THz sensing of corneal tissue water content

Patent metadata

Field	Value
Publication number	US-10939844-B2
Application number	US-201716093953-A
Country	US
Kind code	B2
Filing date	Apr 17, 2017
Priority date	Apr 15, 2016
Publication date	Mar 9, 2021
Grant date	Mar 9, 2021

Abstract

Methods and apparatus for corneal imaging and sensing are provided. Apparatus capable of utilizing single or multiple frequency emissions at terahertz (THz) wavelengths to create reflectivity maps of the cornea in either a contact or non-contact modes are also provided. Methods of obtaining data from THz imaging and sensing apparatus about the corneal tissue-aqueous humor system, including information about the corneal tissue water content (CTWC) and/or the central corneal thickness (CCT) are likewise provided. Methodologies may use multiple transfer functions (frequencies) in obtaining simultaneous data about CTWC and CCT. Methods using frequency sweeping to allow for determination of CTWC and CCT may also be utilized. Methods may also be used to assess CTWC using multiple bandwidths at the same frequency, or multiple frequencies at the same bandwidth. Methods may use data from CTWC measurements to aid in the diagnosis of various corneal and brain disorders.

First claim

The invention claimed is:

1. A method for the THz imaging a cornea comprising:
generating an illumination beam having a frequency that is variable about at least one central wavelength greater than 0.1 THz;
illuminating a cornea with the illumination beam at multiple frequencies to produce a plurality of reflected signals therefrom, wherein the multiple frequencies are accomplished by frequency sweeping, using multiple bandwidths at a single frequency, or using multiple frequencies at a single bandwidth;
detecting the plurality of reflected signals across a spectrum of frequencies; and
combining the plurality of reflected signals to obtain a plurality of reflectivity maps of the cornea, said reflectivity maps having a combined signal variation indicative of at least the corneal total water content and central corneal thickness.

2. The method of claim 1 , wherein the illumination beam has a variable bandwidth configured such that both narrowband and broadband illumination beams may be generated.

3. The method of claim 2 , wherein one or both the frequency and bandwidth of the illumination beam may be varied during the illumination.

4. The method of claim 3 , wherein the frequency is swept between about 0.1 and about 1 THz, and wherein the bandwidth of the illumination beam may have a Q of between about 5 and 50.

5. The method of claim 1 , wherein at least two illumination beams are generated, at least one millimeter wave illumination beam having a central frequency less 0.5 THz and at least one THz illumination beam having a central frequency greater than 0.5 THz, and wherein the at least one millimeter wave illumination beam generates a measurement of the central corneal thickness, and wherein the at least one THz illumination beam generates a reflectivity map of the corneal total water content.

6. The method of claim 1 , wherein the reflectivity maps are further correlated with a separately obtained spatially resolved thickness map.

7. The method of claim 1 , wherein the reflectivity map elucidates the nature of the tissue water content gradient of the cornea, and wherein the tissue water content gradient corresponds to a model tissue water content gradient selected from the group of pinned back, pinned front and global.

8. The method of claim 7 , wherein determining the tissue water content gradient is further used to diagnose at least one corneal disorder.

9. The method of claim 8 , wherein the disorder is selected from the group consisting of Fuchs' endothelial dystrophy, keratoconus, pseudophakic bullous keratopathy, graft rejection, and brain trauma.

10. The method of claim 1 , wherein the method generates simultaneous corneal total water content and central corneal thickness using parameters of the cornea determined a priori.

11. The method of claim 1 , wherein the cornea is field-flattened prior to illumination.

12. A THz cornea sensing apparatus comprising:
an emission source configured to generate an illumination beam having a frequency that is variable about at least one central wavelength greater than 0.1 THz;
a detector configured to receive and record a THz signal across a spectrum of frequencies;
one or more transmission optics disposed in optical alignment between the emission source and a target cornea, and configured such that the transmission optics directs the illumination beam to impinge upon a target area on the surface of the cornea, and gathers a reflected THz signal from the target cornea and transmits the reflected THz signal to the detector; and
an analyzer for using a plurality of reflected THz signals obtained at a plurality of illumination beam frequencies to produce a plurality of reflectivity maps of the cornea, said plurality of illumination beam frequencies being accomplished by frequency sweeping, using multiple bandwidths at a single frequency, or using multiple frequencies at a single bandwidth, and said reflectivity maps having a combined signal variation indicative of at least the corneal total water content and central corneal thickness.

