# US 10,945,656 B2 · Device and method for imaging collagen structure in vivo

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,945,656 B2
- Document ID: US10945656B2
- Status: Granted
- Kind: B2
- Application number: 14/780,907
- Filed: 2014-04-04
- Published: 2016-03-10
- Granted: 2021-03-16
- Earliest claimed: 2013-04-05
- Assignees: University of Massachusetts
- Applicants: The University of Massachusetts
- Inventors: Anna N. Yaroslavsky; Xin Feng
- Web page: https://patentgrep.com/patent/US10945656B2

## CPC

- A61B 5/443: {Evaluating skin constituents, e.g. elastin, melanin, water}
- A61B 5/0071: {by measuring fluorescence emission}
- A61B 5/0077: {Devices for viewing the surface of the body, e.g. camera, magnifying lens}
- A61B 5/0082: {adapted for particular medical purposes}
- A61B 5/4848: {Monitoring or testing the effects of treatment, e.g. of medication}
- A61B 5/7271: {Specific aspects of physiological measurement analysis (specific diagnostics methods using bioelectric or biomagnetic signals A61B5/316)}
- A61B 5/6835: {Supports or holders, e.g., articulated arms}
- A61B 2560/0475: Special features of memory means, e.g. removable memory cards
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

The present invention relates to systems and methods or wide-field polarized imaging of the skin. Preferred embodiments of the invention provide quantitative characterization of collagen structures in the skin and can be used to monitor skin treatment. A preferred embodiment can comprise a handheld imaging device that generates polarized images at different depths beneath a dermal surface and a data processor to process image data.

## Claims

### Claim 1

A method for imaging and evaluating collagen structure in a region of tissue of a patient in vivo without staining in real time, the method comprising the steps of:
illuminating a region of skin in vivo on a patient with light, the region having a surface area defined by an imaging aperture;
detecting cross polarized images of light reflected by the region of tissue with a detector separated at a distance from a skin surface, the detector generating image data representing a first depth and a second depth at respective first and second discrete illumination wavelengths in which the collagen structure appears, wherein the second depth is deeper than the first depth and a difference between the first and second wavelengths is at least 10 nm;
evaluating the image data to select only one of the first or second wavelengths of the light in which the collagen structure appears in the respective image data;
processing, by a data processor, the image data in which the collagen structure appears with reference data to determine at least one quantitative characteristic selected from reflectivity, content, density and bundle size of the collagen structure in the region of tissue;
forming and presenting, by the data processor, a chart of the at least one quantitative characteristic on a display; and
evaluating the region of tissue by review of the chart of the at least one quantitative characteristic.

### Claim 2 (depends on 1)

The method of claim 1 further comprising illuminating the imaging aperture having an imaging area of at least 1 cm2, the imaging area being illuminated with light from a light source.

### Claim 3 (depends on 1)

The method of claim 1 further comprising detecting a plurality of images at different wavelengths in a range of 390 nm to 730 nm.

### Claim 4 (depends on 1)

The method of claim 1 further comprising performing a laser treatment on the region of the tissue of the patient and re-imaging the region after the laser treatment to evaluate the laser treatment.

### Claim 5 (depends on 1)

The method of claim 1 further comprising detecting a cross-polarized image of the region of tissue and determining a collagen distribution with the data processor and presenting a chart of the collagen distribution.

### Claim 6 (depends on 1)

The method of claim 1 further comprising determining a change in collagen distribution as a function of time from a plurality of images of a region of interest of a patient collected at a corresponding plurality of different times.

### Claim 7 (depends on 1)

The method of claim 1 further comprising determining a change in reflectivity of the tissue and computing, by the data processor, a change in collagen distribution after treatment.

### Claim 8 (depends on 1)

The method of claim 1 wherein the reference data includes an optical property of skin comparable to skin of the patient.

### Claim 9 (depends on 1)

The method of claim 1 wherein the reference data is generated by having a calibrated reflectance standard in the field of view during imaging for calibrating and normalizing the image data, and the image data is compared with other image data.

### Claim 10 (depends on 1)

The method of claim 1 wherein the second depth is beneath a dermal surface of the region of tissue in a range of 50 to 200 microns.

### Claim 11 (depends on 1)

The method of claim 1 further comprising manually holding hand-held housing relative to the tissue of the patient, the housing including a detector and an illuminator: and a polarizer that polarizes the illuminating light.

### Claim 12 (depends on 11)

The method of claim 11 further comprising illuminating with the illuminator that comprises an annular LED array.

