DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Pending
Claims 1-27 are currently under examination.
Specification
The abstract of the disclosure is objected to because the phrase “determine, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function; estimate a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions” lacks consistency for the manner in which “normalized intensity auto-correlation function” and “intensity auto-correlation functions” are referred. It appears that the phrase “the plurality of intensity auto-correlation functions” is intended to correspond to “a normalized intensity auto-correlation function”, however, the omission of the word “normalized” creates confusion as to the intended interpretation.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
Equation 4 (Par. 75 of applicant’s spec.) is referred to as “intensity auto correlation function” (Par. 10 of applicant’s spec.), while also being referred to as “normalized intensity auto-correlation function” (Par. 75 of applicant’s spec.).
The applicant recites “determine, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function; estimate a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions” (Par. 6 of applicant’s spec.), which lacks consistency for the manner in which “normalized intensity auto-correlation function” and “intensity auto-correlation functions” are referred to. It appears that the phrase “the plurality of intensity auto-correlation functions” is intended to correspond to “a normalized intensity auto-correlation function”, however, the omission of the word “normalized” creates confusion as to the intended interpretation. (Examiner's Note: This lack of consistency persists throughout the entirety of the applicant’s specification (For example, Par. 10, 11, 12, 16…etc.)).
Appropriate correction is required.
Drawings
The drawings are objected to because Fig. 9 and 10 are blurry. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 6-7, 15-16, and 24-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 6, 15, and 24 recite the limitation “g1(ρ, τ, ω=0) is a normalized electric field auto-correlation function”, where the applicant’s specification lacks sufficient detail in regards to the structure of the function g1(ρ, τ, ω=0). The applicant’s specification does an equation with g1(τ) (Par. 79 of applicant’s spec.). However, this does not provide further detail as to the structure of the above function “g1(ρ, τ, ω=0)” for the equation of the claim. What are the terms present within the function? What are the inputs into the function? How is the output of the function determined? As such, the claim is rejected.
Claims 7, 16, and 25 recite the limitation “g1dc(τ) and g1ac(τ) are normalized electric field auto-correlation functions”, where the applicant’s specification lacks sufficient detail in regards to the structure of the functions “g1dc(τ) and g1ac(τ)”. The applicant’s specification does recite an equation with g1(τ) (Par. 79 of applicant’s spec.). The applicant further recites a derivation from Par. 92-96 of the specification. However, this merely recites the derivation of the equation of the claim rather than the above functions. What are the terms present within the functions? What are the inputs into the functions? How are the outputs of the functions determined? As such the claim is rejected.
Claims 6, 15, and 24 recite the limitation “β is a speckle averaging factor”, where the applicant’s specification lacks sufficient detail in regards to the manner in which the speckle averaging factor is determined. The applicant’s specification merely states “where β is an instrumentation factor that depends on speckle averaging” (Par. 86 of applicant’s spec.), which merely further recites that the factor depends on speckle averaging rather than providing how the factor itself is determined. How is the speckle averaging factor determined? Is the factor a constant? Does the user input the averaging factor? As such, the claim is rejected.
Claims 7, 16, and 25 recite the limitation “β is a speckle averaging factor”, where the applicant’s specification lacks sufficient detail in regards to the manner in which the speckle averaging factor is determined. The applicant’s specification merely states “where β is an instrumentation factor that depends on speckle averaging” (Par. 86 of applicant’s spec.), which merely further recites that the factor depends on speckle averaging rather than providing how the factor itself is determined. How is the speckle averaging factor determined? Is the factor a constant? Does the user input the averaging factor? As such, the claim is rejected.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-27 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitations “detect, for each of the plurality of different modulation frequencies, photon counts over a predetermined period of time; determine, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function”, which fails to effectively define the metes and bounds of the claim as it is unclear as to the relationship between “determine, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function” and “photon counts”. Is there a relationship between the photon counts and normalized intensity auto-correlation function? Is the “determine” step based on the photon counts from the detect step? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, the determine step will be interpreted as being based on the photon counts from the detecting step.