13. The apparatus of claim 12 , wherein the apparatus is configured to generate an illumination beam having a variable bandwidth configured such that both narrowband and broadband illumination beams may be generated.

14. The apparatus of claim 13 , wherein one or both the frequency and bandwidth of the illumination beam may be varied.

15. The apparatus of claim 14 , wherein the frequency may be varied between about 0.1 and about 1 THz, and wherein the bandwidth of the illumination beam may have a Q of between about 5 and 50.

16. The apparatus of claim 12 , wherein the apparatus is configured to generate at least two illumination beams, at least one millimeter wave illumination beam having a central frequency less 0.5 THz and at least one THz illumination beam having a central frequency greater than 0.5 THz, and wherein the at least one millimeter wave illumination beam generates a measurement of the central corneal thickness, and wherein the at least one THz illumination beam generates a reflectivity map of the corneal total water content.

17. The apparatus of claim 12 , wherein the analyzer is configured to correlate the reflectivity maps with a separately obtained spatially resolved thickness map.

18. The apparatus of claim 12 , wherein the cornea is field-flattened prior to illumination using a dielectric window transparent to the illumination beam.

19. The apparatus of claim 12 , wherein the transmission optics at least comprise at least two 90° off-axis parabolic mirrors arranged in an angled tip-to-tip geometry.

20. The apparatus of claim 12 , wherein:
the illumination beam is collimated;
the transmission optics includes at least one off-axis parabolic mirror, and at least one scanning mirror;
wherein the center of curvature of the cornea is approximately coincident with the focal point of the off-axis parabolic mirror, and wherein the collimated illumination beam is reflected from off-axis parabolic mirror onto the cornea;
wherein the reflected signal is recollimated by the off-axis parabolic mirror; and
wherein the collimated illumination beam is reflected off the scanning mirror and onto the off-axis parabolic mirror, and wherein the scanning mirror is configured to alter the transverse location of the collimated illumination beam on the off-axis parabolic mirror, such that the target area of the surface of the cornea illuminated by the collimated illumination beam is concomitantly altered, and the reflectivity map of the cornea is obtained without field-flattening.

21. The apparatus of claim 20 , wherein the scanning mirror maintains a parallel path of the collimated illumination beam relative to the clear normal of the off-axis parabolic mirror during alteration of the transverse location.

22. The apparatus of claim 20 , further comprising at least two scanning mirrors having axes that are mutually orthogonal, wherein a first scanning mirror controls the azimuthal location of the collimated illumination beam, and a second scanning mirror alters the elevation location of the collimated illumination beam.

23. The apparatus of claim 20 , wherein the radius of the collimated illumination beam is varied dependent of the incident location of the beam on the off-axis parabolic mirror.

24. The apparatus of claim 20 , further comprising:
a second off-axis parabolic mirror disposed within a beam path of the collimated illumination beam in a symmetric tip to t

Assignees

• Univ California

Inventors

• Grundfest Warren S
• Taylor Zachary
• Garritano James
• Nowroozi Bryan
• Bajwa Neha
• Sung Shijun

Classifications

• A61B5/0507 Primary

  using microwaves or terahertz waves · CPC title

• A61B3/0025

  characterised by electronic signal processing, e.g. eye models · CPC title

• A61B3/1025

  for confocal scanning · CPC title

• G01B11/24

  for measuring contours or curvatures · CPC title

• A61B3/1005

  for measuring distances inside the eye, e.g. thickness of the cornea (A61B3/11 takes precedence) · CPC title