Continuous monitoring of tumor hypoxia using near-infrared spectroscopy and tomography with a photonic mixer device

• US 9,907,495 B2
• Filed: 08/28/2017
• Issued: 03/06/2018
• Est. Priority Date: 04/14/2016
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Belthangady, Chinmay, Kashif, Faisal, Lee, Seung Ah, Troy, Tamara, Perreault, John D., Alla, Suresh
• Primary Examiner(s): STAFIRA, MICHAEL PATRICK
• Application Number:
  US15/688,559
• Publication Number:
  US 20170354359A1
• Time in Patent Office: 190 Days
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• CPC Class Codes: A61B 5/0022 Monitoring a patient using a global network, e.g. telephone networks, internet
• CPC Class Codes: A61B 5/0073 by tomography, i.e. reconstruction of 3D images from 2D projections A61B5/0066 takes precedence
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: G16H 40/67 for remote operation
• CPC Class Codes: H04N 25/71 Charge-coupled device [CCD] sensors; Charge-transfer registers specially adapted for CCD sensors
• CPC Class Codes: H04N 25/76 Addressed sensors, e.g. MOS or CMOS sensors
• CPC Class Codes: H04N 5/33 Transforming infrared radiation cameras or camera modules for generating image signals from infrared radiation H04N23/20; circuitry of SSIS for transforming infrared radiation into image signals H04N25/20

Abstract

A device and a method to measure the concentrations of oxygenated and deoxygenated hemoglobin in tissue around a tumor via near-infrared (NIR) spectroscopy with a photonic mixer device (PMD) is described.

Claims

1. A method for continuous monitoring of tumor hypoxia, the method comprising:

illuminating a tissue region having a tumor with an amplitude modulated near-infrared light source provided in close proximity to the tumor;

recording light reflected from the tissue region using a multi-pixel PMD camera chip provided in close proximity to the tumor, wherein the near-infrared light source is horizontally separated from the PMD camera chip;

measuring amplitude and phase shift of the reflected light;

calculating absorption and reduced scattering coefficients using the amplitude and phase shift of the reflected light;

repeating steps a-d for at least two different wavelengths of light; and

calculating the concentrations of oxygenated and deoxygenated hemoglobin in the tissue region using the absorption and reduced scattering coefficients calculated for the at least two different wavelengths of light.

2. The method of claim 1, wherein the tissue region is illuminated with multiple near-infrared light sources arranged around the PMD camera chip.

3. The method of claim 2, wherein the multiple infrared light sources are operated in a multiplexed fashion such that the amplitude &

phase shift for each light source is recorded separately.

4. The method of claim 1, wherein a first wavelength of the at least two wavelengths of light is above the isosbestic point of hemoglobin and a second wavelength of the at least two wavelengths of light is below the isosbestic point of hemoglobin.

5. The method of claim 4, wherein the first wavelength is about 780 nm and the second wavelength is about 830 nm.

6. The method of claim 1, wherein the near-infrared light source is modulated at a frequency in the 10-1000 MHz range.

7. The method of claim 6, wherein the near-infrared light source is modulated at a frequency of 30 MHz.

8. The method of claim 6, wherein the near-infrared light source is modulated at a frequency of 200 MHz.

9. The method of claim 1, where the amplitude and phase shift values are wirelessly transmitted to a cloud server for calculating the absorption and reduced scattering coefficients and the concentrations of oxygenated and deoxygenated hemoglobin.

10. The method of claim 1, wherein the modulated near-infrared light source and the PMD camera chip are positioned at a distance approximately twice the depth of the tumor from the surface of the tissue region.

11. The method of claim 1, wherein the near-infrared light source and the PMD camera chip are wirelessly powered.

12. The method of claim 1, wherein the near-infrared light source is rotated around the PMD camera chip.