In-vivo optical imaging method including analysis of dynamic images

• US 9,220,411 B2
• Filed: 05/31/2007
• Issued: 12/29/2015
• Est. Priority Date: 06/01/2006
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Hillman, Elizabeth M.C.
• Primary Examiner(s): EVOY, NICHOLAS LANE
• Application Number:
  US12/302,986
• Publication Number:
  US 20090252682A1
• Time in Patent Office: 3,134 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 2503/40 Animals
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61K 49/0017 Fluorescence in vivo

Abstract

In-vivo optical molecular imaging methods for producing an image of an animal are described. A time series of image data sets of an optical contrast substance in the animal is acquired using an optical detector Each image data set is obtained at a selected time and has the same plurality of pixels, with each pixel having an associated value. The image data sets are analyzed to identify a plurality of distinctive time courses, and respective pixel sets are determined from the plurality of pixels which correspond to each of the time courses. In one embodiment, each pixel set is associated with an identified anatomical or other structure, and an anatomical image map of the animal can be generated which includes one or more of the anatomical structures.

Claims

1. An in-vivo optical molecular imaging method for producing an image of an animal, comprising:

acquiring, from an animal positioned on an imaging platform, a time series of image data sets of a targeted optical contrast substance within the animal, the time series obtained by taking a plurality of images at distinct times following introduction of the contrast substance into the animal, using an optical detector, wherein each image data set is obtained at a selected time and has the same plurality of pixels, with each pixel having an associated value for each time in the time series, the imaging platform having a surface for supporting the subject in a desired arrangement in a field of view of an optical detector operable to acquire an image of a subject within the field of view,

and wherein at least one mirror is arranged at an angle with respect to the imaging platform surface such that multiple views of the subject are within the field of view of the optical detector, and

wherein a processor is configured to process image data received from the optical detector;

determining a plurality of distinctive time courses based on the image data sets,

analyzing the image data sets to separate, for each pixel of a plurality of pixels, the associated values into a plurality of components, each of which is associated with one of the time courses, and

generating an image of the animal wherein the value at each pixel of the generated image corresponds to the value of the component associated with a single time course,

wherein time courses are (T_org1(t), T_org2(t), . . .) and the time courses are used in a linear non-negative least-squares fit to image time series data M(r,t) to resolve spatial distribution of pixels r with t time course (I_org1(r), I_org2(r), by solving;

2. The method of claim 1, wherein the optical contrast substance is a dye.

3. The method of claim 1, wherein the analyzing step includes a principal component analysis.

4. The method of claim 1, wherein the analyzing step includes using a plurality of basis time courses in a least squares determination of a matrix equation relating the image data sets to the basis time courses.

5. The method of claim 1, further including determining autofluorescent effects and subtracting the autofluorescent effects to generate the image of the animal.

6. The method of claim 1, wherein a field of view of the optical detector includes multiple views of the animal.

7. The method of claim 1, wherein the step of acquiring a time series of image data sets comprises acquiring a time series of image data sets of a plurality of targeted optical contrast substances.

8. The method of claim 1, wherein the step of determining a plurality of time courses includes using pixel values from multiple time points within the time series, and the generating step further comprises calculating a single spatial distribution of the pixel values across the time series.

9. The method of claim 1, wherein the step of analyzing the image data sets is achieved using pixel values obtained at a plurality of time points within the time series such that the plurality of time courses are identified based on calculated spatial and temporal patterns of emission from the optical contrast substance.

10. The method of claim 1, wherein the step of determining a plurality of time courses is a calculation based on the temporal pattern of emission of the optical contrast substance at each pixel.

11. The method of claim 1, wherein the optical contrast substance within the animal are used to identify multiple organs within a single image.

12. The method of claim 1, wherein the method further includes:

associating at least one respective pixel set with a physiological process.

13. The method of claim 1, wherein the optical contrast substance in the animal separates targeted optical contrast substance wash-out from targeted optical contrast substance uptake.

14. The method of claim 1, wherein the determining step is performed based on the time series of image data sets obtained from the animal.

15. The method of claim 1, wherein the determining step is performed based on a time series of image data sets obtained from an animal that is different from the animal to be imaged.

