Measurement of capillary related interstitial fluid using ultrasound methods and devices

• US 20040127790A1
• Filed: 10/09/2003
• Published: 07/01/2004
• Est. Priority Date: 08/19/1997
• Status: Abandoned Application

• Current Assignee: John D. Mendlein, Philipp Lang
• Original Assignee: John D. Mendlein, Philipp Lang
• Inventors: Mendlein, John D., Lang, Philipp
• Application Number:
  US10/682,808
• Publication Number:
  US 20040127790A1
• Time in Patent Office: Days
• US Class Current: 600/438
• CPC Class Codes: A61B 8/0858 involving measuring tissue layers, e.g. skin, interfaces
• CPC Class Codes: A61B 8/4236 characterised by adhesive patches
• CPC Class Codes: A61B 8/4422 related to hygiene or sterilisation
• CPC Class Codes: A61B 8/4472 Wireless probes

Abstract

The present invention provides for methods and devices for monitoring capillary related interstitial thickness. The invention also includes methods of measuring capillary related interstitial fluid, as well as cardiac, vascular, renal and hepatic function. Specific devices, particularly probes, are provided for such methods.

Claims

1. A method of detecting capillary related edema in a subject, comprising:

a) positioning an ultrasound probe on an epidermal surface of an appendage region of a subject in need of capillary related edema detection and said subject is suspected of comprised or challenged cardiac, arterial, venous, renal, hepatic function,

b) applying at least one ultrasound pulse to a subcutaneous layer of said appendage region,

c) recording a least one ultrasound signal with said ultrasound probe from said appendage region, and

d) detecting the presence or absence of a capillary related edema layer in said subcutaneous layer of said appendage region from said at least one ultrasound signal.

2. The method of claim 1, wherein said subject is a human.

3. The method of claim 2, wherein said appendage region is a tibia region.

4. The method of claim 3, wherein said detecting of said capillary related edema layer extends from an inner surface of skin to either a bone or fat surface in said tibia region.

5. The method of claim 4, wherein said recording does not determine the degree of skin echogenicity.

6. The method of claim 5, further comprising calculating a distance from said inner surface to said bone or fat surface of said tibia region.

7. The method of claim 6, wherein said distance is calculated by determining the shortest reflective distance.

8. The method of claim 6, wherein said human has diabetes, compromised renal function or compromised cardiac function.

9. The method of claim 8, further comprising:

a) administering a diuretic agent, a cardiac agent or a diabetic agent,

b) positioning an ultrasound probe on an appendage region of a subject in need of capillary related edema detection after said administration, and

c) recording ultrasound signals with said ultrasound probe from said appendage region;

d) wherein said ultrasound signals can be used to measure a capillary related edema layer in said appendage region after said administration.

10. The method of claim 5, wherein said ultrasound probe is an autonomous, hand-held ultrasound system capable of self measurement.

11. The method of claim 10, wherein said ultrasound system has a grip that readily permits said human to position said ultrasound probe on said tibia region of said human and said ultrasound system permits said human to monitor said capillary related edema layer.

12. The method of claim 8, further comprising measuring said capillary related edema layer between the inner surface of the skin and the anterior aspect of the tibia based on said at least one ultrasound signal.

13. The method of claim 12, wherein said measuring further comprises measuring skin thickness with said at least one ultrasound signal.

14. The method of claim 12, further comprising comparing said capillary related edema layer to a standard subcutaneous layer thickness for said tibia region, wherein said tibia region is about halfway between the ankle joint and the knee joint.

15. The method of claim 14, wherein said comparing comprises subtracting said standard subcutaneous layer thickness from said capillary related edema layer thickness or dividing said capillary related edema layer by said standard subcutaneous layer thickness to assess the amount of capillary related edema in the lower extremity.

16. The method of claim 1, wherein said capillary related edema is not in a non-muscle organ.

17. The method of claim 1, wherein further comprising:

a) positioning an ultrasound probe on an appendage region of said subject in need of capillary related edema detection 24 or more hours after detecting said capillary related edema layer, and

b) recording ultrasound signals with said ultrasound probe from said appendage region;

c) wherein said ultrasound signals can be used to measure a change of said capillary related edema layer in said appendage region after detecting said capillary related edema layer.

