Method and apparatus for non-invasive detection of angiogenic and anti-angiogenic activity in living tissue

• US 6,701,171 B2
• Filed: 02/08/2001
• Issued: 03/02/2004
• Est. Priority Date: 03/31/2000
• Status: Expired due to Fees

• Current Assignee: Københavns Universitet
• Original Assignee: Kbenhavns Universitet
• Inventors: Quistorff, Bjørn, Kragh, Michael, Kristjansen, Paul E. G.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/778,923
• Publication Number:
  US 20010035503A1
• Time in Patent Office: 1,118 Days
• Field of Search: 600/310, 600/322, 600/323, 600/326, 600/328, 600/481, 600/483, 600/500, 600/504
• US Class Current: 600/328
• 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 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: G01N 2021/4747 Concentric bundles
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

The present invention relates to a method for non-invasive local quantification of angiogenesis or destruction of existing blood vessels in living tissue, the use of the said method for local measurements of hemoglobin concentration and blood perfusion at the same location on the subject and an apparatus for carrying out the method according to the invention. The apparatus comprises a xenon flash unit, an optical filter and a Y-shaped optical fiber-bundle, one branch of the fiber-bundle being coupled to the flash unit and the other branch of the fiber-bundle being coupled to a detection unit and the merged part of the fiber-bundle being adapted to couple the apparatus to the tissue to be tested.

Claims

1. An apparatus for non-invasive local determination of blood vessel formation in living tissue comprising

a xenon flash unit,

an optical filter,

a Y-shaped optical fiber-bundle, one branch of the fiber-bundle being coupled to the flash unit and the other branch of the fiber-bundle being coupled to the detection unit, and the merged part of the fiber-bundle being adapted to couple the apparatus to the tissue to be tested, and

a laser Doppler flowmeter.

2. The apparatus according to claim 1, wherein the light absorption detection unit comprises a photo-diode and amplifier, a sample and hold circuit and A/D converter, and a micro controller for controlling the frequency of the measurements, said micro controller being connected to a PC for evaluating and displaying the measurement results.

3. The apparatus according to claim 1, wherein an optical filter is placed in front of the detection unit, said filter being an interference type filter (800 nm +/−

10 nm), with a collecting lens forming the light guide image on the photodiode.

4. A non-invasive method for local determination of blood vessel formation of a subject, which comprises

(i) measuring the total hemoglobin concentration of the subject using near infrared spectroscopy, and substantially at the same time;

(ii) measuring average blood perfusion using laser Doppler flowmetry,

wherein the two measurements (i) and (ii) are performed at substantially the same position on the subject.

5. The method according to claim 4, wherein the near infrared spectroscopy measurement and the laser Doppler flowmetry measurement are performed with the same probe.

6. The method according to claim 5, wherein the agent that affects blood circulation comprises at least one an anti-angiogenic agent, vascular targeting agent, and/or anti-inflammatory agent.

7. The method according to claim 4, wherein the steps (i) and (ii) are performed after administration to the subject of an agent that affects blood circulation.

8. The method according to claim 4, wherein the steps (i) and (ii) are performed on a skin transplant.

9. The method according to claim 4, wherein the steps (i) and (ii) are performed repeatedly during an extended time period.