# US 9,433,351 B2 · Tri modal spectroscopic imaging

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- Number: US 9,433,351 B2
- Document ID: US9433351B2
- Status: Granted
- Kind: B2
- Application number: 13/464,578
- Filed: 2012-05-04
- Published: 2012-10-11
- Granted: 2016-09-06
- Earliest claimed: 2005-07-25
- Assignees: Massachusetts Institute of Technology
- Applicants: Chung-Chieh Yu; Condon Lau; Stephen Fulghum; Christopher Fang-yen; Ramachandra Dasari; Michael Feld; David Feld; Alison Hearn; Jonathan Feld
- Inventors: Chung-Chieh Yu; Condon Lau; Stephen Fulghum; Christopher Fang-yen; Ramachandra Dasari; Michael Feld
- Web page: https://patentgrep.com/patent/US9433351B2

## CPC

- A61B 5/0059: {using light, e.g. diagnosis by transillumination, diascopy, fluorescence (photoacoustic A61B5/0093; optical measurement of heart rate A61B5/02416; optical measurement of blood flow A61B5/0261; optical measurement of analytes A61B5/1455)}
- A61B 5/0066: {Optical coherence imaging}
- G01J 3/02: Details
- G01J 3/0224: {using polarising or depolarising elements}
- G01J 3/0229: {using masks, aperture plates, spatial light modulators or spatial filters, e.g. reflective filters}
- G01J 3/10: Arrangements of light sources specially adapted for spectrometry or colorimetry
- G01J 3/32: Investigating bands of a spectrum in sequence by a single detector
- G01N 21/4738: {Diffuse reflection (precedence is given to G01N21/55 - G01N21/57 if specular component is taken into consideration), e.g. also for testing fluids, fibrous materials}
- G01N 21/49: within a body or fluid
- G01N 2021/4733: {Discriminating different types of scatterers}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to a spectroscopic imaging system using autofluorescence and reflectance images to diagnose tissue. A preferred embodiment of the invention uses a plurality of light sources to illuminate a tissue region to provide the fluorescence and reflectance images, respectively.

## Claims

### Claim 1

A spectroscopic imaging system comprising:
a light source system including a broadband light source and a laser light source for inducing tissue autofluorescence;
an optical scanning system configured to optically couple light from the light source system across a scanning region that is positioned to receive scanning light that is incident on an illumination area within the scanning region, the optical scanning system including a moveable mirror device;
a fiber optic device optically coupling light from the light source system to the optical scanning system, the fiber optic device having a proximal end and a distal end;
an imaging detector optically coupled to a proximal end of the fiber optic device such that the imaging detector detects autofluorescent light and reflectance light to provide autofluorescence image data and reflectance image data;
the moveable mirror device providing relative movement between light emitted from a distal end of the fiber optic device and the scanning region, the optical scanning system optically coupling light received from the scanning region by the moveable mirror device into a plurality of collection optical fibers of the fiber optic device, the proximal end of the plurality of collection optical fibers being optically coupled to the imaging detector for acquiring images of tissue; and
a data processor connected to the imaging detector that processes the autofluorescence image data and reflectance image data to generate a diagnosis.

### Claim 2 (depends on 1)

The system of claim 1 further comprising a mask positioned between the light source system and the scanning region and a plurality of filters to filter collected light.

### Claim 3 (depends on 1)

The system of claim 1 wherein the moveable mirror device is optically coupled to the distal end of the fiber optic device.

### Claim 4 (depends on 3)

The system of claim 3 wherein the movable mirror device comprises a digital micromirror array.

### Claim 5 (depends on 1)

The system of claim 1 further comprising a computer program stored in a memory and operating on the data processor, the computer program processing the autofluorescence image data and the reflectance image data to compute intrinsic autofluorescence data and diffuse reflectance data.

### Claim 6 (depends on 1)

The system of claim 1 wherein the broadband light source comprises a tunable source.

### Claim 7 (depends on 1)

The system of claim 1 wherein a flipping movable mirror switches between the broadband light source and the laser light source.

### Claim 8 (depends on 1)

The system of claim 1 wherein the light source system includes an optical parametric oscillator.

### Claim 9 (depends on 1)

The system of claim 1 further comprising a spatial gate positioned between the scanning region and the imaging detector.

### Claim 10 (depends on 1)

The system of claim 1 further comprising an angular gate positioned between the scanning region and the imaging detector.