18. A dedicated ultrasound system for measuring capillary related edema, comprising an appendage ultrasound probe having a probe head and grip adapted for positioning said appendage probe on an appendage, and a computational unit.

19. The dedicated ultrasound system of claim 18, wherein said system is dedicated for self measurement and said grip is adapted for self measurement.

20. The dedicated ultrasound system of claim 19, wherein said appendage ultrasound probe has a self operator display.

21. The dedicated ultrasound system of claim 20, wherein said grip is no less than about 9 to 12 cm and no more than about 18 to 30 cm.

22. The dedicated ultrasound system of claim 19, wherein said grip projects from a surface of said appendage at about a 30 to 60 degree angle when said probe head is flush with said surface.

23. The dedicated ultrasound system of claim 19, wherein said system is an autonomous, hand-held ultrasound system.

24. The dedicated ultrasound system of claim 19, wherein said computational unit comprises a computer program to calculate capillary related edema layer thickness.

25. The dedicated ultrasound system of claim 19, wherein said computer program comprises a standard thickness for skin layer thickness.

26. A health care kit comprising:

a) a dedicated ultrasound system for measuring capillary related edema, comprising an appendage ultrasound probe having a probe head and grip adapted for positioning said appendage probe, and

b) a computational unit; and

c) a health care product in at least one dosage;

wherein said system can monitor for a therapeutic effect of said dosage.

27. The therapeutic kit of claim 26, wherein said health care product enhances water loss.

28. The therapeutic kit of claim 27, wherein said health care product is a drug selected from the group consisting of antiarrhythmics, anticholinergics, antihypertensives, alpha- and beta-adrenergic blockers, calcium channel blockers, cardiac glycosides, hydantoin derivatives, and nitrates.

29. The therapeutic kit of claim 26, wherein said health care product enhances cardiovascular function.

30. The therapeutic kit of claim 27, wherein said health care product is a drug selected from the group consisting of diuretics such as aldosteron antagonists, carbonic anhydrase inhibitors, loop diuretics and thiazides or thiazide-like agents

31. The therapeutic kit of claim 26, wherein said health care product enhances renal function.

32. The therapeutic kit of claim 27, wherein said health care product a drug selected from the group consisting of anticoagulants and vasoactive substances.

33. A method of measuring capillary related interstitial fluid, comprising:

a) transmitting at least one ultrasound pulse to a tissue in a subject in need of capillary related interstitial fluid assessment,

b) recording at least one ultrasound signal from said tissue, and

c) determining a capillary related interstitial layer thickness from a first reflective surface to an internal reflective surface, wherein said capillary related interstitial layer thickness is an assessment of capillary related interstitial fluid.

34. The method of claim 33, wherein said first reflective surface is a probe skin interface and said internal reflective surface is from a bone.

35. The method of claim 34, wherein said tissue is located in an appendage and said subject is a human.

36. The method of claim 35, wherein said steps (a), (b), and (c) are performed prior to a medical treatment and a first capillary related interstitial layer thickness is determined and further comprising repeating said steps (a), (b), and (c) after, or simultaneous to, said medical treatment and during a clinically relevant time period, and further comprising comparing a second capillary related interstitial layer thickness to said first interstitial layer thickness, wherein if said second capillary related interstitial layer thickness is larger than said first capillary related interstitial layer thickness then said medical treatment failed or induces an increase in capillary related interstitial fluid or if said second capillary related interstitial layer thickness is smaller than said first capillary related interstitial layer thickness then said medical treatment induces a decrease in capillary related interstitial fluid or if said second capillary related interstitial layer thickness is approximately equal to said first capillary related interstitial layer thickness then said medical treatment produces no change in capillary related interstitial fluid.

37. The method of claim 36, wherein said medical treatment comprises administration of a drug to said subject.

38. The method of claim 37, wherein said steps (a), (b), and (c) are repeated at predetermined intervals as an assessment of capillary related interstitial fluid balance of said subject over a clinically relevant time period.

