Multi-excitation diagnostic system and methods for classification of tissue
Methods and systems for in vivo classification of tissue are disclosed. The tissue is irradiated with light from multiple light sources and light scattered and fluoresced from the tissue is received. Distinct emissions of the sample are identified from the received light. An excitation emission matrix is generated ( 1002 ). On-diagonal and off diagonal components of the excitation emission matrix are identified ( 1004, 1006, 1008 ). Spectroscopic measures are derived from the excitation emission matrix ( 1014 ), and are compared to a database of known spectra ( 1016 ) permitting the tissue to be classified as benign or malignant ( 1018 ). An optical biopsy needle or an optical probe may be used to contemporaneously classify and sample tissue for pathological confirmation of diagnosis.
1. An optical biopsy needle device comprising:
an elongate biopsy needle having a distal end with a distal tip, said distal end having a tissue collecting cavity proximal to the distal tip and configured to biopsy tissue adjacent the cavity; and
a fiber optic bundle comprising at least one transmitter fiber having a first end extending from the distal tip and having a second end configured to connect to a spectral analysis device, said transmitter fiber configured for transmitting radiation from the spectral analysis device to the distal tip of the biopsy needle, and at least one receiver fiber having a first end extending to the distal tip and having a second end configured to connect to the spectral analysis device, said receiver fiber configured for transmitting radiation from the distal tip of the biopsy needle to the spectral analysis device, wherein the fiber optic bundle extends within the biopsy needle and wherein the first ends of both the transmitter fiber and the receiver fiber terminate at the distal end at the distal tip of the biopsy needle such that the transmitting fiber transmits radiation from the spectral analysis device to the tissue adjacent the distal tip and such that the receiver fiber transmits radiation from the tissue adjacent the distal tip to the spectral analysis device; wherein at least one of:
the tissue collecting cavity is at the distal tip of the biopsy needle and the distal tip of the biopsy needle forms a flat surface; and
each of the first ends of the at least one transmitting fiber and at least one receiving fiber is flush with and exposed within the distal tip.
2. The optical biopsy needle device of claim 1 , wherein the distal tip of the biopsy needle forms a flat surface and wherein the flat surface forms an angle with respect to an axial length of the biopsy needle.
3. The optical biopsy needle device of claim 1 , wherein the distal end of the at least one transmitting fiber is separated by a distance from the distal end of the at least one receiving fiber wherein the distance is measured along the flat surface.
4. The optical biopsy needle device of claim 1 , wherein the biopsy needle is housed within an outer sheath.
5. A method of obtaining a biopsy of tissue comprising
providing an optical biopsy needle device comprising an elongate biopsy needle having a distal end with a distal tip, said distal end configured to biopsy tissue spaced proximally from the distal tip, said device having a fiber optic bundle comprising at least one transmitter fiber for transmitting radiation to the distal tip and at least one receiver fiber for transmitting radiation from the distal tip, wherein the fiber optic bundle including the transmitter fiber and including the receiver fiber extends within the biopsy needle and wherein the fiber optic bundle including the transmitter fiber and including the receiver fiber each terminate at the distal tip of the biopsy needle such that the transmitter fiber transmits radiation to the tissue adjacent the distal tip and such that the receiver fiber transmits radiation from the tissue adjacent the distal tip;
connecting the fiber optic bundle of the optical biopsy needle device to a spectral analysis device;
positioning the distal tip of the biopsy needle adjacent to or within the tissue;
obtaining a spectral response associated with a distinct position of the tissue spaced proximally from the distal tip;
evaluating the spectral response with the spectral analysis device to determine whether the tissue is benign or malignant; and
actuating the biopsy needle device to obtain a portion of tissue spaced proximally from the distal tip at the distinct position and removing the portion of the tissue if the tissue is determined to be malignant.
6. The method of claim 5 further comprising delivering a therapeutic treatment to tissue at the distinct position determined to be malignant.
7. The method of claim 5 , wherein the obtaining operation further comprises
illuminating the tissue with an incident broadband light source;
illuminating the tissue with at least one bandwidth-limited incident light source in the UV and near UC spectrum; and
collecting reflected and emitted light from the tissue.
8. The method of claim 5 , wherein the obtaining operation further comprises
transmitting an excitation signal through the at least one transmitter fiber; and
receiving a fluorescence emission signal through the at least one receiver fiber.