Claim 1 recites the limitation “the plurality of intensity auto-correlation functions” in lines 11-12. There is insufficient antecedent basis for this limitation in the claim. For examination purposes, this will be interpreted as -the plurality of normalized intensity auto-correlation functions-.
Claim 10 recites the limitation “the plurality of intensity auto-correlation functions” in lines 8-9. There is insufficient antecedent basis for this limitation in the claim. For examination purposes, this will be interpreted as -the plurality of normalized intensity auto-correlation functions-.
Claim 19 recites the limitation “the plurality of intensity auto-correlation functions” in lines 10-11. There is insufficient antecedent basis for this limitation in the claim. For examination purposes, this will be interpreted as -the plurality of normalized intensity auto-correlation functions-.
Claims 4, 13, and 22 recite the limitation “wherein the plurality of different modulation frequencies comprises at least one frequency in a range of 50 megahertz (MHz) and 600 MHz”, which fails to effectively define the metes and bounds of the claim as it is unclear as to the bounds of the range. For example, does the “range” solely include two values, where on is “50 megahertz (MHz)” and the other is “600 MHz”. Was the intention to claim a range from “50 megahertz (MHz)” to “600 MHz”, where 50 and 600 define the lower and upper bounds of the range? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, the range will be interpreted as -50 megahertz (MHz) to 600 MHz- (Par. 104 of applicant’s spec.).
Claims 9, 18, and 27 recite the limitation “wherein the plurality of properties comprises one or more of: oxy-hemoglobin; deoxy-hemoglobin; tissue oxygen saturation: or tissue metabolism rate of oxygen” which fails to effectively define the metes and bounds of the claim as of the claim as it is unclear what the value associated with “oxy-hemoglobin; deoxy-hemoglobin” is considered to be. For example, “tissue oxygen saturation: or tissue metabolism rate of oxygen” each recite clear values. However, there is no specific value associated with the terms “oxy-hemoglobin; deoxy-hemoglobin”. Does this refer to simply the presence of “oxy-hemoglobin; deoxy-hemoglobin”? Is this a concentration? What value of these terms is being claimed? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, “oxy-hemoglobin; deoxy-hemoglobin” will be interpreted as -oxy-hemoglobin concentration; deoxy-hemoglobin concentration- (Par. 42 of applicant’s spec.).
Claims 5, 14, and 23 recite the limitation “wherein the intensity auto-correlation function is determined based on an equation expressed as”, where it is unclear as to what “the intensity auto-correlation function” refers to. For example, claims 1, 10, and 19, which claims 5, 14, and 23 are dependent on, respectively, recites both “the plurality of intensity auto-correlation functions” and “a normalized intensity auto-correlation function”. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as -the normalized intensity auto-correlation function- (Par. 75 of applicant’s spec.).
Claims 6, 15, and 24 recites the limitations “the normalized intensity auto-correlation function is modeled based on an equation expressed as” and “estimate at least a subset of the plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions based on the modeling of the normalized intensity auto-correlation function”, which fails to effectively define the metes and bounds of the claim as it is unclear as to what “the intensity auto-correlation function” refers to. For example, claims 5, 14, and 23, which claims 6, 15, and 24 are dependent on, respectively, recites “the intensity auto-correlation function”, while claims 1, 10, and 19, which claims 5, 14, and 23 are dependent on, respectively, recites both “the plurality of intensity auto-correlation functions” and “a normalized intensity auto-correlation function”. It appears that the phrase “the plurality of intensity auto-correlation functions” is intended to correspond to “a normalized intensity auto-correlation function”, however, the removal of the word “normalized” creates confusion as to the intended interpretation. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as -estimate at least a subset of the plurality of properties of the tissue sample using the plurality of normalized intensity auto-correlation functions based on the modeling of the normalized intensity auto-correlation function-.
