Method and apparatus for determining autofluorescence of skin tissue

• US 7,966,060 B2
• Filed: 01/29/2004
• Issued: 06/21/2011
• Est. Priority Date: 09/30/1999
• Status: Expired due to Fees

• Current Assignee: DiagnOptics Holding B.V.
• Original Assignee: DiagnOptics Holding B.V.
• Inventors: Graaff, Reindert, Smit, Andries Jan, Oomen, Petrus Hendricus N., Jager, Jan
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/767,147
• Publication Number:
  US 20040186363A1
• Time in Patent Office: 2,700 Days
• Field of Search: 600/317, 600/407, 600/473, 600/476, 600/310
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/441 Skin evaluation, e.g. for skin disorder diagnosis
• CPC Class Codes: A61B 5/444 Evaluating skin marks, e.g. mole, nevi, tumour, scar

Abstract

For determining autofluorescence of a clinically normal skin issue (7) of a patient, the tissue (7) is irradiated with electromagnetic radiation. An amount of fluorescent radiation emitted by the tissue (7) in response to the irradiation is measured and, in response thereto, a signal is generated which represents a determined autofluorescence in agreement with the measured amount of electromagnetic radiation. Because the tissue (7) is skin tissue (7) in vivo and irradiation is performed noninvasively, a method which is very simple to apply for determining autofluorescence is obtained. An apparatus especially adapted for use in this method is also described.

Claims

1. A method for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

using a radiation source to irradiate said skin tissue with electromagnetic excitation radiation;

receiving and measuring an amount of electromagnetic, fluorescent radiation emitted by said skin tissue in response to said irradiation; and

generating, in response to said measured amount of fluorescent radiation, a signal which represents said measured amount of fluorescent radiation; and

determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and outputting said determined advanced glycation/glycosylation end product content;

wherein said skin tissue is non-locally anomalous, intact skin tissue in vivo which is irradiated noninvasively and simultaneously in its entirety by directing said radiation from said radiation source to a portion of the outer surface of the skin, wherein fluorescent radiation emitted in response to said irradiation is simultaneously received from a surface area of the irradiated portions of the skin surface of at least 1 cm², wherein said fluorescent radiation is received via a measuring window; and

wherein said measuring window is oriented at an angle of 25-65°

relative to the irradiated portion of the surface of the skin.

2. A method for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

using a radiation source to irradiate said skin tissue with electromagnetic excitation radiation;

receiving and measuring an amount of electromagnetic, fluorescent radiation emitted by said skin tissue in response to said irradiation; and

generating, in response to said measured amount of fluorescent radiation, a signal which represents said measured amount of fluorescent radiation; and

determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and outputting said determined advanced glycation/glycosylation end product content;

wherein said skin tissue is non-locally anomalous, intact skin tissue in vivo which is irradiated noninvasively and simultaneously in its entirety by directing said radiation from said radiation source to a portion of the outer surface of the skin, wherein fluorescent radiation emitted in response to said irradiation is simultaneously received from a surface area of the irradiated portions of the skin surface of at least 1 cm², wherein a supporting structure is held against the skin of the individual, wherein the irradiated skin tissue area is located behind an opening in the supporting structure, wherein the supporting structure supports a measuring window, wherein said fluorescent radiation is received via said measuring window and wherein said measuring window is held at a distance from the skin.

3. An apparatus for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

a pick-up unit with;

a radiation source, for in vivo and noninvasively irradiating a surface portion of intact skin tissue behind an irradiation window with electromagnetic excitation radiation; and

a detector for measuring an amount of electromagnetic fluorescent radiation received from only a portion of said irradiated skin surface portion;

circuitry connected to said pick-up unit for generating an autofluorescence value for said non-locally anomalous, intact skin tissue in agreement with the measured amount of fluorescent radiation, for determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and for outputting said determined advanced glycation/glycosylation end product content; and

a measuring window bounding a surface area for passing fluorescent radiation to be detected from said portion of the skin surface from which said amount of fluorescent radiation is received to the detector, said portion of the skin surface from which said amount of fluorescent radiation is received being larger than the surface area bounded by said measuring window.

4. An apparatus according to claim 3, wherein said portion of the skin surface from which said amount of fluorescent radiation is received is at least three times larger than the surface area of said measuring window.

