METHOD AND APPARATUS FOR DETERMINING VASCULAR HEALTH CONDITIONS

• US 20070225614A1
• Filed: 11/27/2006
• Published: 09/27/2007
• Est. Priority Date: 05/26/2004
• Status: Abandoned Application

• Current Assignee: Endothelix, Inc.
• Original Assignee: Endothelix, Inc.
• Inventors: O'Brien, Timothy, Johnson, Mark, Jamieson, Craig, Naghavi, Morteza
• Application Number:
  US11/563,676
• Publication Number:
  US 20070225614A1
• Time in Patent Office: Days
• US Class Current: 600/549
• CPC Class Codes: A61B 2560/0242 adapted to measure environmental factors, e.g. temperature, pollution
• CPC Class Codes: A61B 5/0008 Temperature signals
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/02416 using photoplethysmograph signals, e.g. generated by infrared radiation A61B5/14552 takes precedence
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/4035 Evaluating the autonomic nervous system
• CPC Class Codes: A61B 8/08 Detecting organic movements or changes, e.g. tumours, cysts, swellings A61B8/02 - A61B8/06 take precedence
• CPC Class Codes: A61B 8/488 involving Doppler signals

Abstract

The present invention provides methods and apparatus for assessing a patient'"'"'s vascular health including endothelial function by monitoring changes in hemodynamic parameters responsive to the introduction of a vasostimulant. The invention provides a thermal energy measurement apparatus including a thermal energy sensor adapted to measure temperature of a body part while not substantially changing the temperature of the body part, and a display or recorder coupled to the thermal energy sensor, wherein the thermal energy sensor measures the temperature of the body part before and subsequent to the provision of a vasostimulant, and the display or recorder reports the temperature of the body part prior to the provision of the stimulant and the temperature of the body part after provision of the stimulant. Also provides are methods and apparatus providing for a second thermal energy sensor on a corresponding contralateral site to the site subject to the vasostimulant and simultaneously monitoring and recording of temperature of the contralateral site as a measure of neurovascular status and microvascular reactivity.

Claims

1. A thermal energy measurement apparatus, comprising:

a thermal energy sensor adapted to measure temperature of a body part while not substantially changing the temperature of the body part, and

a display or recorder coupled to the thermal energy sensor, wherein the thermal energy sensor measures the temperature of the body part before and subsequent to the provision of a vasostimulant, and the display or recorder reports the temperature of the body part prior to the provision of the stimulant and the temperature of the body part after provision of the stimulant.

2. The apparatus of claim 1, where the vasostimulant is physical such as an occlusive means for providing a reactive hyperemia stimulant by interrupting the blood flow to the body part for a period of time followed by ceasing the interruption of blood flow.

3. The apparatus of claim 1, where the vasostimulant is chemical such as a local or systemic administration of the stimulant for inducing vascular dilation or constriction.

4. The apparatus of claim 1, wherein the vasostimulant is a vascular or neurovascular stimulant.

5. The apparatus of claim 1, further comprising a plotting engine that plots a temperature curve at least between the temperature of the body part prior to the provision of the vasostimulant and the temperature of the body part after provision of the vasostimulant.

6. The apparatus of claim 1,wherein the apparatus records one or more parameters selected from the group consisting of:

lowest temperature of the body part;

the highest temperature of the body part;

the difference between the highest temperature of the body part and the temperature of the body part prior to the provision of the vasostimulant;

the difference between the highest temperature of the body part and the lowest temperature of the body part;

the time required for the temperature of the body part to stabilize subsequent to the provision of the vasostimulant;

the slope of the temperature changes of the body part from the temperatures of the body part upon the provision of the vasostimulant up to the lowest temperature of the body part achieved;

the slope of the temperature changes of the body part from the lowest temperature of the body part achieved up to the highest temperature of the body part achieved;

the area bounded by the temperature curve, the lower temperature of the body part achieved, the time at which the lowest temperature of the body part was achieved, and the time at which the highest temperature of the body part was achieved.

