ACOUSTIC-ASSISTED ITERATIVE WAVE FORM OPTIMIZATION FOR DEEP TISSUE FOCUSING

• US 20120070817A1
• Filed: 09/20/2011
• Published: 03/22/2012
• Est. Priority Date: 09/20/2010
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Wang, Ying Min, Yang, Changhuei
• Granted Patent: US 10,292,589 B2
• Time in Patent Office: Days
• US Class Current: 435/3
• 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: G01N 2021/1727 Magnetomodulation
• CPC Class Codes: G01N 2021/4709 Backscatter
• CPC Class Codes: G01N 21/1717 with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
• CPC Class Codes: G01N 21/47 Scattering, i.e. diffuse reflection G01N21/25, G01N21/41 take precedence G01N21/55 takes precedence
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

A method, apparatus, and article of manufacture for irradiating one or more targets within a sample with electromagnetic (EM) radiation. One or more targets within the sample are controllably defined with an acoustic field. The sample is irradiated with input EM radiation having an input wavefront. An amount of frequency shifted EM radiation is detected, wherein at least some of the input EM radiation that passes through the acoustic field at the targets is shifted in frequency to form the frequency shifted EM radiation. The input wavefront is modified, using feedback comprising the amount of the frequency shifted EM radiation that is detected, into a modified wavefront. The sample is irradiated using the input EM radiation comprising the modified wavefront, and the process is repeated as desired.

Claims

1. A method for irradiating a target within a sample, comprising:

(a) controllably defining a target within a sample with an acoustic field;

(b) irradiating the sample with input Electromagnetic (EM) radiation having an input wavefront;

(c) detecting an amount of frequency shifted EM radiation, wherein at least some of the input EM radiation that passes through the acoustic field at the target is shifted in frequency by the acoustic field to form the frequency shifted EM radiation;

(d) modifying the input wavefront, using feedback comprising the amount of the frequency shifted EM radiation that is detected, into a modified wavefront; and

(e) repeating step (b) using the modified wavefront as the input wavefront.

2. The method of claim 1, further comprising repeating steps (a)-(e) until a threshold intensity or desired focus of the input EM radiation at the target is achieved, wherein the modifying comprises selecting the modified wavefront that maintains, increases, or maximizes the amount of the frequency shifted EM radiation as compared to the amount of the frequency shifted EM radiation obtained using the input wavefront.

3. The method of claim 1, wherein the acoustic field is focused to produce a first focus of the acoustic field at the target, and the modified wavefront converges to form a second focus of the input EM radiation at the target.

4. The method of claim 1, wherein the acoustic field comprises ultrasound.

5. The method of claim 1, further comprising using the input EM radiation comprising the modified wavefront to perform Raman spectroscopy of the target.

6. The method of claim 1, wherein the irradiating of the sample includes selecting a frequency of the input EM radiation that enables multi-photon excitation of the target.

7. The method of claim 1, wherein the sample is tissue, and the input EM radiation does not damage tissue that is not at the target.

8. The method of claim 7, further comprising using the input EM radiation comprising the modified wavefront to cut the tissue at, and defined by, the target, wherein the target is at a depth of at least 1 mm from a surface of the tissue.

9. The method of claim 7, wherein:

the acoustic field comprises ultrasound that is focused to an ultrasound focal spot at the target,

the ultrasound focal spot has a diameter of 100 micrometers or less at a depth of at least 5 mm within the tissue, and

the input EM radiation is focused to at most a same size as the ultrasound focal spot.

10. The method of claim 7, further comprising performing photodynamic therapy on the tissue, wherein the input EM radiation having the modified wavefront excites a photosensitive agent at the target to trigger the photodynamic therapy of the tissue at the target.

11. An apparatus implementing the method of claim 1.

13. The apparatus of claim 11, further comprising one or more controllers for:

(1) instructing the EM radiation source and control system to irradiate the sample with the input EM radiation having the input wavefront,

(2) receiving the amount of the frequency shifted EM radiation from the detection system,

(3) controlling how the wavefront modifying device modifies the input wavefront into the modified wavefront using the feedback, wherein the modified wavefront is used as the input wavefront, and

(4) repeating functions (1)-(3) sequentially until a threshold intensity or desired focus of the input EM radiation at the target is achieved, wherein the one or more controllers select the modified wavefront that maintains, increases, or maximizes the amount of the frequency shifted EM radiation as compared to the amount of the frequency shifted EM radiation obtained using the input wavefront.

14. The apparatus of claim 11, wherein the acoustic wave source and control system focuses acoustic waves to produce a first focus of the acoustic field at the target, and the modified wavefront converges to form a second focus of the input EM radiation at the target.

15. The apparatus of claim 11, wherein the acoustic wave generator and control system comprises an ultrasound transducer, wherein the acoustic field comprises ultrasound.

16. The apparatus of claim 11, wherein the apparatus is optically coupled to a Raman spectroscopy system, wherein the input EM radiation having the modified wavefront is used to perform Raman spectroscopy of the target.

17. The apparatus of claim 11, wherein the EM radiation source and control system is irradiates the sample with the input EM radiation having a frequency that enables multi-photon excitation of the target.

18. The apparatus of claim 11, further comprising a sample holder for the sample that is tissue, wherein the sample holder is:

adjustably positioned relative to the EM radiation source and control system,

adjustably positioned relative to the acoustic wave source and control system, and

radiatively coupled to the detection system, and wherein the EM radiation source and control system irradiates the tissue with the input EM radiation that does not damage tissue that is not at the target.

19. The apparatus of claim 17, wherein:

the sample holder is adjustably positioned relative to the acoustic wave source and control system, and the EM radiation source and control system, to cut the tissue at the target, and

the target is at a depth of at least 1 mm from a surface of the tissue.

20. The apparatus of claim 17, wherein:

the acoustic wave source and control system comprises an ultrasound transducer that generates the acoustic field comprising ultrasound that is focused to an ultrasound focus at the target,

the ultrasound focal spots have a diameter of 100 micrometers or less at a depth of at least 5 mm within the tissue, and

the input EM radiation is focused to at most a same size as the ultrasound focal spot.

21. The apparatus of claim 17, wherein the apparatus is part of a photodynamic therapy system and the input EM radiation comprising the modified wavefront excites one or more photosensitive agents at the target to trigger photodynamic therapy of the tissue defined by the target.

12. An apparatus for irradiating a target within a sample, comprising:

(a) an acoustic wave source and control system for transmitting an acoustic field that controllably defines a target within the sample;

(b) an EM radiation source and control system for irradiating the sample with input Electromagnetic (EM) radiation having an input wavefront;

(c) a detection system for detecting an amount of the frequency shifted EM radiation, wherein at least some of the input EM radiation that passes through the acoustic field at the target is shifted in frequency by the acoustic field to form the frequency shifted EM radiation;

(d) a wavefront modifying device for modifying the input wavefront, using feedback comprising the amount of the frequency shifted EM radiation that is detected, into a modified wavefront; and

(e) wherein the modified wavefront is used as the input wavefront.

22. A method for irradiating a target within a sample with electromagnetic (EM) radiation, comprising:

(a) transmitting one or more fields into a sample to controllably define a target within the sample, wherein the fields are scattered less than the EM radiation;

(b) irradiating the sample with input EM radiation having an input wavefront;

(c) detecting an amount of feedback EM radiation, wherein at least some of the input EM radiation that passes through the fields at the target interacts with the fields to form the feedback EM radiation; and

(d) modifying the input wavefront, using feedback comprising an amount of the feedback EM radiation that is detected, into a modified wavefront; and

(e) repeating step (b) using the modified wavefront as the input wavefront.