Systems and methods for path length selected diffuse correlation spectroscopy

Abstract

Systems and methods for path length selected diffuse correlation spectroscopy (PLS-DCS) are disclosed. The systems and methods are suitable for measuring dynamics of a target medium. The systems and methods can utilize light sources having a coherence length that is shorter than a path length distribution of the target medium and can utilize a reference optical path to interferometrically detect PLS-DCS signals. The coherence length and reference path length can be selected to provide sensitivity to portions of the target medium that correspond to a desired path length distribution.

We claim: 
     
         1 . A path length selected diffuse correlation spectrometry (PLS-DCS) system comprising:
 a reference optical path;   a PLS-DCS source, the PLS-DCS source configured to emit a first light having a coherence length of between 0.01 mm and 3000 mm, the PLS-DCS source configured to transmit a first portion of the first light into a target medium and a second portion of the first light along the reference optical path;   a PLS-DCS detector, the PLS-DCS detector configured to receive at least part of the first portion of the first light from the target medium and at least part of the second portion of first light from the reference optical path, the PLS-DCS detector configured to generate a PLS-DCS detector signal in response to receiving the first portion of light and the second portion of light, the PLS-DCS detector configured for interferometric detection;   a memory storing one or more equations relating correlation to dynamics of scattering particles within the target medium; and   a processor coupled to the PLS-DCS detector and the memory, the processor configured to determine a dynamics of the target medium using the PLS-DCS detector signal and the one or more equations.   
     
     
         2 . The system of  claim 1 , wherein the PLS-DCS source is a diode laser, a solid-state laser, a fiber laser, a vertical cavity surface-emitting laser (VCSEL), a Fabry-Perot laser, a ridge laser, a ridge waveguide laser, a tapered laser, a master oscillator power amplifier (MOPA) laser, or a combination thereof. 
     
     
         3 . The system of  claim 1  or  2 , wherein the PLS-DCS source is a diode laser, a solid-state laser, a fiber laser, of a combination thereof. 
     
     
         4 . The system of any of the preceding claims, wherein the PLS-DCS source is configured to emit the light at a wavelength of between 400 nm and 1500 nm. 
     
     
         5 . The system of any of the preceding claims, wherein the PLS-DCS source is configured to emit the light at an average power of between 10 μW and 10 W. 
     
     
         6 . The system of any of the preceding claims, the system further comprising a second light source. 
     
     
         7 . The system of any of the preceding claims, the system further comprising a second detector. 
     
     
         8 . The system of any of the preceding claims, wherein the PLS-DCS detector is selected from the group consisting of a single-photon avalanche photodiode detector, a photomultiplier tube, a Si, Ge, InGaAs, PbS, PbSe or HgCdTe photodiode or PIN photodiode, phototransistors, MSM photodetectors, CCD and CMOS detector arrays, silicon photomultipliers, multi-pixel-photon-counters, and combinations thereof. 
     
     
         9 . The system of any of the preceding claims, wherein the PLS-DCS detector signal is an analog signal, a digital signal, a photon-counting signal, or a combination thereof. 
     
     
         10 . The system of any of the preceding claims, wherein the reference optical path is a variable path length optical path. 
     
     
         11 . The system of any of  claims 1  to  10 , wherein the reference optical path is a fixed path length optical path. 
     
     
         12 . The system of any of the preceding claims, the system further comprising one or more waveguides configured to couple the PLS-DCS source to the target medium or configured to couple the target medium to the PLS-DCS detector. 
     
     
         13 . The system of any of the preceding claims, the system further comprising a signal processor configured to process correlation aspects of the PLS-DCS detector signal. 
     
     
         14 . The system of any of the preceding claims, wherein the system is contained in one or more handheld units. 
     
     
         15 . A method for making a path length selected diffuse correlation spectroscopy (PLS-DCS) measurement of scattering particle dynamics within a target medium, the method comprising:
 a) coupling a PLS-DCS source and a PLS-DCS detector to the target medium, the PLS-DCS source configured to emit a first light having a first coherence length of less than a path length distribution of the target medium;   b) selecting the first coherence length of the first light and/or a first path length of a first reference optical path to acquire a PLS-DCS measurement for a desired path length distribution of the target medium;   c) transmitting a first portion the first light from the PLS-DCS source into the target medium and a second portion of the first light along the first reference optical path;   d) combining at least a portion of the first portion of the first light after passing through the target medium and the second portion of the first light after passing along the first path length of the first reference optical path, thereby providing a combined optical signal;   e) receiving the combined optical signal at the PLS-DCS detector, thereby generating a PLS-DCS detector signal including path length information and correlation information for the combined optical signal;   f) determining, using a processor, the path length information, the correlation information, and one or more equations relating path length and correlation to dynamics, a dynamics of the target medium; and   g) generating a report including the dynamics of the target medium.   
     