Claims 7, 16, and 25 recite the limitations “wherein the normalized intensity auto-correlation function is modeled based on an equation expressed as” and “estimate at least a subset of the plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions based on the modeling of the normalized intensity auto-correlation function”, which fails to effectively define the metes and bounds of the claim as it is unclear as to what “the intensity auto-correlation function” refers to. For example, claims 5, 14, and 23, which claims 7, 16, and 25 are dependent on, respectively, recites “the intensity auto-correlation function”, while claims 1, 10, and 19, which claims 5, 14, and 23 are dependent on, respectively, recites both “the plurality of intensity auto-correlation functions” and “a normalized intensity auto-correlation function”. It appears that the phrase “the plurality of intensity auto-correlation functions” is intended to correspond to “a normalized intensity auto-correlation function”, however, the removal of the word “normalized” creates confusion as to the intended interpretation. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as -estimate at least a subset of the plurality of properties of the tissue sample using the plurality of normalized intensity auto-correlation functions based on the modeling of the normalized intensity auto-correlation function-.
Claims 6, 15, and 24 recite the limitation “g1(ρ, τ, ω=0) is a normalized electric field auto-correlation function”, which fails to effectively define the metes and bounds of the claim as it is unclear as to the structure of the function g1(ρ, τ, ω=0). What are the terms present within the function? What are the inputs into the function? How is the output of the function determined? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as the electric field function in Par. 79 of the applicant’s specification.
Claims 6, 15, and 24 recite the limitation “β is a speckle averaging factor”, which fails to effectively define the metes and bounds of the claim as it is unclear as to where the “β is a speckle averaging factor” originates for the equation of the claim. How is the speckle averaging factor determined? Is the factor a constant? Does the user input the averaging factor? The applicant’s specification merely states “where β is an instrumentation factor that depends on speckle averaging” (Par. 86 of applicant’s spec.), which merely further recites that the factor depends on speckle averaging. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as any type of constant related to the instrumentation.
Claims 6, 15, and 24 recite the limitation “m is modulation depth”, which fails to effectively define the metes and bounds of the claim as it is unclear as to where the “m is modulation depth” originates for the equation of the claim. How is the modulation depth determined? Is the modulation depth a constant? Does the user input the modulation depth? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as a constant that is input where “m is the modulation depth of the source (0≤m≤1)” (Par. 83 of applicant’s spec.).
Claims 7, 16, and 25 recite the limitation “β is a speckle averaging factor”, which fails to effectively define the metes and bounds of the claim as it is unclear as to where the “β is a speckle averaging factor” originates for the equation of the claim. How is the speckle averaging factor determined? Is the factor a constant? Does the user input the averaging factor? The applicant’s specification merely states “where β is an instrumentation factor that depends on speckle averaging” (Par. 86 of applicant’s spec.), which merely further recites that the factor depends on speckle averaging. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as any type of constant related to the instrumentation.
Claims 7, 16, and 25 recite the limitation “m is modulation depth”, which fails to effectively define the metes and bounds of the claim as it is unclear as to where the “m is modulation depth” originates for the equation of the claim. How is the modulation depth determined? Is the modulation depth a constant? Does the user input the modulation depth? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as a constant that is input where “m is the modulation depth of the source (0≤m≤1)” (Par. 83 of applicant’s spec.).
Claims 7, 16, and 25 recite the limitation “g1dc(τ) and g1ac(τ) are normalized electric field auto-correlation functions”, where it is unclear as to the structure of the functions “g1dc(τ) and g1ac(τ)”. What are the terms present within the functions? What are the inputs into the functions? How are the outputs of the functions determined? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, these functions will be each be interpreted as the electric field function in Par. 79 of the applicant’s specification.
Claims 2-9, 11-18, and 20-27 are dependent on claims 1, 10, and 19, respectively, and as such are also rejected.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The claims are generally directed towards a system for frequency domain diffuse correlation spectroscopy. The system comprises emitting a light source towards a tissue sample, detecting photon counts for the emitted light, determining a normalized intensity auto-correlation function, estimating tissue properties using the normalized intensity auto-correlation functions, and outputting at least one of the plurality of properties.
Claim(s) 1-4, 8-13, 17-22, and 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Franceschini (US Pub. No. 20190261869) hereinafter Maria, and further in view of Sutin (US Pub. No. 20180070830) hereinafter Sutin and Yodh (US Pub. No. 20160353997) hereinafter Yodh.