39. The method of claim 38, wherein said drug is a cardiovascular agent.

40. The method of claim 38, wherein said drug is a renal agent.

41. The method of claim 36, wherein said medical treatment comprises surgery.

42. The method of claim 41, wherein said steps (a), (b), and (c) are repeated at predetermined intervals as an assessment of capillary related interstitial fluid balance of said subject over a clinically relevant time period.

43. The method of claim 42, wherein said medical treatment further comprises administration of a general anesthetic.

44. The method of claim 36, wherein said medical treatment comprises intubation.

45. The method of claim 44, wherein said steps (a), (b), and (c) are repeated at predetermined intervals as an assessment of capillary related interstitial fluid balance of said subject over a clinically relevant time period.

46. The method of claim 34, wherein said steps (a), (b), and (c) are initiated within 36 hours of a trauma to said subject and an initial capillary related interstitial layer thickness is determined and said steps (a), (b), and (c) are repeated during a clinical relevant time period after said trauma and sequential capillary related interstitial layer thicknesses are determined, wherein a progressive increase in capillary related interstitial layer thickness indicates an increase in capillary related interstitial fluid and a progressive decrease in capillary related interstitial layer thickness indicates a decrease in capillary related interstitial fluid.

47. The method of claim 33, wherein said at least one ultrasound signal is from an ultrasound probe positioned on an epidermal surface of a tissue, wherein positioning permits measurement of an interstitial layer between bone and skin and said subject has been diagnosed as requiring a capillary related interstitial fluid assessment and said ultrasound probe is specifically adapted for capillary related interstitial fluid assessment.

48. The method of claim 47, wherein said probe is positioned, either continuously or intermittently, at approximately the same anatomical site on an epidermal surface of said tissue, and said transmitting and recording occur at clinically relevant time intervals over at least about a 4 hour time period.

49. The method of claim 47, wherein said ultrasound probe is secured to said subject with an adhesive, wherein said adhesive can acoustically couple said ultrasound probe to the skin of said subject.

50. The method of claim 49, wherein said ultrasound probe has a surface area no more than about 2 cm².

51. The method of claim 42, wherein said determining further comprises comparing capillary related interstitial layer thickness with a standard value for capillary related interstitial layer thickness for a particular anatomical region.

52. A method of assessing vascular performance, comprising:

a) reducing or increasing blood flow to a tissue in a subject,

b) monitoring a capillary related interstitial layer thickness of said tissue with an ultrasound probe after or concurrent with said step (a),

c) increasing said blood flow to said tissue after said reducing in step (a) and said monitoring in step (b) or decreasing said blood flow to said tissue after said increasing in step (a) and said monitoring in step (b), and

d) monitoring said capillary related interstitial layer thickness of said tissue with an ultrasound probe, after or concurrent with said step (c),

wherein said reduction in blood flow controllably reduces blood flow to said tissue for a clinically relevant period of time in step (a) and said increase in blood flow controllably increases blood flow to said tissue for a clinically relevant period of time in step (c), or

wherein said increase in blood flow controllably increases blood flow to said tissue for a clinically relevant period of time in step (a) and said reduction in blood flow controllably reduces blood flow to said tissue for a clinically relevant period of time in step (c).

53. The method of claim 52, wherein said tissue is in an appendage and step (a) further comprises applying a tourniquet to said appendage to reduce blood flow to said appendage.

54. The method of claim 53, wherein said ultrasound probe is a part of a B scan ultrasound system.

55. The method of claim 54, wherein said monitoring in either said steps (b) or (d) occurs at, at least one predetermined time.

56. The method of claim 55, wherein said monitoring can detect a 15% change in interstitial layer thickness.

57. The method of claim 56, wherein said appendage is a leg.

58. The method of claim 57, wherein said tissue is located in the pretibial region of said leg.

59. The method of claim 58, wherein said steps (a) through (d) are performed before a medical treatment and either after or concurrent with said medical treatment.