     
         16 . The method of  claim 15 , wherein step b) includes selecting the coherence length. 
     
     
         17 . The method of  claim 15  or  16 , wherein step b) include selecting the path length. 
     
     
         18 . The method of any of  claims 15  to  17 , wherein the PLS-DCS detector signal thereby generated by the receiving of step e) is an analog signal, a digital signal, or a combination thereof. 
     
     
         19 . The method of  claim 18 , wherein the PLS-DCS detector signal thereby generated by the receiving of step c) is the analog signal. 
     
     
         20 . The method of  claim 18 , wherein the PLS-DCS detector signal thereby generated by the receiving of step c) is the digital signal. 
     
     
         21 . The method of  claim 15 ,  18 ,  19 , or  20 , wherein the determining of step d) includes determining at two or more different desired path length distributions, thereby providing depth-dependent information about the dynamics of the target medium. 
     
     
         22 . The method of  claim 15 ,  18 ,  19 , or  20 , wherein the PLS-DCS detector signal thereby generated by the receiving of step e) includes wavelength information, and the determining of step f) uses the wavelength information. 
     
     
         23 . The method of  claim 22 , wherein the wavelength information is used to enhance depth discrimination. 
     
     
         24 . The method of any of  claims 15  to  23 , wherein steps a), b), and c), are repeated with a different distance between the PLS-DCS source and the PLS-DCS detector. 
     
     
         25 . The method of  claim 24 , wherein the determining of step f) uses the different distance. 
     
     
         26 . The method of  claim 25 , wherein the determining of step f) compensates for differences in the path length information due to the different distance. 
     
     
         27 . The method of any of  claims 15  to  26 , wherein the first light has a wavelength of between 400 nm and 1500 nm. 
     
     
         28 . The method of any of  claims 15  to  27 , wherein the determining of step f) is achieved using a path length dependent autocorrelation function. 
     
     
         29 . The method of any of  claims 15  to  28 , wherein the determining of step f) includes fitting data. 
     
     
         30 . The method of  claim 29 , wherein the fitting data is achieved using a correlation decay rate versus reference path length. 
     
     
         31 . The method of any of  claims 15  to  30 , the method further comprising:
 a1) coupling a second PLS-DCS source and optionally a second PLS-DCS detector to the target medium, the second PLS-DCS source configured to emit a second light having a second coherence length of less than the path length distribution of the target medium; 
 b1) selecting the second coherence length of the second light and/or a second path length of a second reference optical path to acquire a PLS-DCS measurement for a second desired path length distribution of the target medium 
 c1) transmitting a third portion of the second light from the second PLS-DCS source into the target medium and a fourth portion of the second light along the second reference optical path; 
 d1) combining at least a portion of the third portion of the second light after passing through the target medium and the fourth portion of the second light after passing long the second path length of the second reference optical path, thereby providing a second combined optical signal; 
 e1) receiving the second combined optical signal at the PLS-DCS detector or the second PLS-DCS detector, thereby generating a second PLS-DCS detector signal including second path length information and second correlation information for the second combined optical signal, 
 the determining of step f) using the second timing information and the second correlation information. 
 
     
     
         32 . The method of  claim 31 , wherein the first light and the second light have different wavelengths. 
     
     
         33 . The method of  claim 32 , wherein the determining of step f) includes determining one or more properties of at least two distinct species of the target medium. 
     
     
         34 . The method of  claim 33 , wherein the one or more properties of the at least two distinct species of the target medium include a concentration of the at least two distinct species. 
     
     
         35 . The method of  claim 33 , wherein the at least two distinct species include oxyhemoglobin and deoxyhemoglobin. 
     
     
         36 . The method of any of  claims 15  to  35 , wherein the dynamics of the target medium include a fluid flow within the target medium. 
     
     
         37 . The method of  claim 36 , wherein the target medium is tissue and the fluid flow within the target medium is a blood flow within the tissue. 
     
