QUANTITATIVE MULTI-SPECTRAL OPTO-ACOUSTIC TOMOGRAPHY (MSOT) OF TISSUE BIOMARKERS

• US 20110306857A1
• Filed: 07/25/2008
• Published: 12/15/2011
• Est. Priority Date: 07/25/2008
• Status: Active Grant

• Current Assignee: Helmholtz Zentrum München Deutsches Forschungszentrum für. Gesundheit und Umwelt (GmbH)
• Original Assignee: Helmholtz Zentrum München Deutsches Forschungszentrum für. Gesundheit und Umwelt (GmbH)
• Inventors: Razansky, Daniel, Ntziachristos, Vasilis
• Granted Patent: US 9,572,497 B2
• Time in Patent Office: Days
• US Class Current: 600/317
• 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 5/0095 by applying light and detecting acoustic waves, i.e. photoacoustic measurements

Abstract

A method of multi-spectral opto-acoustic tomography (MSOT) imaging of a target tissue including a target tissue biomarker includes illuminating the target tissue with an illumination device emitting at least one pulsed illumination pattern at several illumination wavelengths, detecting pressure signals from the target tissue biomarker with a detector device, wherein the pressure signals being produced in the target tissue are in response to the illumination, and reconstructing a quantitative tomographic image of a distribution of the target tissue biomarker in the target tissue, wherein the pressure signals are analyzed using a photon propagation model which depends on an illuminating light fluence in the target tissue and on the illumination wavelengths, at least one spectral processing scheme, and an inversion scheme providing the tomographic image.

Claims

1. A method of multi-spectral opto-acoustic tomography (MSOT) imaging of a target tissue including a target tissue biomarker, comprising:

illuminating the target tissue with an illumination device emitting at least one pulsed illumination pattern at several illumination wavelengths;

detecting pressure signals from the target tissue biomarker with a detector device, wherein the pressure signals being produced in the target tissue are in response to the said illumination; and

reconstructing a quantitative tomographic image of a distribution of the target tissue biomarker in the target tissue, wherein the pressure signals are analyzed using

a photon propagation model which depends on an illuminating light fluence in the target tissue and on the illumination wavelengths;

at least one spectral processing scheme; and

an inversion scheme providing the tomographic image.

2. The imaging method according to claim 1, wherein

the illumination pattern includes at least two spectrally distinct wavelength ranges in a time-shared fashion.

3. The imaging method according to claim 1, wherein the photon propagation model is calculated using at least one of the following:

a solution of a photon transport equation, adapted to a geometry of illumination of the target tissue;

an empiric model of photon transport in the target tissue;

a model incorporating incident photon distribution and/or the illumination pattern; and

/or

the detected pressure signals and/or opto-acoustic images produced at any reconstruction stage.

4. The imaging method according to claim 1, wherein

the inversion scheme combines the photon propagation model and an acoustic propagation model in a tomographic reconstruction to yield the quantitative tomographic image.

5. The imaging method according to claim 1, wherein

the inversion scheme combines the photon propagation model and the acoustic propagation model in an iterative fashion.

6. The imaging method according to claim 1, wherein the spectral processing scheme includes at least one of the following:

it is integrated in the inversion scheme;

a processing step on the collected data; and

a processing step on the reconstructed data.

7. The imaging method according to claim 1, wherein one or more of the following applies

the illumination device and the detector device are integrated in a common measuring head unit and the illuminating and detecting steps include positioning the measuring head unit in contact with a target tissue component or matching fluid;

the illumination device is arranged in the target tissue and the detector device is arranged in contact with an outer surface of the target tissue or matching fluid;

the detector device is arranged in the target tissue and the illumination device is arranged outside or in contact with an outer surface of the target tissue;

the illumination device and the detector device are arranged in close proximity or in contact with an outer surface of a target tissue;

or

the detection device measures opto-acoustically induced pressure signals in a non-contact manner.

8. The imaging method according to claim 1, wherein

the illumination device and the acoustic detector device are arranged inside a blood vessel using an intravascular catheter;

or

the measuring head unit of the illumination and detector devices is a hand-held device.

9. The imaging method according to claim 1, wherein

the target tissue includes a light-absorbing reporter to target the biomarker.

10. The imaging method of claim 9, wherein the light-absorbing reporter includes at least one of:

fluorescent or chromophoric molecules;

fluorescent proteins;

noble-metal-containing particles;

super-paramagnetic particles;

carbon particles; and

activatable substrates.

11. The imaging method of claim 9, wherein

the light-absorbing reporter includes steep change in its absorption spectrum.

12. The imaging method of claim 11, wherein

the illumination wavelengths include at least two wavelengths that are differentially absorbed by the target bio-marker.

13. The imaging method according to claim 1, wherein the target tissue biomarker targets at least one of:

a cancer disease;

a cardiovascular disease, in particular including atherosclerotic plaque;

inflammatory disease;

an aspect of disease for diagnostic purposes;

an aspect of disease state; and

an aspect of disease treatment.

14. The imaging method according to claim 1, wherein the target tissue includes at least one of:

tissue of a small animal;

tissue of mesoscopic size;

tissue of at least one human organ.

15. An imaging device adapted for multi-spectral opto-acoustic tomography (MSOT) imaging a target tissue including a target tissue biomarker, comprising:

an illumination device adapted for illuminating the target tissue with at least one pulsed illumination pattern at several illumination wavelengths that are absorbed by the target tissue biomarker;

a detector device that detects pressure signals produced from the target tissue biomarker in the target tissue in response to the said illumination; and

a reconstruction device that reconstructs a quantitative tomographic image of a distribution of the target tissue biomarker in the target tissue, whereas the reconstruction device comprises

a processor adapted for calculating a photon propagation model which depends on the light pattern that illuminates the target tissue and on the illumination wavelengths;

a processor adapted for implementing a spectral processing scheme; and

a processor adapted for implementing an inversion scheme providing the tomographic image.

16. The imaging device according to claim 15, wherein

the illumination device and the detector device are integrated in a common measuring head unit.

17. The imaging device according to claim 16, wherein

the measuring head unit comprises an array of illumination elements and sensor elements.

18. The imaging device according to claim 17, wherein the array includes at least one of:

line-shaped arrangements of the illumination elements and the sensor elements; and

matrix-shaped arrangements with an alternating distribution of the illumination elements and the sensor elements.

19. The imaging device according to claim 15, wherein

the illumination device is illuminates the target tissue along at least two different diffusive projection directions.

20. The imaging device according to claim 15, wherein the illumination device and the acoustic detector device are configured for at least one of

being arranged in a blood vessel, the illumination device including an optical fiber or a light waveguide;

and

provides a contact with an outer surface of the target tissue.

21. The imaging device according to claim 15, wherein

at least one of the illumination device and the detector device is included in an endoscopic, laparoscopic or interstitial device.

22. The imaging device according to claim 15, wherein the reconstruction device applies inverse methods and spectral processing to build an image of a blood vessel comprising a coronary or a carotid artery, wherein the image represents a spatial distribution of the bio-marker in the target tissue.