16. An in-vivo optical molecular imaging method for localizing a targeted region with respect to anatomical structures of an animal, comprising:

positioning the animal on an imaging platform having a surface for supporting the subject in a desired arrangement in a field of view of an optical detector operable to acquire an image of a subject within the field of view,

wherein at least one mirror is arranged at an angle with respect to the imaging platform surface such that multiple views of the subject are within the field of view of the optical detector, and

wherein a processor is configured to process image data received from the optical detector;

acquiring a targeted image data set of a first dye using the optical detector while the animal is in the desired arrangement, the targeted image data set having a plurality of pixels,

acquiring a time series of anatomical image data sets of a second dye using the optical detector while the animal is in the same desired arrangement, the time series obtained by taking a plurality of images at distinct times following introduction of the contrast substance into the animal, each anatomical image data set obtained at a selected time and having a same plurality of pixels as the others, each pixel having an associated value for each time in the series,

determining a plurality of distinctive time courses based on the dynamics of the image data sets of the second dye in the animal,

analyzing the anatomical image data sets to separate, for each pixel of a plurality of pixels, the associated values into a plurality of components, each of which is associated with one of the time courses, and associating each time course with an identified anatomical structure,

generating an anatomical image map of the animal which includes each anatomical structure as a differentiated pixel set, and

combining the targeted image data set with the anatomical image map to generate an image representative of the animal showing the location of the targeted region with respect to the anatomical structures,

wherein time courses are (T_org1(t), T_org2(t), . . .) and the time courses are used in a linear non-negative least-squares fit to image time series data M(r,t) to resolve spatial distribution of pixels r with t time course (I_org1(r), I_org2(r), by solving;

17. The method of claim 16 wherein the acquiring steps include the use of optical filters to distinguish between the first dye and the second dye.

18. The method of claim 16, wherein the analyzing step includes using a plurality of basis time courses in a least squares determination of a matrix equation relating the anatomical image data sets to the basis time courses to determine a pixel set corresponding to each of the plurality of basis time courses, and to identify specific anatomical structures corresponding to each pixel set.

19. An imaging system, comprising:

an optical detector which is operable to acquire an image of a subject within a field of view;

an imaging platform having a surface for supporting the subject in a desired arrangement;

at least one mirror arranged at an angle with respect to the imaging platform surface such that multiple views of the subject are within the field of view of the optical detector,

a processor configured to process image data received from the optical detector, and

a machine-readable medium that includes instructions executable by the processor, the instructions including

acquiring a time series of image data sets of a targeted optical contrast substance within the subject using the optical detector, the time series obtained by taking a plurality of images at distinct times following introduction of the contrast substance into the animal, and wherein each image data set is obtained at a selected time and has the same plurality of pixels, with each pixel having an associated value for each time in the time series,

determining a plurality of distinctive time courses based on the image data sets,

analyzing the image data sets to separate, for each pixel of a plurality of pixels, the associated values into a plurality of components, each of which is associated with one of the time courses, and

generating an image of the subject wherein the value at each pixel of the generated image corresponds to the value of the component associated with a single time course, and

wherein time courses are (T_org1(t), T_org2(t), . . .) and the time courses are used in a linear non-negative least-squares fit to image time series data M(r,t) to resolve spatial distribution of pixels r with t time course (I_org1(r), I_org2(r), by solving;

20. The imaging system of claim 19, wherein two mirrors are arranged at an angle with respect to the imaging platform surface.

21. The imaging system of claim 19, wherein each mirror is arranged at a forty five degree angle with respect to the imaging platform surface.

22. An in-vivo optical molecular imaging method for producing an image of an animal, comprising:

acquiring, from an animal positioned on an imaging platform, a time series of image data sets of a targeted optical contrast substance within the animal, the time series obtained by taking a plurality of images at distinct times following introduction of the contrast substance into the animal, using an optical detector, wherein each image data set is obtained at a selected time and has the same plurality of pixels, with each pixel having an associated value for each time in the time series, the imaging platform having a surface for supporting the subject in a desired arrangement in a field of view of an optical detector operable to acquire an image of a subject within the field of view,

and wherein at least one mirror is arranged at an angle with respect to the imaging platform surface such that multiple views of the subject are within the field of view of the optical detector, and

wherein a processor is configured to process image data received from the optical detector;

determining a plurality of distinctive time courses based on the image data sets,

analyzing the image data sets to separate, for each pixel of a plurality of pixels, the associated values into a plurality of components, each of which is associated with one of the time courses, and

generating an image of the animal wherein the value at each pixel of the generated image corresponds to the value of the component associated with a single time course,

and, after the determining steps and the analyzing steps, generating an anatomical image map of the animal which includes each anatomical structure as a differentiated pixel set, and

combining the targeted image data set with the anatomical image map to generate an image representative of the animal showing the location of the targeted region with respect to the anatomical structures,

wherein the steps of acquiring, determining, analyzing and generating are performed on a machine-readable medium that includes instructions executable by the processor.