Regarding claim 1, Maria discloses A system for frequency domain diffuse correlation spectroscopy (Abstract)(Par. 87, “the methods described herein can combine DCS with CW and time-domain or frequency-domain NIRS.”), comprising:
an intensity modulated coherent light source (Par. 33, “The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a light source that is capable of emitting optical signals having the properties described elsewhere in the present disclosure. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a single-mode laser, a multi-mode laser, combinations thereof, and the like. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be 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, or other type of laser.”) (Par. 44, “In certain aspects, the one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n, the second DCS light source 12, 112-2, the third, fourth, fifth, up to nth DCS light source 12-n, 112-n, or any additional light sources can include one or more amplifiers to amplify the intensity of the emitted light.”);
a photon counting detector (Par. 51, “one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can be an avalanche photodiode detector, such as a single-photon avalanche photodiode detector,”)(Par. 52, “The one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can provide a detector signal that can be analog, digital, photon-counting, or any combination thereof.”);
at least one hardware processor that is programmed to (Par. 63, “The computer 16 can include various components known to a person having ordinary skill in the art, such as a processor and/or a CPU 24, memory 26 of various types, interfaces, and the like. The computer 16 can be a single computing device or can be a plurality of computing devices operating in a coordinated fashion.”)(Par. 67, “The processor and/or CPU 24 can be configured to read and perform computer-executable instructions stored in the memory 26. The computer-executable instructions can include all or portions of the methods described herein.”):
cause the light source to emit light toward a tissue sample (Par. 33-34 (transmit light into target medium)) (Par. 80 (light transmitted into a target medium));
determine, a normalized intensity auto-correlation function (Par. 90, “In certain aspects, the correlation described herein can be normalized or unnormalized.”) (Par. 111, “We also developed a correlator board that provides the multiplexing signals and performs autocorrelation functions synchronized to each wavelength.”) (Par. 43, “The correlation functions can be autocorrelation functions calculated from individual detectors, autocorrelation functions calculated from multiple detectors, cross-correlation functions calculated between different detectors, or any combination thereof.”) (Par. 99, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999)”);
estimate a plurality of properties of the tissue sample using the intensity auto-correlation (Par. 80, “The determining of process block 110 can use the processor, the decay of the autocorrelation function over distance, and one or more equations relating the decay of the autocorrelation function over distance to optical properties and dynamics of the target medium.”) (Par. 43, “In this aspect, the multi-distance DCS intensity measurements provide intensity decay over distance, which results in a slope that is proportional to the product μ.sub.aμ.sub.s′. In certain aspects, the measurements of the decay of the autocorrelation function at three or more wavelengths can provide independent measurements to uniquely determine all parameters of interest for measuring fluid flow. These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability with respect the prior art.”) (Par. 86, “Use of multiple source-detector distances can provide better discrimination between various different depths of measurement, such as between cerebral and extra-cerebral measurements, and can provide increased accuracy for the estimation of the properties of the medium and corresponding flow determinations.”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”), and
output at least one of the plurality of properties (Par. 83, “generating a report of process block 112 can include generating a printed report, displaying results on a screen, transmitting results to a computer database, or another means of reporting the mathematically modeled fluid flow”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”).
Maria fails to explicitly disclose cause the light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample.
Maria does disclose cause the light source to emit light toward a tissue sample (Par. 33-34 (transmit light into target medium)) (Par. 80 (light transmitted into a target medium from one or more sources)).
Maria does teach the combination of different spectroscopy methods (Par. 87, “In certain aspect, the methods described herein can combine DCS with CW and time-domain or frequency-domain NIRS. Again, one of the surprising advantages of the present disclosure is that the need for NIRS to determine properties of the target medium is no longer required. However, the systems and methods described herein can still be used with NIRS without deviating from the present disclosure.”) and additional measurements (Par. 86, “the methods described herein can utilize measurement at two, three, four, five, six, or more, up ton source-detector distances”).
