Current Assignee: Angiologix, Inc. (Everist Genomics, Inc.)
• Original Assignee: Angiologix, Inc. (Everist Genomics, Inc.)
• Inventors: Konstantinov, Nikolay V., Parfenova, Maria A., Parfenov, Alexander S.
• Primary Examiner(s): Mallari; Patricia
• Assistant Examiner(s): JANG, CHRISTIAN YONGKYUN
• Application Number:
  US12/483,930
• Publication Number:
  US 20100292592A1
• Time in Patent Office: 886 Days
• Field of Search: 600/507, 600500-503, 600/504
• US Class Current: 600/507
• CPC Class Codes: A61B 5/02116 of pulse wave amplitude A61B5/02225 takes precedence
• CPC Class Codes: A61B 5/02125 of pulse wave propagation time
• CPC Class Codes: A61B 5/02141 Details of apparatus construction, e.g. pump units or housings therefor, cuff pressurising systems, arrangements of fluid conduits or circuits A61B5/02233, A61B5/0235 take precedence
• CPC Class Codes: A61B 5/022 by applying pressure to close blood vessels, e.g. against the skin; Ophthalmodynamometers
• CPC Class Codes: A61B 5/02225 using the oscillometric method
• CPC Class Codes: A61B 5/026 Measuring blood flow A61B3/1233, A61B3/1241 take precedence
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/4884 inducing physiological or psychological stress, e.g. applications for stress testing
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: A61B 5/7239 using differentiation including higher order derivatives

Abstract

A medical diagnostic device performs diagnostics for assessing the ability of the arteries to respond to an increase in blood flow. The medical diagnostic device determines relative changes in arterial volume of the limb segment during a time period after a stimulus relative to the arterial volume of the limb segment during a baseline period using the amplitudes or other portions of the component pulse waves (such as early systolic components) of volume pulse waves during the baseline period and after the stimulus.

Claims

1. A method for assessing change in arterial volume of a limb segment of a mammal, said method comprising:

determining amplitudes of component pulse waves of detected volume pulse waves of a limb segment detected during a baseline period to determine a baseline arterial volume of the limb segment;

applying a stimulus to the mammal to induce a period of change in the arterial volume of the limb segment;

determining amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after the stimulus has been applied to the mammal to induce a period of change in the arterial volume of the limb segment; and

determining relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb segment during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves during the baseline and after the stimulus;

wherein determining relative change in arterial volume of the limb comprises;

calculating an average component pulse wave amplitude during the baseline period;

generating a curve fit of component pulse wave amplitudes during the after-stimulus period;

calculating a maximum of the fitted curve;

determining a time between beginning of the after-stimulus period and the time of the maximum of the fitted curve;

determining a relative amplitude change from the baseline to the maximum of the fitted curve; and

determining a relative change in arterial volume from the relative amplitude change from the baseline to the maximum of the fitted curve and the average component pulse wave amplitude during the baseline period.

2. The method of claim 1, wherein the component pulse wave is an early systolic component.

3. The method of claim 2 wherein the determining relative change in arterial volume includes comparing maximum amplitudes of the early systolic components of the volume pulse waves during the baseline period and maximum amplitudes of the early systolic components of the volume pulse waves after the stimulus.

4. The method of claim 2, wherein determining amplitude of early systolic component of a volume pulse wave comprises:

determining an occurrence of an inflection point in the volume pulse wave;

determining a time of the occurrence of the inflection point;

determining a pressure value on the detected volume pulse wave at said time;

determining a pressure value at the beginning of the volume pulse wave; and

assessing the amplitude of the early systolic component of the volume pulse wave as the difference between said pressures values.

5. The method of claim 1, further comprising:

monitoring the limb segment to record the detected volume pulse waves of the limb segment during the baseline period;

monitoring the limb segment to record the detected volume pulse waves of the limb segment during a period of an after-stimulus period.

6. The method of claim 5 wherein the component pulse wave is an early systolic component.

7. The method of claim 1, wherein the stimulus comprises a mechanical stimulation, a thermal stimulation, a chemical stimulation, an electrical stimulation, a neurological stimulation, a mental stimulation or a physical exercise stimulation, or any combination thereof, to induce a change in arterial volume of the limb segment.

8. The method of claim 1, wherein applying the stimulus comprises inflating a cuff that is disposed on the limb segment to a pressure above systolic for a period of time sufficient to induce change in arterial volume of the limb segment after releasing the inflation pressure of the cuff.

9. The method of claim 8, further comprising:

monitoring blood oxygen in the limb distal to the cuff to standardize a degree of limb ischemia among a plurality of test subjects; and

quantifying an amount of stimulus in a particular patient in response to the standardized degree of limb ischemia among the plurality of test subjects.