### Claim 13 (depends on 1)

The method of claim 1 further comprising processing image data with the data processor, applying a threshold to the image data, determining a normalized percentage collagen area as a function of time, and presenting the normalized percentage of collagen as a chart.

### Claim 14 (depends on 13)

The method of claim 13 further comprising determining a normalized average pixel value of the image data for an age group and skin type comparable to an age and skin type of the patient.

### Claim 15

A device for imaging a region of tissue without staining in real time comprising:
a housing including an imaging detector;
a light source to illuminate the region of tissue in vivo on a patient with light, the region having a surface area defined by an imaging aperture;
a polarizing element that generates a cross polarized image component that is detected with the detector and output as image data at a first depth and a second depth at respective first and second discrete illumination wavelengths in which the collagen structure appears, wherein the second depth is deeper than the first depth and a difference between the first and second wavelengths is at least 10 nm, the collagen structure appearing in the image data in only one of the first or second wavelengths; and
a data processor connected to the detector that processes the image data in which the collagen structure appears by normalizing brightness of the image data for comparison between different patients or different images and, with reference data, to determine at least one quantitative characteristic selected from reflectivity, content, density and bundle size of the collagen structure in the region of tissue,
wherein the data processor computes a collagen density distribution in the tissue and presents a chart of the collagen density distribution for evaluation.

### Claim 16 (depends on 15)

The device of claim 15 wherein the housing comprises a hand-held assembly including the light source, the optical aperture and the polarizing element and the data processor generates quantitative data regarding collagen distribution in the tissue and further comprising a memory for storing images at different depths within the tissue.

### Claim 17 (depends on 15)

The device of claim 15 further comprising an optical aperture having an area providing a field of view of at least 1 cm2 for each image.

### Claim 18 (depends on 15)

The device of claim 15 wherein the light source comprises a ring illuminator and the light source illuminates the tissue with at least the first and second discrete illumination wavelengths to image tissue at the first depth and the second depth, respectively, under the tissue surface.

### Claim 19 (depends on 15)

The device of claim 15 wherein the light source illuminates a region on the tissue surface to image an area of at least 2 cm2.

### Claim 20 (depends on 15)

The device of claim 15 wherein the light source illuminates a region on the tissue surface to image an area of at least 4 cm2.

### Claim 21 (depends on 15)

The device of claim 15 further comprising a computer program stored on a non-transitory computer readable medium to process image data.

### Claim 22 (depends on 15)

The device of claim 15 further comprising a light source system that illuminates the tissue at a plurality of wavelengths between 390 nm to 730 nm at different times.

### Claim 23 (depends on 15)

The device of claim 15 wherein the data processor applies a threshold to the image data and determines a percentage of collagen area.

### Claim 24 (depends on 15)

The device of claim 15 wherein the data processor determines a normalized pixel value for the image data.

### Claim 25

A device for imaging a region of tissue in vivo without staining in real time comprising:
a housing including an imaging detector, a light source to illuminate the region of tissue;
a polarizing element that generates a cross polarized image of a depth in the range of 50 to 200 microns in the region, the cross polarized image being detected by the imaging detector and output as image data at a first depth and a second depth at respective first and second discrete illumination wavelengths in which the collagen structure appears, wherein the second depth is deeper than the first depth and a difference between the first and second wavelengths is at least 10 nm, the collagen structure appearing in the image data in only one of the first or second wavelengths: and
a data processor receiving the image data in which the collagen structure appears, wherein the data processor is operative to:
calculate absolute reflectance of each single pixel of the field of view: and quantify the collagen structure based upon the absolute reflectance of the pixels, wherein the region of tissue includes a calibrated reflectance standard and the data processor is further operative to calibrate and normalize the image data with the calibrated reflectance standard in a field of view of the imaging detector, and processes the image data in which the collagen structure appears with reference data to determine at least one quantitative characteristic selected from reflectivity, content, density and bundle size of the collagen structure in the region of tissue;
wherein the data processor presents a chart of the at least one quantitative characteristic for evaluation.

### Claim 26 (depends on 25)

A device as recited in claim 25, wherein the data processor is further operative to calculate a percentage of collagen in the region.

### Claim 27 (depends on 25)

A device as recited in claim 25, wherein the data processor is further operative to calculate and display a normalized full width at half maximum (FWHM) of a histogram of the reflectance for evaluation of health of the region.

### Claim 28 (depends on 25)

A device as recited in claim 25, wherein the data processor is further operative to obtain fluorescence images to evaluate distribution of tissue components.