5. An apparatus for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

a pick-up unit with;

a radiation source, for in vivo and noninvasively irradiating intact skin tissue behind an irradiation window with electromagnetic excitation radiation by directing said radiation from said radiation source to a portion to be irradiated of the outer skin surface; and

a detector for measuring an amount of electromagnetic fluorescent radiation simultaneously received from a surface area of the irradiated portion of the skin surface of at least 1 cm²; and

circuitry connected to said pick-up unit for generating an autofluorescence value for said non-locally anomalous, intact skin tissue in agreement with the measured amount of fluorescent radiation originating from said surface area of said skin tissue, for determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and for outputting said determined advanced glycation/glycosylation end product content, further comprising a supporting structure to beheld against the skin of the individual, for defining a plane in which a surface portion of said skin tissue to be irradiated is located, wherein the supporting structure supports a measuring window for passing light to be detected originating from said irradiated skin tissue, said measuring window being oriented at an angle of 25-65°

relative to said plane and located for receiving radiation emitted from the skin in a direction at an angle to the direction of the excitation radiation.

6. An apparatus according to claim 5, wherein said supporting structure comprises the irradiation window, said measuring window being located adjacent an edge of said irradiation window.

7. An apparatus for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

a pick-up unit with;

a radiation source, for in vivo and noninvasively irradiating intact skin tissue behind an irradiation window with electromagnetic excitation radiation by directing said radiation from said radiation source to a portion to be irradiated of the outer skin surface; and

a detector for measuring an amount of electromagnetic fluorescent radiation simultaneously received from a surface area of the irradiated portion of the skin surface of at least 1 cm²; and

circuitry connected to said pick-up unit for generating an autofluorescence value for said non-locally anomalous, intact skin tissue in agreement with the measured amount of fluorescent radiation originating from said surface area of said skin tissue, for determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and for outputting said determined advanced glycation/glycosylation end product content, further comprising a supporting structure to be held against the skin of the individual, for defining a plane in which a surface of said skin tissue to be irradiated is located behind an opening in the supporting structure, wherein the supporting structure supports a measuring window for passing light to be detected originating from said irradiated skin tissue, wherein said measuring window is spaced away from said plane.

8. A method for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

using a radiation source to irradiate said skin tissue with electromagnetic excitation radiation;

receiving and measuring an amount of electromagnetic, fluorescent radiation emitted by said skin tissue in response to said irradiation; and

generating, in response to said measured amount of fluorescent radiation, a signal which represents said measured amount of fluorescent radiation; and

determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and outputting said determined advanced glycation/glycosylation end product content;

wherein said irradiated skin tissue is non-locally anomalous, intact skin tissue in vivo which is irradiated noninvasively and simultaneously in its entirety by directing said radiation from said radiation source to a portion of the outer surface of the skin, wherein the measured fluorescent radiation emitted in response to said irradiation is simultaneously received from only a portion of said irradiated portion of said skin surface.

9. A method according to claim 8, wherein the measured fluorescent radiation is received via a measuring window bounding a surface area, and wherein said portion of the irradiated portion of the skin surface from which the measured fluorescent radiation is received has a surface area larger than the surface area bounded by said measuring window.

10. A method according to claim 9, wherein the surface area of the skin from which the measured fluorescent radiation is received is at least three times larger than the surface area bounded by said measuring window.

11. A method according to claim 8, wherein the measured fluorescent radiation has one or more wavelengths larger than 420 nm.

12. A method according to claim 8, wherein the size of the portion of the irradiated skin surface portion from which the measured fluorescent radiation is received is at least 1 cm².

13. A method according to claim 8, wherein the fluorescent radiation emitted in response to said irradiation is simultaneously received from a surface area of the irradiated portion of the skin surface larger than 0.1 cm².

14. An apparatus for determining an advanced glycation/glycosylation end product content of non-locally anomalous, intact skin tissue of a human individual, comprising:

a pick-up unit with;

a radiation source, for in vivo and noninvasively irradiating intact skin tissue behind an irradiation window by directing electromagnetic excitation radiation from said radiation source to a portion of the outer skin surface behind the irradiation window; and

a detector for measuring an amount of electromagnetic fluorescent radiation emitted in response to said irradiation received simultaneously from only a portion of said irradiated skin surface portion; and

circuitry connected to said pick-up unit for generating an autofluorescence value for said non-locally anomalous, intact skin tissue in agreement with a measured amount of fluorescent radiation originating from said portion of said irradiated portion of said skin surface, for determining an advanced glycation/glycosylation end product content of said skin tissue from said signal, and for outputting said determined advanced glycation/glycosylation end product content.