10. The method of claim 1 wherein calculating an average pulse wave amplitude during the baseline comprises:

determining an average pulse wave amplitude for each inflation/deflation cycle of a plurality of inflation/deflation cycles over the baseline period; and

calculating an average pulse wave amplitude during the baseline from the average pulse wave amplitudes of the plurality of inflation/deflation cycles.

11. The method of claim 1 wherein generating a curve fit of pulse wave amplitudes comprises generating a fourth-order polynomial function to fit the after-stimulus pulse wave amplitudes.

12. The method of claim 1, wherein determining relative change in arterial volume of the limb further comprises integrating an area under the fitted curve from a time period of the end of the stimulus to a time when the measured amplitude returns to a baseline amplitude.

13. A method for assessing change in arterial volume of a limb segment of a mammal, said method comprising:

monitoring a limb segment to record detected volume pulse waves of the limb segment during a baseline period;

determining amplitudes of component pulse waves of the detected volume pulse waves of the limb segment detected during the baseline period to determine a baseline arterial volume of the limb segment;

applying a stimulus to the mammal to induce a period of change in the arterial volume of the limb segment;

monitoring the limb segment to record detected volume pulse waves of the limb segment during an after-stimulus period after the stimulus has been applied;

determining amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during the after-stimulus period; and

determining relative change in arterial volume of the limb segment during the after-stimulus period relative to the arterial volume of the limb segment during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves during the baseline and after-stimulus periods;

wherein monitoring the limb segment during the baseline and after-stimulus periods each comprise;

applying, in a series, an external pressure to the limb segment at a mean arterial pressure of the limb; and

detecting volume pulse waves of the limb segment.

14. A method for assessing change in arterial volume of a limb segment of a mammal, said method comprising:

monitoring a limb segment to record detected volume pulse waves of the limb segment during a baseline period;

determining amplitudes of component pulse waves of the detected volume pulse waves of the limb segment detected during the baseline period to determine a baseline arterial volume of the limb segment;

applying a stimulus to the mammal to induce a period of change in the arterial volume of the limb segment;

monitoring the limb segment to record detected volume pulse waves of the limb segment during an after-stimulus period after the stimulus has been applied;

determining amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during the after-stimulus period; and

determining relative change in arterial volume of the limb segment during the after-stimulus period relative to the arterial volume of the limb segment during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves during the baseline and after-stimulus periods;

wherein monitoring the limb segment during the baseline and after-stimulus periods each comprise;

applying an external pressure to the limb segment at a pressure level which allows blood flow through the artery to produce said volume pulse waves in response to the applied external pressure.

15. The method of claim 14, wherein applying the external pressure comprises

varying gradually the external pressure between near-systolic and near-diastolic, and

detecting the volume pulse waves while the external pressure is between systolic and diastolic.

16. The method of claim 14, wherein applying the external pressure comprises:

initially applying the external pressure at a pressure near systolic, and

gradually reducing the external pressure to a pressure near diastolic.

17. The method of claim 14, wherein applying the external pressure comprises:

initially applying the external pressure at a pressure near diastolic, and

gradually increasing to a pressure near systolic.

18. The method of claim 14, wherein applying the external pressure comprises cycling the external pressure between a high level and a low level, wherein determining the amplitudes of component pulse waves of the volume pulse waves includes said determining while the external pressure is at the high level.

19. The method of claim 18, wherein the high level is near mean arterial pressure and the low level is below venous pressure.

20. The method of claim 18, wherein the high level is below diastolic pressure and the low level is below venous pressure.

21. A method for assessing change in arterial volume of a limb segment of a mammal, said method comprising:

determining amplitudes of component pulse waves of detected volume pulse waves of a limb segment detected during a baseline period to determine a baseline arterial volume of the limb segment;

applying a stimulus to the mammal to induce a period of change in the arterial volume of the limb segment;

determining amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after a stimulus has been and

determining relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb segment during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves during the baseline and after the stimulus;

wherein the component pulse wave is an early systolic component; and

wherein determining amplitude of early systolic component of a volume pulse wave comprises;

computing a fourth derivative of the detected volume pulse wave;

determining a time at which the fourth derivative reaches a third zero crossing;

determining a pressure value on the detected volume pulse wave at said time;

determining a pressure value at the beginning of the volume pulse wave; and

assessing the amplitude of the early systolic component of the volume pulse wave as the difference between said pressures values.

22. The method of claim 21 wherein the determining the pressure value at the beginning of the volume pulse wave includes determining a minimum of the pulse wave corresponding to a diastole of a heart.