9. The method of claim 8 wherein the evaluating operation determines whether the fluorescence emission signal is indicative of an abnormal level of an endogenous fluorophore in the tissue.
10. The method of claim 9 , wherein the tissue is prostatic tissue and the evaluating operation determines whether the fluorescence emission signal is indicative of a level of tryptophan.
11. The method of claim 9 , wherein the tissue is prostatic tissue and the evaluating operation determines whether the fluorescence emission signal is indicative of a level of NADH.
12. The method of claim 5 , wherein the obtaining operation further comprises
transmitting an excitation signal through the at least one transmitter fiber; and
receiving an elastic scattering signal through the at least one receiver fiber.
13. The method of claim 5 , wherein the evaluating operation further comprises analyzing the spectral response within an artificial neural network trained to differentiate between benign and malignant tissue to determine a morphology of each distinct position.
14. A system for determining morphology of tissue comprising:
a light source;
a spectrometer;
an elongate biopsy needle having a distal end with a distal tip, said distal end having a tissue collecting cavity proximal to the distal tip and configured to biopsy tissue adjacent the cavity;
a fiber optic bundle comprising at least one transmitter fiber having a first end extending from the distal tip and having a second end configured to connect to the spectrometer, said transmitter fiber configured for transmitting radiation from the spectrometer to the distal tip of the biopsy needle, and at least one receiver fiber having a first end extending to the distal tip and having a second end configured to connect to the spectrometer, said receiver fiber configured for transmitting radiation from the distal tip of the biopsy needle to the spectrometer, wherein the fiber optic bundle extends within the biopsy needle and wherein the first ends of both the transmitter fiber and the receiver fiber terminate at the distal end at the distal tip of the biopsy needle such that the transmitting fiber transmits radiation from the spectrometer to the tissue adjacent the distal tip and such that the receiver fiber transmits radiation from the tissue adjacent the distal tip to the spectrometer;
a detector coupled with the spectrometer that translates optical spectral data from the spectrometer into digital data;
a computer including a processor and memory that is coupled with and controls each of the light source, the spectrometer, and the detector;
a module stored in the memory and executed by the processor, wherein the module is trained to analyze the digital data corresponding to the optical spectral data to differentiate the tissue between benign and malignant.
15. The system of claim 14 , wherein the light source further comprises an excitation unit comprising
an input port for receiving commands from the computer;
control circuitry for performing the commands received from the computer;
a broadband light source actuated by the control circuitry;
at least one bandwidth-limited incident light source in the UV and near UV spectrum; and
at least one lens aligned with each of the light sources for focusing light emitted from each of the light sources and transmitting the light to the at least one transmitting optical fiber.
16. The system of claim 14 further comprising a user interface wherein a user may direct operation of the computer.
17. The system of claim 14 further comprising a display for viewing results of the analysis.
18. The method of claim 5 , wherein
the distal tip of the biopsy needle forms a flat surface; and
each of the distal ends of the at least one transmitting fiber and at least one receiving fiber is flush with and exposed within the flat surface.
19. The method of claim 18 , wherein the flat surface forms an angle with respect to an axial length of the biopsy needle.
20. The method of claim 18 , wherein the distal end of the at least one transmitting fiber is separated by a distance from the distal end of the at least one receiving fiber wherein the distance is measured along the flat surface.
21. The optical biopsy needle device of claim 5 , wherein the biopsy needle is housed within an outer sheath.
22. The system of claim 14 , wherein
the distal tip of the biopsy needle forms a flat surface; and
each of the first ends of the at least one transmitting fiber and at least one receiving fiber is flush with and exposed within the flat surface.
23. The system of claim 22 , wherein the flat surface forms an angle with respect to an axial length of the biopsy needle.
24. The system of claim 22 , wherein the distal end of the at least one transmitting fiber is separated by a distance from the distal end of the at least one receiving fiber wherein the distance is measured along the flat surface.
25. The system of claim 14 , wherein the biopsy needle is housed within an outer sheath.
26. The optical biopsy needle device of claim 1 wherein the tissue collecting cavity is at the distal tip of the biopsy needle and the distal tip of the biopsy needle forms a flat surface.
27. The optical biopsy needle device of claim 26 wherein each of the first ends of the at least one transmitting fiber and at least one receiving fiber is flush with and exposed within the flat surface.
28. The optical biopsy needle device of claim 1 wherein each of the first ends of the at least one transmitting fiber and at least one receiving fiber is flush with and exposed within the distal tip.