Systems and methods for recording simultaneously visible light image and infrared light image from fluorophores

Patent metadata

Field	Value
Publication number	US-12324559-B2
Application number	US-202318223390-A
Country	US
Kind code	B2
Filing date	Jul 18, 2023
Priority date	Apr 23, 2013
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

The invention provides systems and methods for imaging a sample. In various embodiments, the invention provides a system comprising an image sensor, a laser for emitting excitation light for an infrared or near-infrared fluorophore, a visible light source, a notch beam splitter, a notch filter, a synchronization module, an image processing unit, an image displaying unit, and light-conducting channels. In various embodiments, the present invention provides a system comprising an image sensor, a laser for emitting excitation light for an infrared or near-infrared fluorophore, a laser clean-up filter, a notch filter, a white light source, an image processing unit, an image displaying unit, and light-conducting channels. In accordance with the present invention, the image sensor can detect both visible light and infrared light.

First claim

The invention claimed is:

1. An imaging system for imaging a sample comprising an infrared or near-infrared fluorophore, comprising:
an image sensor;
a laser to emit an excitation light for the infrared or near-infrared fluorophore, wherein the excitation light excites the infrared or near-infrared fluorophore in the sample to emit an emission light;
a notch filter in an emission light path from the sample to the image sensor, wherein the notch filter blocks a portion of the excitation light reflected from the sample towards the image sensor;
a notch beam splitter in the light path from the laser to the sample, whereby the excitation light is reflected by the notch beam splitter to the sample;
a white light source to emit a light comprising visible light, wherein the visible light is conducted to the sample, wherein the sample reflects the visible light, wherein the reflected visible light is conducted to the image sensor;
wherein the white light source, the laser, or both are pulsed; and
an image processing unit to process signals from the image sensor to generate a white light frame (WLF) when the sample receives only visible light, a stray light frame (SLF) when the same receives neither visible light nor the excitation light, and two or more near infrared frames (NIFs) when the sample receives only the excitation light to reduce a ghosting effect.

2. The imaging system of claim 1 , wherein the image sensor is synchronized to an on and off status of the laser.

3. The imaging system of claim 1 , wherein the image sensor is a CCD image sensor or a CMOS image sensor.

4. The imaging system of claim 1 , wherein the image sensor comprises one or more image sensors.

5. The imaging system of claim 1 , wherein the image sensor is a single image sensor.

6. The imaging system of claim 5 , wherein the single image sensor is configured to detect both the emission light and the visible light from the sample and configured to generate sensor signals, and wherein the image sensor comprises blue, green and red pixel sensors.

7. The imaging system of claim 1 , wherein the excitation light comprises light having a wavelength of about 749-789 or 775-795 nm.

8. The imaging system of claim 1 , wherein the notch filter selectively blocks light having a wavelength of about 749-789, 770-800, 765-805, or 760-810 nm.

9. The imaging system of claim 1 , further comprising a notch beam splitter that reflects light having a wavelength of about 700, 725, or 750 nm.

10. The imaging system of claim 1 , wherein the image processing unit generates the WLF from a first frame, the SLF from a second frame captured after the first frame, and the NIF from a third frame captured after the second frame.

11. The imaging system of claim 10 , wherein the image processing unit generates the NIF from the third frame, a fourth frame captured after the third frame, and a fifth frame captured after the fourth frame.

12. The imaging system of claim 1 , wherein the image processing unit generates the image frame by adding together two subsequent sets of the first frame, the second frame, the third frame, the fourth frame, and the fifth frame.

13. The imaging system of claim 10 , wherein the image processing unit subtracts the SLF from each NIF and then adds together all SLF-subtracted NIFs to generate a final NIF.

14. The imaging system of claim 13 , wherein the image processing unit false colors the final NIF.

15. The imaging system of claim 14 , wherein the image processing unit adds the false colored final NIF to the WLF to generate a composite image frame of visible light and infrared light.

16. The imaging system of claim 1 , further comprising an image displaying unit to display images based on the image frames generated from the image processing unit, wherein the image displaying unit is connected to the image processing unit.

17. The imaging system of claim 1 , wherein the excitation light from the laser is conducted to the sample through one or more channels, and/or wherein the visible light from the white light source is conducted to the sample through one or more channels, and/or wherein the emission light emitted from the sample is conducted to the image sensor through one or more channels, and/or wherein the visible light reflected from the sample is conducted to the image sensor through one or more channels.

18. The imaging system of claim 1 , wherein the excitation light is conducted to the sample along an emission light path in a first direction within a first channel.

19. The imaging system of claim 18 , wherein the emission light is conducted to the image sensor along the emission light path in a second direction opposite the first direction and overlapping at least partially within the first channel.

20. The imaging system of claim 19 , wherein the visible light from the white light source is conducted to the sample through a third channel, wherein the emission light emitted from the sample is conducted to the single image sensor through the second channel, and wherein the visible light reflected from the sample is conducted to the single image sensor through a fourth channel.

21. The imaging system of claim 20 , wherein the first, second, third, and fourth channels are four separate channels or combined into one, two, or three channels.

22. The imaging system of claim 1 ,
wherein the excitation light from the laser is further conducted to the sample through a third light channel housed in an endoscope;
wherein the visible light from the white light source is conducted to the sample through a fourth light channel housed in the endoscope; and
wherein the image sensor is housed in the endoscope at or near the patient end of the endoscope.

23. The imaging system of claim 22 , wherein the third light channel, the fourth light channel, or both, is an optical cable.

24. The imaging system of claim 22 , further comprising one or more lenses in the emission light path and/or the visible light path from the sample to the image sensor, wherein the one or more lenses are located at or near the patient end of the endoscope.

25. The imaging system of claim 1 , wherein there is no infrared filter in the emission light path from the sample to the single image sensor.

26. The imaging system of claim 1 , wherein there is no Fabry-Perot etalon, Raman analysis filter wheel, dispersive element, dispersive prism, isosceles prism, diffraction grating, reflection-type diffraction grating, or transmission-type diffraction grating in the emission light path from the sample to the image sensor.

27. The imaging system of claim 1 , wherein the emission light is not dispersed or filtered for Raman band selection in the emission light path from the sample to the image sensor.

28. The imaging system of claim 1 , wherein the image sensor is configured not to detect Raman scattered light from the sample.

29. The imaging system of claim 1 , wherein the infrared or near-infrared fluorophore is any one or more of indocyanine green (ICG), a functional equivalent of ICG, an analog of ICG, a derivative of ICG, a salt of ICG, IR800, Alexa680, cy5.5, a functional equivalent of IR800, a functional equivalent of Alexa680, a functional equivalent of cy5.5, an analog of IR800, an analog of Alexa680, an analog of cy5.5, a derivative of IR800, a derivative of Alexa680, a derivative of cy5.5, a salt of IR800, a sa

Assignees

• Cedars Sinai Medical Center

Inventors

• Butte Pramod
• Mamelak Adam

Classifications

• G06T7/0012

  Biomedical image inspection · CPC title

• G01N2021/6463

  Optics · CPC title

• G01N21/6456

  Spatial resolved fluorescence measurements; Imaging · CPC title

• H04N25/131

  including elements passing infrared wavelengths · CPC title

• H04N23/21

  from near infrared [NIR] radiation · CPC title