23. A diagnostic system for assessing change in arterial volume of a limb segment of a mammal comprising:

a sensor for detecting volume pulse waves of a limb segment during a baseline period and for detecting volume pulse waves of the limb segment during a period of an after-stimulus change in arterial volume;

a processor coupled to the sensor to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during the baseline period to determine a baseline arterial volume of the limb segment, to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after a stimulus has been applied to the mammal to induce a period of change in the arterial volume of the limb segment, and to determine relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves at baseline and after the stimulus;

wherein the processor calculates an average pulse wave amplitude during the baseline period, generates a curve fit of pulse wave amplitudes during the after-stimulus period, calculates a maximum of the fitted curve, determines a time between beginning of the after-stimulus period and the time of the maximum of the fitted curve, determines a relative amplitude change from the baseline to the maximum of the fitted curve, and determines a relative change in arterial volume from the relative amplitude change from the baseline to the maximum of the fitted curve and the average pulse wave amplitude during the baseline period to determine relative change in arterial volume of the limb.

24. The diagnostic system of claim 23, wherein the processor determines the relative change in arterial volume by comparing the amplitudes of the component pulse waves of volume pulse waves at baseline and after the stimulus.

25. The diagnostic system of claim 23, wherein the component pulse wave is an early systolic component.

26. The diagnostic system of claim 25, wherein the processor determines the relative change in arterial volume by comparing maximum amplitudes of the early systolic components of the volume pulse waves during the baseline period and maximum amplitudes of the early systolic components of the volume pulse waves after the stimulus.

27. The diagnostic system of claim 25, wherein the processor determines an occurrence of an inflection point in the volume pulse wave, determines a time of the occurrence of the inflection point, determines a pressure value on the detected volume pulse wave at said time, determines a pressure value at the beginning of the volume pulse wave, and assesses the amplitude of the early systolic component of the volume pulse wave as the difference between said pressures values to determine the amplitude of early systolic component of a volume pulse wave.

28. The diagnostic system of claim 23, further comprising a pressure cuff coupled to the sensor and the processor for applying a pressure to the limb segment to occlude an artery in the limb segment and for releasing said pressure to the limb segment to allow blood flow in the artery to induce the period of change in arterial volume of the limb segment in response to a control signal from the processor.

29. The diagnostic system of claim 23, further comprising a pressure cuff coupled to the sensor and the processor to apply a stimulus to the mammal to induce a period of change in arterial volume of the limb segment.

30. The diagnostic system of claim 23, further comprising a pressure cuff coupled to the sensor and the processor to apply a stimulus to the mammal by inflating to a pressure above systolic for application to the limb segment for a period of time sufficient to induce change in arterial volume of the limb segment after releasing the inflation pressure of the cuff.

31. The diagnostic system of claim 30, further comprising:

a blood oxygen sensor coupled to the processor to monitor the limb distal to the cuff to standardize a degree of limb ischemia among a plurality of test subjects; and

wherein the processor quantifies an amount of stimulus in a particular patient in response to the standardized degree of limb ischemia among the plurality of test subjects.

32. The diagnostic system of claim 23, wherein the processor determines an average pulse wave amplitude for each inflation/deflation cycle of a plurality of inflation/deflation cycles over the baseline period, and calculates an average pulse wave amplitude during the baseline from the average pulse wave amplitudes of the plurality of inflation/deflation cycles to calculate an average pulse wave amplitude during the baseline.

33. The diagnostic system of claim 23, wherein the processor generates a fourth-order polynomial function to fit the after-stimulus pulse wave amplitudes to generate a curve fit of pulse wave amplitudes.

34. The diagnostic system of claim 23, wherein the processor integrates an area under the fitted curve from a time period of the end of the stimulus to a time when the measured amplitude returns to a baseline amplitude to determine relative change in arterial volume of the limb.

35. A diagnostic system for assessing change in arterial volume of a limb segment of a mammal comprising:

a sensor for detecting volume pulse waves of a limb segment during a baseline period and for detecting volume pulse waves of the limb segment during a period of an after-stimulus change in arterial volume;

a processor coupled to the sensor to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during the baseline period to determine a baseline arterial volume of the limb segment, to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after a stimulus has been applied to the mammal to induce a period of change in the arterial volume of the limb segment, and to determine relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves at baseline and after the stimulus; and

a pressure cuff coupled to the sensor and the processor to apply a stimulus to the mammal by inflating to a pressure above systolic for application to the limb segment for a period of time sufficient to induce change in arterial volume of the limb segment after releasing the inflation pressure of the cuff;

wherein the processor controls the cuff to apply, in a series, an external pressure to the limb segment at a mean arterial pressure of the limb, and controls the sensor to detect volume pulse waves of the limb segment during the baseline and after the stimulus.