60. The method of claim 59, wherein said medical treatment is the administration of a cardiovascular agent.

61. The method of claim 52, further comprising monitoring a capillary related interstitial layer thickness of said tissue with an ultrasound probe, before said step (a).

62. The method of claim 54, wherein said clinically relevant period is between about five and 90 minutes.

63. The method of claim 55, wherein said monitoring in either said steps (b) or (d) occurs continuously.

64. The method of claim 52, wherein said ultrasound probe is adapted to measure interstitial layer thickness.

65. The method of claim 64, wherein said monitoring in either said steps (b) or (d) occurs during at least one predetermined time.

66. The method of claim 65, wherein said monitoring can detect about a 1% or more change in leg diameter arising from changes in interstitial layer thickness.

67. The method of claim 66, wherein said appendage is a leg and said tissue is located in a tibial region of said leg.

68. The method of claim 67, wherein said increase in blood flow in step (c) occurs with either 1) the tibial region elevated at a level approximately above the heart of said subject, 2) the tibial region at approximately the same level as the heart of said subject or 3) the tibial region located at a level approximately below the heart of said subject.

69. The method of claim 68, wherein the tibial region is located at a level approximately below the heart of said subject and said monitoring detects an increase in capillary related interstitial layer thickness during said reduction in blood flow and said monitoring detects a decrease in capillary related interstitial layer thickness during said increase in blood flow, wherein a less than 50% decrease in capillary related interstitial layer thickness after 60 minutes of said increase in blood flow indicates venous insufficiency.

70. The method of claim 64, wherein said steps (a) through (d) are performed before a medical treatment and either after or concurrent with said medical treatment.

71. The method of claim 70, wherein said medical treatment is the administration of a cardiovascular agent.

72. A method for non-invasively estimating dynamic cardiac performance in a human, comprising:

a) monitoring interstitial fluid content with an ultrasound probe positioned on the skin of a human in need of cardiac performance evaluation and in an anatomical region suitable for monitoring changes in interstitial fluid content during a clinically relevant time period, and

b) comparing said capillary related interstitial fluid content monitored in step (a) with a standard value for capillary related interstitial fluid content or with a measurement of capillary related interstitial fluid content in said human.

73. The method of claim 72, wherein said comparing qualitatively compares interstitial fluid content to a predetermined standard value for interstitial fluid content, wherein said comparison provides a diagnostic measure of cardiac performance.

74. The method of claim 72, wherein said human is suspected of having a medical condition that increases interstitial fluid content.

75. The method of claim 74, wherein monitoring occurs before and after elevating legs of said human.

76. The method of claim 74, wherein said monitoring occurs before and during exercise challenge.

77. The method of claim 74, wherein said monitoring occurs before and after application of a tissue compression appendage stocking.

78. The method of claim 74, wherein said medical condition is abnormally elevated afterload.

79. The method of claim 74, wherein said monitoring occurs before and during administration of a sufficient amount of isotonic saline to cause a temporary interstitial fluid challenge.

80. A method of detecting rapid changes in capillary related interstitial fluid volume in a human, comprising:

a) positioning a first ultrasound probe on a skin surface of a first anatomical region of said human in need of capillary related interstitial fluid volume detection during a clinically relevant time period,

b) interrogating said first anatomical region with ultrasound pulses from said first ultrasound probe, and

c) detecting a first capillary related interstitial fluid volume between an inner surface of skin and either a bone or fat surface in said first anatomical region with ultrasound signals from said ultrasound pulses, wherein said first capillary related interstitial fluid volume is an indicator of capillary related interstitial fluid volume of said first anatomical region or optionally is an indicator of systemic capillary related interstitial fluid volume.

81. The method of claim 80, further comprising the step of comparing said first capillary related interstitial fluid volume to a predetermined value for capillary related interstitial fluid layer volume.

82. The method of claim 81, wherein said anatomical region is selected from the group consisting of a tibial region, a humerus region, a chest region, an abdominal region, and a cranial region.

83. The method of claim 82, wherein said measuring is a quantitative measurement of capillary related interstitial fluid volume comprising determining a capillary related interstitial layer thickness or a capillary related interstitial layer volume.