However, Sutin teaches light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria with that of Sutin to include cause the light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose detect, for each of the plurality of different modulation frequencies, photon counts over a predetermined period of time.
However, Maria does disclose detect, photon counts over a predetermined period of time (Par. 80, “At process block 106, the method 100 includes receiving at least a portion of the first and second light at the one or more DCS detectors, thereby generating a DCS detector signal. The DCS detector signal includes photon arrival time information, wavelength information, and source-detector distance information”)(Par. 92, “Calculations, separation, and/or discrimination in the methods described herein can be performed in real-time, near real-time, post-processing, or a combination thereof. These operations can be performed continuously, quasi-continuously, and/or continually, or periodically, and/or intermittently or in batches, or any combination thereof.”) (Par. 52, “The one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can provide a detector signal that can be analog, digital, photon-counting, or any combination thereof.”) (Par. 79, “This disclosure provides a method 100 for using the systems 10 described above, although the method 100 can optionally be used with other systems not described herein.”).
Maria further discloses photon counting detectors (Par. 51, “one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can be an avalanche photodiode detector, such as a single-photon avalanche photodiode detector”).
Sutin further teaches for each of the plurality of different modulation frequencies (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria and Sutin with that of Sutin to include detect, for each of the plurality of different modulation frequencies of Sutin, photon counts over a predetermined period of time through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose determine, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function. (Examiner's Note: Interpreted as the determining being based on the photon count as indicated in the 112b rejection above).
However, Maria does disclose determine, a normalized intensity auto-correlation function (Par. 90, “In certain aspects, the correlation described herein can be normalized or unnormalized.”) (Par. 111, “We also developed a correlator board that provides the multiplexing signals and performs autocorrelation functions synchronized to each wavelength.”) (Par. 43, “The correlation functions can be autocorrelation functions calculated from individual detectors, autocorrelation functions calculated from multiple detectors, cross-correlation functions calculated between different detectors, or any combination thereof.”) (Par. 99, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999)”).
Yodh teaches determine, for each of the plurality, a normalized intensity auto-correlation function (Par. 120, “An exemplary DCS instrument used in this study is shown in FIG. 3—left. The portable device consists of 2 long coherence length near infrared lasers (785 nm, Crystalaser) and 8 photon counting avalanche photodiodes (APD, Perkin Elmer), connected to flexible single mode fiber optics (Fiberoptic Systems Inc.). A built-in correlator (Correlator.com) reads the photon counts from the APDs and computes the intensity correlation function”) (Par. 144, “A device may also include an element configured to compute intensity correlation functions from photon counts, the device being in electronic communication, optical communication, or both with a illumination detector probe.”) (Par. 163, “These temporal fluctuations (FIG. 8B) are quantified by computing the normalized intensity temporal auto-correlation function at multiple delay-times”) (Par. 271, “The disclosed systems may further comprise a device configured to compute intensity correlation functions from photon counts”).
Sutin further teaches for each of the plurality of modulation frequencies (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Maria, Sutin, and Yodh are considered to be analogous art to the claimed invention as they are involved with diffuse correlation spectroscopy.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria and Sutin with that of Sutin and Yodh to include determine, for each of the plurality of modulation frequencies of Sutin, a normalized intensity auto-correlation function through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) (Yodh (Par. 120)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose estimate a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions.
However, Maria does disclose estimate a plurality of properties of the tissue sample using the intensity auto-correlation function (Par. 80, “The determining of process block 110 can use the processor, the decay of the autocorrelation function over distance, and one or more equations relating the decay of the autocorrelation function over distance to optical properties and dynamics of the target medium.”) (Par. 43, “In this aspect, the multi-distance DCS intensity measurements provide intensity decay over distance, which results in a slope that is proportional to the product μ.sub.aμ.sub.s′. In certain aspects, the measurements of the decay of the autocorrelation function at three or more wavelengths can provide independent measurements to uniquely determine all parameters of interest for measuring fluid flow. These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability with respect the prior art.”) (Par. 86, “Use of multiple source-detector distances can provide better discrimination between various different depths of measurement, such as between cerebral and extra-cerebral measurements, and can provide increased accuracy for the estimation of the properties of the medium and corresponding flow determinations.”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”).