36. A diagnostic system for assessing change in arterial volume of a limb segment of a mammal comprising:

a sensor for detecting volume pulse waves of a limb segment during a baseline period and for detecting volume pulse waves of the limb segment during a period of an after-stimulus change in arterial volume;

a processor coupled to the sensor to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during the baseline period to determine a baseline arterial volume of the limb segment, to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after a stimulus has been applied to the mammal to induce a period of change in the arterial volume of the limb segment, and to determine relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves at baseline and after the stimulus; and

a pressure cuff coupled to the sensor and the processor to apply a stimulus to the mammal by inflating to a pressure above systolic for application to the limb segment for a period of time sufficient to induce change in arterial volume of the limb segment after releasing the inflation pressure of the cuff;

wherein the processor controls the cuff to apply an external pressure to the limb segment at a pressure level which allows blood flow through the artery to produce said volume pulse waves in response to the applied external pressure during the baseline and after the stimulus.

37. The diagnostic system of claim 36, wherein the processor controls the cuff to apply the external pressure to the limb segment as a gradually varying pressure between near-systolic and near-diastolic, and

wherein the processor controls the sensor to detect the volume pulse waves while the external pressure is between systolic and diastolic.

38. The diagnostic system of claim 36, wherein the processor controls the cuff to apply the external pressure to the limb segment at a pressure near systolic, and gradually reducing the pressure to near diastolic.

39. The diagnostic system of claim 36, wherein the processor controls the cuff to apply the external pressure to the limb segment at a pressure near diastolic, and gradually increasing to the pressure to near systolic.

40. The diagnostic system of claim 36, wherein the processor controls the cuff to cycle the external pressure applied to the limb segment between a high level and a low level,

wherein the processor determines the amplitudes of component pulse waves of the volume pulse waves detected while the external pressure is at the high level.

41. The diagnostic system of claim 36, wherein the high level is near mean arterial pressure and the low level is below venous pressure.

42. The diagnostic system of claim 36, wherein the high level is below diastolic pressure and the low level is below venous pressure.

43. A diagnostic system for assessing change in arterial volume of a limb segment of a mammal comprising:

a sensor for detecting volume pulse waves of a limb segment during a baseline period and for detecting volume pulse waves of the limb segment during a period of an after-stimulus change in arterial volume; and

a processor coupled to the sensor to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during the baseline period to determine a baseline arterial volume of the limb segment, to determine amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after a stimulus has been applied to the mammal to induce a period of change in the arterial volume of the limb segment, and to determine relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves at baseline and after the stimulus;

wherein the component pulse wave is an early systolic component; and

wherein the processor computes a fourth derivative of the detected volume pulse wave, determines a time at which the fourth derivative reaches a third zero crossing, determines a pressure value on the detected volume pulse wave at said time, determines a pressure value at the beginning of the volume pulse wave, and assesses the amplitude of the early systolic component of the volume pulse wave as the difference between said pressures values to determine the amplitude of early systolic component of a volume pulse wave.

44. The diagnostic system of claim 43, wherein the processor determines a minimum of the pulse wave corresponding to a diastole of a heart of the mammal to determine the pressure value at the beginning of the volume pulse wave.

45. A non-transitory machine-readable medium encoded with instructions, that when executed by one or more processors, cause the processor to carry out a process for assessing change in arterial volume of a limb segment of a mammal, the process comprising:

determining amplitudes of component pulse waves of detected volume pulse waves of a limb segment detected during a baseline period to determine a baseline arterial volume of the limb segment;

determining amplitudes of component pulse waves of detected volume pulse waves of the limb segment detected during a time period after a stimulus has been applied to the mammal to induce a period of change in the arterial volume of the limb segment; and

determining relative change in arterial volume of the limb segment during the time period after the stimulus relative to the arterial volume of the limb during the baseline period from the amplitudes of the component pulse waves of the detected volume pulse waves at baseline and after the stimulus;

wherein determining relative change in arterial volume of the limb comprises;

calculating an average component pulse wave amplitude during the baseline period;

generating a curve fit of component pulse wave amplitudes during the after-stimulus period;

calculating a maximum of the fitted curve;

determining a time between beginning of the after-stimulus period and the time of the maximum of the fitted curve;

determining a relative amplitude change from the baseline to the maximum of the fitted curve; and

determining a relative change in arterial volume from the relative amplitude change from the baseline to the maximum of the fitted curve and the average component pulse wave amplitude during the baseline period.

46. The non-transitory machine-readable medium encoded with instructions of claim 45, wherein the component pulse wave is an early systolic component.

47. The non-transitory machine-readable medium encoded with instructions of claim 45, wherein the instructions for determining relative change in arterial volume includes instructions for comparing maximum amplitudes of the early systolic components of the volume pulse waves during the baseline period and maximum amplitudes of the early systolic components of the volume pulse waves after the stimulus.

48. The non-transitory machine-readable medium encoded with instructions of claim 45, further comprising instructions for monitoring the limb segment to record the detected volume pulse waves of the limb segment during the baseline period, and instructions for monitoring the limb segment to record the detected volume pulse waves of the limb segment during the after-stimulus period.

49. The non-transitory machine-readable medium encoded with instructions of claim 48, wherein the component pulse wave is an early systolic component.