84. The method of claim 83, wherein said quantitative measurement can detect about a 1 millimeter or greater change in interstitial layer thickness.

85. The method of claim 84, wherein said measuring occurs during at least two predetermined monitoring times or measuring occurs continuously during said clinically relevant time period.

86. The method of claim 85, wherein said measuring occurs over more than a 20 minute time frame.

87. The method of claim 86, wherein said probe remains in approximately the same position during said measuring and said measurements occur no less than 1 per minute at regularly spaced intervals.

88. The method of claim 87, further comprising placing a plurality of probes at different anatomical regions and performing steps (a) through (c) for each anatomical region.

89. The method of claim 88, wherein said plurality of probes comprises a left tibial region probe, and a right tibial region probe, wherein said steps (a) through (c) are performed concurrently with said plurality of probes.

90. The method of claim 89, wherein said plurality of probes further comprises a humerus probe, cranial probe, chest probe, and an abdominal probe.

91. A compact ultrasound probe for in situ ultrasound measurements, comprising:

a) at least one ultrasound crystal in acoustic communication with an acoustic coupling material,

b) an ultrasound crystal holder adapted for securing said acoustic coupling material to a surface of an object or subject for in situ ultrasound measurements, and

c) an electrical coupling for electrically connecting said at least one ultrasound crystal to an ultrasound output or recording system, wherein said electrical coupling is compatible with securing said ultrasound probe for in situ ultrasound measurements.

92. The compact ultrasound probe of claim 91, wherein said at least one ultrasound crystal is a plurality of crystals.

93. The compact ultrasound probe of claim 92, wherein said acoustic coupling material and said ultrasound crystal holder are flexible.

94. The compact ultrasound probe of claim 91, wherein said acoustic coupling material has an adhesive coating or adhesive properties.

95. The compact ultrasound probe of claim 91, wherein said subject is a human and said ultrasound crystal holder is adapted to attach to a securing member that secures an appendage of said human and secures said ultrasound crystal holder, wherein said acoustical coupling material is secured in acoustical contact with said surface and optionally containing an acoustic coupling gel between said surface and said coupling material.

96. The compact ultrasound probe of claim 91, wherein said electrical coupling comprises a light weight wire for transmitting electrical signals to an ultrasound computational unit.

97. The compact ultrasound probe of claim 91, wherein said electrical coupling comprises an infrared coupler to an ultrasound computational unit.

98. The compact ultrasound probe of claim 91, wherein said electrical coupling comprises a radio frequency coupler that transmits signals to an ultrasound computational unit.

99. The compact ultrasound probe of claim 98, wherein said radio frequency coupler receives signals from said ultrasound computational unit.

100. The compact ultrasound probe of claim 96, wherein said coupling material has a surface area of about 2 cm².

101. The compact ultrasound probe of claim 96, wherein said probe is not adapted for Doppler measurements.

102. The compact ultrasound probe of claim 96, wherein said probe is not adapted for positioning on the surface of a body cavity.

103. A screen display comprising a predetermined set of anatomical features that appears on the screen, and at least one processed signal that appears on the screen and corresponds to at least one anatomical feature of said predetermined set of anatomical features.

104. The screen display of claim 103, wherein said predetermined set of anatomical features appears as a simulated image of an anatomical region, said image reflects distances between anatomical features, and at least one distance corresponds to at least one processed signal.

105. The screen display of claim 104, wherein said image comprises an anatomical feature selected from the group of bone, skin, interstitial layer and muscle.

106. The screen display of claim 105, wherein said at least one processed signal is an ultrasound signal.

107. The screen display of claim 106, further comprising at least one image reflecting at least one processed signal previously stored in a storage device.

108. An in situ probe holder comprising a holder member to hold and secure a probe to a surface, wherein said probe is an ultrasound probe, or MRI probe.

109. The in situ probe holder of claim 108, further comprising a plurality of extending members disposed on said holder member to secure said holder member to said surface and said surface is skin and said probe is an ultrasound probe.

110. The in situ probe holder of claim 109, wherein said extending members comprise an adhesive surface.

111. The in situ probe holder of claim 110, wherein said holder member is permanently attached to said extending members, said holder member and said extending members are made of a flexible plastic.