### Claim 11 (depends on 1)

The system of claim 1 wherein the data processor determines a size of a cellular structure from a reflectance spectrum.

### Claim 12 (depends on 1)

The system of claim 1 wherein the fiber optic device is optically coupled to an aperture that collects the autofluorescence light and reflectance light.

### Claim 13 (depends on 1)

The system of claim 1 wherein the detector simultaneously detects an area of a region of interest with a two dimensional array of pixel elements such that the scanning system images adjacent regions in sequence.

### Claim 14 (depends on 1)

The system of claim 1 wherein the detector comprises at least a 500×500 array of pixel elements such that the detector generates an image of an area of the scanning region having at least 500×500 image pixels.

### Claim 15 (depends on 1)

The system of claim 1 wherein the system further comprises a polarizer such that the collection optical fibers couple polarized light to the imaging detector.

### Claim 16 (depends on 1)

The system of claim 1 further comprising a polarizer positioned between the scanning region and the imaging detector.

### Claim 17 (depends on 1)

The system of claim 1 further comprising an aperture positioned between the scanning region and the collection optical fibers that separates a polarization component.

### Claim 18 (depends on 1)

The system of claim 1 wherein the light source system emits light at a plurality of different wavelengths that are coupled to the optical scanning system such that the imaging detector detects separate images at each of the plurality of different wavelengths.

### Claim 19 (depends on 18)

The system of claim 18 further comprising a polarizer and an aperture such that at least one polarized light component is coupled to the collection optical fibers.

### Claim 20 (depends on 1)

The system of claim 1 wherein the fiber optic device comprises a plurality of light delivery optical fibers that are optically coupled to the moveable mirror device that simultaneously scans different regions of tissue with a plurality of light spots.

### Claim 21 (depends on 1)

The system of claim 1 wherein the fiber optic device comprises illumination optical fibers and the plurality of collection optical fibers.

### Claim 22

A spectroscopic imaging system comprising:
a light source system including a broadband light source and a laser light source for inducing tissue autofluorescence;
an optical scanning system that is configured to optically couple scanning light from the light source system across a scanning spot pattern, the optical scanning system including a moveable mirror device;
a fiber optic device optically connecting the light source system to the optical scanning system;
an imaging detector optically coupled to a proximal end of the fiber optic device such that the imaging detector detects autofluorescent light and reflectance light to provide autofluorescence image data and reflectance image data;
the moveable mirror device providing relative movement between light emitted from a distal end of the fiber optic device and a scanning region defined by an illumination area of the scanning spot pattern to simultaneously deliver a plurality of separated light spots that are scanned across the scanning region, the moveable mirror device optically coupling received light from the scanning region into a plurality of collection optical fibers of the fiber optic device, a proximal end of the collection optical fibers being optically coupled to the imaging detector to acquire images; and
a data processor connected to the imaging detector that processes the autofluorescence image data and reflectance image data to generate a diagnosis.

### Claim 23 (depends on 22)

The system of claim 22 wherein the moveable mirror device is optically coupled to a distal end of the collection optical fibers.

### Claim 24 (depends on 22)

The system of claim 22 further comprising a computer program stored in a memory and operating on the data processor, the computer program processing the autofluorescence image data and the reflectance image data to compute intrinsic autofluorescence data and diffuse reflectance data to generate a diagnosis of a cancerous condition.

### Claim 25 (depends on 22)

The system of claim 22 further comprising a spatial gate or an angular gate positioned in an optical path between the moveable mirror device and the collection optical fibers that are coupled to the imaging detector.

### Claim 26 (depends on 22)

The system of claim 22 wherein the fiber optic device further comprises a plurality of spaced illumination optical fibers to couple light spots to the scanning optical system.

### Claim 27 (depends on 22)

The system of claim 22 wherein the fiber optic device further comprises a plurality of illumination fibers that are optically coupled to the moveable mirror device wherein the scanning region is configured with a plurality of illumination areas such that each respective light spot is smaller than an area illuminated by each respective light spot, the scanning spot pattern defined by a line of spots.

### Claim 28 (depends on 22)

The system of claim 22 further comprising a phantom having scatterers and fluorophores, the phantom being illuminated with light from the light source system such that light from the phantom is detected with the imaging detector and wherein the data processor processes the detected light to determine an illumination unit area of the scanning region.