7. The apparatus of claim 1, wherein the device further comprises a unit for measuring a hemodynamic parameter such as blood flow velocity using ultrasound Doppler.

8. The apparatus of claim 1, wherein the device further comprises a unit for measuring a vascular physiologic parameter such as pulse wave velocity.

9. The apparatus of claim 1, wherein the device further comprises a unit for measuring and recording hemodynamic parameters using near infrared light such as photoplethysmography.

10. The apparatus of claim 1, wherein the device further comprises a unit for measuring a hemodynamic parameter using laser Doppler flowmetry.

11. The apparatus of claim 1, wherein the device further comprises a unit for measuring blood pressure.

12. The apparatus of claim 1, wherein the device further comprises a unit for measuring vital signs such as body temperature, heart rate, and blood oxygen.

13. The apparatus of claim 1, wherein the thermal energy sensor comprises a plurality of thermal energy sensors.

14. The apparatus of claim 1, further comprising one or more further monitoring units selected from a group consisting of a unit for:

skin color, nail capilloroscopy, ultrasound brachial artery imaging, forearm plethysmography, fingertip plethysmography, oxygen saturation change, blood pressure or vital signs monitoring device, Doppler flow measurement, arterial pulse waveform analysis, near-infrared spectroscopy measurement, peripheral arterial tonometry, and aortic augmentation index.

15. The apparatus of claim 1, further comprising one or more units for measuring room temperature measurement, core temperature measurement, and combinations thereof.

16. The apparatus of claim 1, comprising a computer system that is coupled to the thermal energy sensor by a wireless connection.

17. The apparatus of claim 16, wherein the wireless connection comprises Bluetooth technology.

18. The apparatus of claim 16, wherein the computer system is chosen from the group consisting of a cellular phone, a PDA, a personal computing device, and combinations thereof.

19. The apparatus of claim 1, further comprising a unit for measuring tissue metabolic rate.

20. The apparatus of claim 1, further comprising a unit for measuring tissue heat capacity.

21. The apparatus of claim 16, wherein the computer system is coupled to an alerting device.

22. The apparatus of claim 11, wherein the blood pressure of the subject is measured using finger blood pressure and/or wrist blood pressure.

23. The apparatus of claim 1, further comprising a pulse oximeter.

24. The apparatus of claim 1, wherein the thermal energy sensor is adapted to be coupled to a surface of the body part by an attachment selected from a group consisting of a:

mesh sleeve, ring, non-insulating material, mesh, disposable adhesive, watch, bracelet, or an article of clothing such as a glove.

25. The apparatus of claim 1, wherein the thermal energy sensor comprises a probe operable to measure thermal energy of the surface of the body part without contacting the body part.

26. The apparatus of claim 1, wherein the thermal energy sensor is operable to measure thermal energy over a time period.

27. The apparatus of claim 1, further comprising a second thermal energy sensor adapted for measurement of temperature of a corresponding contralateral body part while not substantially changing the temperature of the body part.

28. The apparatus of claim 27, is used to evaluate neurovascular reactivity of the subject and thereby to evaluate vascular and neurovascular health.

29. The apparatus of claim 1, wherein the thermal energy sensor is selected from among a group consisting of:

a thermocouple, thermister, resistance temperature detector, heat flux detector, liquid crystal sensor, thermopile, and an infrared sensor.

30. The apparatus of claim 1, further comprising a Doppler flow measurement device and is capable of continuous monitoring of Doppler flow velocity at an arterial site.

31. The apparatus of claim 1, further comprising a recording and calculating computer for continuously evaluating temperatures measured by the sensor in response to the vasostimulant, wherein the computer calculates one or more vascular responsiveness determinants selected from TF, TR, NP, SF and SR of the temperature response to the vasostimulant.