     
         38 . A method of making a path length selected diffuse correlation spectroscopy (PLS-DCS) measurement of a target medium, the method comprising:
 a) coupling a PLS-DCS source and a PLS-DCS detector to a surface of the target medium;   b) transmitting a first portion of a first light from the PLS-DCS source into the target medium and a second portion of the first light along a reference optical path, the first light having a first coherence length of less than a path length distribution of the target medium;   c) interferometically detecting, using the PLS-DCS detector, at least a portion of the first portion of the first light after passing through the medium and the second portion of the first light after passing along a first path length of the reference optical path, thereby generating a first interferometric signal;   d) repeating steps b) and c), substituting a second coherence length for the first coherence length and a second path length for the first path length, thereby generating a second interferometric signal in place of the first interferometric signal, wherein the second coherence length is different than the first coherence length or the second path length is different than the first path length;   e) determining a first measured path length distribution based on the first coherence length and the first path length and a second measured path length distribution based on the second coherence length and the second path length;   f) determining, using a longer distribution between the first measured path length distribution and the second measured path length distribution, an inner dynamics of an inner portion of the target medium relative to the surface, or, using a shorter distribution between the first measured path length distribution and the second measured path length distribution, a superficial dynamics of a superficial layer of the target medium relative to the surface; and   g) generating a report including the inner dynamics or the superficial dynamics.   
     
     
         39 . The method of  claim 38 , wherein the detecting of step c) thereby generates an analog signal, a digital signal, or a combination thereof. 
     
     
         40 . The method of  claim 39 , wherein the detecting of step c) thereby generates the analog signal. 
     
     
         41 . The method of  claim 39 , wherein the detecting of step c) thereby generates the digital signal. 
     
     
         42 . The method of any of  claims 38  to  41 , wherein the first interferometric signal or the second interferometric signal includes wavelength information, and the determining of step f) uses the wavelength information. 
     
     
         43 . The method of  claim 42 , wherein the wavelength information is used to enhance depth discrimination. 
     
     
         44 . The method of any of  claims 38  to  43 , wherein steps a), b), c), and d) are repeated with a different distance between the PLS-DCS source and the PLS-DCS detector. 
     
     
         45 . The method of  claim 44 , wherein the determining of step e) uses the different distance. 
     
     
         46 . The method of any of  claims 38  to  45 , wherein the first light has a wavelength of between 400 nm and 1500 nm. 
     
     
         47 . The method of any of  claims 38  to  46 , wherein the determining of step f) is achieved using a path length dependent autocorrelation function. 
     
     
         48 . The method of any of  claims 38  to  47 , wherein the determining of step f) includes fitting data. 
     
     
         49 . The method of  claim 48 , wherein the fitting data is achieved using a correlation decay rate versus reference path length. 
     
     
         50 . The method of any of  claims 38  to  49 , the method further comprising:
 a1) coupling a second PLS-DCS source and optionally a second PLS-DCS detector to the surface of the target medium; 
 b1) transmitting a third portion of a second light from the second PLS-DCS source into the target medium and a fourth portion of the second light along a second reference optical path, the second light having a third coherence length of less than the path length distribution of the target medium; 
 c1) interferometrically detecting, using the PLS-DCS detector of the second PLS-DCS detector, at least a third portion of the third portion of the second light after passing through the medium and the fourth portion of the second light after passing along a third path length of the second reference optical path, thereby generating a third interferometric signal; 
 d1) repeating steps b1) and c1), substituting a fourth coherence length for the third coherence length and a fourth path length for the third path length, thereby generating a fourth interferometric signal in place of the second interferometric signal, wherein the fourth coherence length is different than the third coherence length or the fourth path length is different than the third path length; 
 e1) determining a third measured path length distribution based on the third coherence length and the third path length and a fourth measured path length distribution based on the fourth coherence length and the fourth path length; and 
 f1) determining, using a second longer distribution between the third measured path length distribution and the fourth measured path length distribution, the inner dynamics of the inner portion of the target medium relative to the surface, or, using a second shorter distribution between the third measured path length distribution and the fourth measured path length distribution, the superficial dynamics of the superficial layer of the target medium relative to the surface. 
 
     
     
         51 . The method of  claim 50 , wherein the first light and the second light have different wavelengths. 
     
     
         52 . The method of  claim 51 , wherein the determining of steps f) and f1) includes determining one or more properties of at least two distinct species of the target medium. 
     
     
         53 . The method of  claim 52 , wherein the one or more properties of the at least two distinct species of the target medium include a concentration of the at least two distinct species. 
     
     
         54 . The method of  claim 53 , wherein the at least two distinct species include oxyhemoglobin and deoxyhemoglobin. 
     
     
         55 . The method of any of  claims 38  to  54 , wherein the inner dynamics and/or the superficial dynamics of the target medium include a fluid flow within the target medium. 
     
     
         56 . The method of  claim 55 , wherein the target medium is tissue and the fluid flow within the target medium is a blood flow within the tissue.