112. The in situ probe holder of claim 109, wherein said holder member and said extending members form a unit that weighs about 30 to 50 grams or less and said unit is sterile and further comprises a covering to protect said unit from contamination.

113. The in situ probe holder of claim 109, wherein disposed on said holder is an adhesive surface to secure said holder to said surface, said surface is a skin, said probe is an ultrasound probe.

114. The in situ probe holder of claim 109, wherein said holder comprises a film to permit acoustic coupling of said ultrasound probe to said skin.

115. The in situ probe holder of claim 109, wherein said holder further comprises an ultrasound micro-transducer.

116. The in situ probe holder of claim 115, wherein said holder is about 3 cm² or less.

121. The micro-transducer of claim 108, wherein said micro-transducer transmits signals to an ultrasound system using infrared or radio frequency signals.

122. The micro-transducer of claim 121, wherein said micro-transducer is sterile and further comprises a covering to protect said unit from contamination.

117. A micro-transducer comprising an acoustic surface acoustically coupled to an ultrasound source, said acoustic surface and said ultrasound source are disposed in a frame adapted for directly or indirectly securing said micro-transducer to a skin.

118. The micro-transducer of claim 117, wherein said micro-transducer is adapted for monitoring interstitial thickness.

119. The micro-transducer of claim 118, wherein said micro-transducer has surface area of about 3 cm² or less.

120. The micro-transducer of claim 119, wherein said micro-transducer is 1 cm or less in thickness.

123. A multi-probe set comprising a first ultrasound probe comprising a first output port, said first ultrasound probe adapted for continuous or in situ monitoring at a first anatomical region and a second ultrasound probe comprising a second output port, said second ultrasound probe adapted for continuous or in situ monitoring at a second anatomical region.

124. The multi-probe set of claim 123, further comprising an ultrasound system to concurrently process first signals from said first ultrasound probe and second signals from said second ultrasound probe.

125. The multi-probe set of claim 123, wherein an anatomical region is selected from the group consisting of the forehead region, anterior tibia region, foot region, distal radius region, elbow region, prestemal region and temporal bone region.

126. The multi-probe set of claim 125, wherein said ultrasound probe is a micro-transducer adapted for monitoring interstitial layer thickness.

127. The multi-probe set of claim 126, further comprising a third ultrasound probe comprising a third output port, said third ultrasound probe adapted for continuous or in situ monitoring at a third anatomical region.

128. A method of multisite monitoring, comprising:

a) transmitting an ultrasound pulse from a first ultrasound probe to a first anatomical region,

b) transmitting an ultrasound pulse from a second ultrasound probe to a second anatomical region,

c) recording ultrasound signals from a first ultrasound probe to a first anatomical region,

d) recording ultrasound signals from a second ultrasound probe to a second anatomical region, and

e) monitoring interstitial layer thickness of said first and second anatomical regions.

129. The method of claim 128, wherein said monitoring from said first anatomical region is concurrent with said monitoring from said second anatomical region.

130. The method of claim 128, wherein said step (a) is within about 10 seconds of step (b) and is automatically controlled by a computational unit.

131. The method of claim 130, wherein said steps (a) through (e) are repeated about every 30 to 600 seconds.

132. The method of claim 131, wherein said first and second ultrasound probes are micro-transducers.

133. The method of claim 132, further comprising a third micro-transducer.

134. The method of claim 131, further comprising a step of comparing interstitial layer thickness from said first and second anatomical regions.

135. The method of claim 131, further comprising a step determining the rate of change over time of an interstitial layer thickness from said first and second anatomical regions.

136. The method of claim 134, wherein said micro-transducers are secured to the skin for continuous monitoring during at least about a 1 to 24 hour period.

137. The method of claim 136, wherein an anatomical region is selected from the group consisting the forehead region, anterior tibia region, distal radius region, presternal region and temporal bone region.

138. The method of claim 134, wherein said micro-transducers are secured to the skin for continuous monitoring during a clinically relevant time period.