59. A computer program encoded on a computer-readable medium having a computer program recorded thereon and arranged to be loaded into a program memory of a computer and to cause the computer to execute at least the following steps for determining one or more health conditions:

retrieving a plurality of temperature data from a database, the temperature data derived from operation of the apparatus of claim 1, and including a baseline temperature of a target body part prior to administration of the vasostimulant and a temperature at a set time after administration of the vasostimulant;

calculating a difference between the baseline temperature and the temperature at a set time after administration of the vasostimulant; and

displaying the calculated difference.

60. The computer program of claim 59, wherein the temperature data further comprises one or more values selected from the group consisting of:

a temperature drop from the baseline temperature having a first slope;

a lowest temperature achieved;

a temperature rise from the lowest temperature achieved having a second slope;

a peak temperature; and

a stabilization temperature.

32. A method for assessment of vascular reactivity in an individual comprising:

locating a thermal energy sensor on a target site on the individual, wherein the thermal energy sensor does not alter microcapillary flow, and establishing a stable baseline temperature with the thermal energy sensor at the site;

providing a vasostimulant to the individual;

determining a temperature response to the vasostimulant; and

establishing a vascular reactivity assessment for the individual based on the temperature response.

33. The method of claim 32, wherein the vasostimulant comprises occluding a blood supply to the target site for a predetermined period of time and ceasing occlusion thereafter.

34. The method of claim 32, wherein the target site is an extremity.

35. The method of claim 32, further comprising measuring blood pressure in the individual.

36. The method of claim 32, further comprising monitoring a temperature response on a site remote from the target site.

37. The method of claim 32, comprising locating a second thermal energy sensor on a corresponding contralateral site to the site subject to the vasostimulant and simultaneously monitoring and recording of temperature of the contralateral site.

38. The method of claim 32, wherein the temperature is monitored successively from an establishment of the baseline until at least a peak temperature response.

39. The method of claim 38, wherein the successively monitored temperature is displayed as a plot of temperature versus time.

40. The method of claim 32, wherein one or more numerical values are obtained from the temperature response, the values selected from the group consisting of one or more of:

TF, TR, NP, SF, SR, and area under the curve.

41. The method of claim 32, wherein the health condition is selected from the group consisting of:

endothelial function, autonomic nervous system function, risk for atherosclerotic cardiovascular disorder, progression of heart failure, obesity, high sympathetic reactivity, high blood pressure, white coat hypertension, hypertension, smooth muscle cell dysfunction, status and progression of diabetes, fitness, sleep disorders such as sleep apnea, rheumatologic disease, Raynaud'"'"'s, connective tissue disorders, pulmonary hypertension, smoking, vascular stress, sleep disorders, metabolic syndrome, subclinical hypothyroidism, vascular dementia, Alzheimer'"'"'s, portal hypertension, cancer, renal function, cerebral vascular disease, stroke, memory loss, vision loss, heart attack, angina, erectile dysfunction, peripheral arterial disease, migraine headaches, Prinzmetal'"'"'s angina, pregnancy and preeclempsia, infections, HIV and AIDS, diabetic foot, anxiety and excessive stress, and high cholesterol as well as monitoring response to therapies for the aforementioned health conditions.

42. The method of claim 32, wherein the health condition is selected from the group consisting of post surgery and vascular interventions monitoring, monitoring wound healing and wound care management, and assessment of neurovasculopathy.

43. The method of claim 32, further comprising considering the vascular reactivity assessment in light of a status of the individual for one or more additional tests selected from the group consisting of:

coronary calcium score, Framingham risk score, cartoid intima-media thickness test, cardiac function test, magnetic resonance imaging test, intravascular ultrasound;

assessing a endothelial function, including by an endothelial driven microparticles test, a VCAM1 test, an ICAM1 test, a SELECTIN test, a VWF test, c-reactive protein test, an Lp-PLA2 level, a CD54 test, and ankle-brachial blood pressure index test.

44. The method of claim 32, further comprising measuring a hemodynamic parameter in the subject using optical spectroscopy.

45. The method of claim 32, further comprising measuring and recording a room temperature and/or a core temperature of the subject.