15. An apparatus according to claim 14, wherein the detector is arranged for measuring electromagnetic fluorescent radiation received from a surface area of said portion of said irradiated skin surface portion of at least 1 cm².

16. An apparatus according to claim 14, wherein the surface area of the irradiated portion of the skin surface from which the fluorescent radiation emitted in response to said irradiation can be received simultaneously is larger than 0.1 cm².

17. A method for determining an advanced glycation/glycosylation end product content for a human individual, comprising:

irradiating skin tissue of said individual with electromagnetic excitation radiation;

receiving and measuring an amount of electromagnetic, fluorescent radiation emitted by said material in response to said irradiation; and

generating, in response to said measured amount of fluorescent radiation, a signal which represents a determined advanced glycation/glycosylation end product content for said individual;

wherein said skin tissue is non-locally anomalous, intact skin tissue in vivo of which a surface is irradiated noninvasively and simultaneously in its entirety;

wherein fluorescent radiation emitted in a direction at an angle to the direction of the excitation radiation is simultaneously received from different portions of the skin surface;

wherein said fluorescent radiation is received via a measuring window; and

wherein said measuring window is oriented at an angle of 25-65°

relative to the irradiated surface of the skin.

18. A method for determining an advanced glycation/glycosylation end product content for a human individual, comprising:

irradiating skin tissue of said individual with electromagnetic excitation radiation via an opening in a surface contacting the skin;

receiving and measuring an amount of electromagnetic, fluorescent radiation emitted by said material in response to said irradiation; and

generating, in response to said measured amount of fluorescent radiation, a signal which represents a determined advanced glycation/glycosylation end product content for said individual;

wherein said skin tissue is non-locally anomalous, intact skin tissue in vivo of which a surface is irradiated noninvasively and simultaneously in its entirety;

wherein fluorescent radiation emitted in response to said irradiation is simultaneously received from different portions of the skin surface; and

wherein said fluorescent radiation is received via a measuring window and wherein said measuring window is held at a distance from the skin.

19. An apparatus for determining an advanced glycation/glycosylation end product content for a human individual, comprising:

a pick-up unit with;

a radiation source, for in vivo and noninvasively irradiating a surface of non-locally anomalous, intact skin tissue with electromagnetic excitation radiation via an irradiation window for delimiting a surface portion of said skin tissue to be irradiated; and

a detector for measuring an amount of electromagnetic fluorescent radiation received from a surface area of said skin tissue in a direction at an angle to the direction of the excitation radiation;

circuitry connected to said pick-up unit for generating a value representing a determined advanced glycation/glycosylation end product content for said individual in agreement with the measured amount of fluorescent radiation originating from said surface area of said skin tissue; and

a supporting structure to be held against the skin of the individual, for defining a plane in which a surface portion of said skin tissue to be irradiated is located;

wherein the supporting structure supports a measuring window for passing light to be detected from said irradiated skin tissue, said measuring window being oriented at an angle of 25-65°

relative to said plane.

20. An apparatus for determining an advanced glycation/glycosylation end product content for a human individual, comprising:

a pick-up unit with;

a radiation source, for in vivo and noninvasively irradiating a surface of non-locally anomalous, intact skin tissue behind an irradiation window with electromagnetic excitation radiation in a direction perpendicular to the skin; and

a detector for measuring an amount of electromagnetic fluorescent radiation received from a surface area of said skin tissue;

circuitry connected to said pick-up unit for generating a value representing a determined advanced glycation/glycosylation end product content for said individual in agreement with the measured amount of fluorescent radiation originating from said surface area of said skin tissue; and

a supporting structure to be held against a skin of the individual, for defining a plane in which said surface of said skin tissue to be irradiated is located behind an opening in the supporting structure, wherein the supporting structure supports a measuring window for passing light to be detected coming from said irradiated skin tissue, wherein said measuring window is spaced away from said plane.