46. The method of claim 32, further comprising measuring and recording a tissue heat capacity and/or a tissue metabolic rate of the subject.

47. The method of claim 32, further comprising measuring and recording the blood pressure of the subject, including by Korotkoff sounds and/or oscillometric methods.

48. The method of claim 32, further comprising determining an oxygen saturation measurement at a fingertip.

49. The method of claim 32, further comprising measuring a blood flow velocity through an artery of the subject which supplies blood to the body part before, during, and after the provision of the vasostimulant.

50. The method of claim 32, further comprising measuring and recording the stiffness of an artery supplying blood to the body part by arterial pulse waveform analysis.

51. The method of claim 32, wherein the device acquires a measure of endothelium dependent vascular reactivity by the temperature response to the vasostimulant;

acquires a measure of endothelium independent vascular reactivity by input of additional non-endothelial related diagnosis techniques;

calculates a ratio of the measure of endothelium dependent vascular reactivity over the measure of endothelium independent vascular reactivity; and

thereby determines a health condition of the subject.

52. The method of claim 32, further comprising determining one or more health conditions by considering results of additional diagnostic techniques selected from the group consisting of:

intravascular optical coherent tomography, coronary fractional flow reserve, intravascular ultrasound radiofrequency backscatter analysis or Virtual Histology, urinary albumin, serum fibrinogen, IL6, CD40/CD40L, serum amyloid A, ankle brachial index, MRI, coronary calcium score, caratoid intermedia thickness, Framingham risk score, C-reactive protein tests, waist circumference, blood insulin level, PAI-1 test, t-PA test, glucose tolerance tests, fasting plasma glucose level, HDL cholesterol level, fasting plasma insulin test, homeostasis model assessment, BMI, body fat level, visceral fat test, subcutaneous fat test, white blood cell count, Neutrophil/lymphocyte ratio, platelet function test, and combinations thereof.

53. The method of claim 32, further comprising determining one or more health conditions by considering results of additional diagnostic techniques selected from the group consisting of:

plasma and urinary level of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine, exhaled nitric oxide, serum homosysteine, an endothelial driven microparticles test, a VCAM1 test, an ICAM1 test, a SELECTIN test, a VWF test, a TF test, a CD54 test, endothelial progenitor cells, myeolo-proxidase (MPO), increased neutrophil/lymphocyte ratio, endothelin- 1, thrombomodulin, tissue factor and tissue factor pathway inhibitor, markers of inflammation such as, for example, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage chemoattractant protein-1 (MCP-1) nitric oxide and its metabolites nitrates and nitrites, almost nitrosylated proteins, a selectin such as, for example, soluble endothelium, leukocyte, and platelet selecting, markers of oxidative stress including but not limited to free radical measurements of the blood or through the skin, TBAR, and/or extra cellular super oxide dismutase activity, vascular stiffness or compliance, and combinations thereof.

54. The method of claim 32, further comprising performing one or more additional diagnostic techniques in order to determine the health condition of the patient, the techniques selected from the group consisting of:

skin color, nail capilloroscopy, ultrasound brachial artery imaging, forearm plethysmography, fingertip plethysmography, oxygen saturation change, pressure change, near-infrared spectroscopy measurements, Doppler flow, peripheral arterial tonometry, and combinations thereof.

55. A treatment for improving vascular function, wherein the treatment is determined to be efficacious in improving vascular function based on an increase in normalized TR, SlopeR and/or NP digital thermal monitoring values as a consequence of the treatment.

56. The treatment of claim 55, wherein the treatment is a drug treatment.

57. The treatment of claim 55, wherein the treatment is a nutritional program.

58. A method for determining influence of a treatment on vascular function, comprising:

determining one or more normalized values selected from a TF, TR, SlopeR and/or NP value for a patient by digital thermal monitoring;

administering the treatment to the patient;

monitoring the patient for any change in one or more of the normalized values by periodic repeat determinations in the patient;

establishing that the treatment influences vascular function if a significant change in one or more of the normalized values result from administration of the agent.