Yodh further teaches estimate a plurality of properties using the plurality of intensity auto-correlation functions (Par. 120, “… A built-in correlator (Correlator.com) reads the photon counts from the APDs and computes the intensity correlation function”) (Par. 144, “A device may also include an element configured to compute intensity correlation functions from photon counts, the device being in electronic communication, optical communication, or both with a illumination detector probe.”) (Par. 163, “DCS detects tissue blood flow using speckle correlation techniques. It measures the temporal intensity fluctuations of coherent NIR light that has scattered from moving particles (red blood cells) in tissue (FIG. 8A)…” “…transport of temporal field fluctuations through turbid media is modelled by the so-called correlation diffusion equation, and the decay of the detected autocorrelation function determines a tissue blood flow index (FIG. 8C).”) (Par. 271, “The disclosed systems may further comprise a device configured to compute intensity correlation functions from photon counts”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria, Sutin, and Yodh with that of Yodh to include estimate a plurality of properties of the tissue sample using the plurality of intensity auto-correlation function through the combination of references as the use of additional measurements is known (Maria (Par. 86)) (Yodh (Par. 120)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Regarding claim 10, Maria discloses A method for frequency domain diffuse correlation spectroscopy (Abstract)(Par. 87, “the methods described herein can combine DCS with CW and time-domain or frequency-domain NIRS.”), comprising:
causing an intensity modulated coherent light source to emit light toward a tissue sample (Par. 80 (light transmitted into a target medium)) (Par. 33, “The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a light source that is capable of emitting optical signals having the properties described elsewhere in the present disclosure. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a single-mode laser, a multi-mode laser, combinations thereof, and the like. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be 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, or other type of laser.”) (Par. 44, “In certain aspects, the one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n, the second DCS light source 12, 112-2, the third, fourth, fifth, up to nth DCS light source 12-n, 112-n, or any additional light sources can include one or more amplifiers to amplify the intensity of the emitted light.”);
determining, a normalized intensity auto-correlation function (Par. 90, “In certain aspects, the correlation described herein can be normalized or unnormalized.”) (Par. 111, “We also developed a correlator board that provides the multiplexing signals and performs autocorrelation functions synchronized to each wavelength.”) (Par. 43, “The correlation functions can be autocorrelation functions calculated from individual detectors, autocorrelation functions calculated from multiple detectors, cross-correlation functions calculated between different detectors, or any combination thereof.”) (Par. 99, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999)”);
estimating a plurality of properties of the tissue sample using the intensity auto-correlation function (Par. 80, “The determining of process block 110 can use the processor, the decay of the autocorrelation function over distance, and one or more equations relating the decay of the autocorrelation function over distance to optical properties and dynamics of the target medium.”) (Par. 43, “In this aspect, the multi-distance DCS intensity measurements provide intensity decay over distance, which results in a slope that is proportional to the product μ.sub.aμ.sub.s′. In certain aspects, the measurements of the decay of the autocorrelation function at three or more wavelengths can provide independent measurements to uniquely determine all parameters of interest for measuring fluid flow. These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability with respect the prior art.”) (Par. 86, “Use of multiple source-detector distances can provide better discrimination between various different depths of measurement, such as between cerebral and extra-cerebral measurements, and can provide increased accuracy for the estimation of the properties of the medium and corresponding flow determinations.”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”); and
outputting at least one of the plurality of properties (Par. 83, “generating a report of process block 112 can include generating a printed report, displaying results on a screen, transmitting results to a computer database, or another means of reporting the mathematically modeled fluid flow”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”).
Maria fails to explicitly disclose causing an intensity modulated coherent light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample.
Maria does disclose causing an intensity modulated coherent light source to emit light to emit light toward a tissue sample (Par. 33, “The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a light source that is capable of emitting optical signals having the properties described elsewhere in the present disclosure. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a single-mode laser, a multi-mode laser, combinations thereof, and the like. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be 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, or other type of laser.”) (Par. 44, “In certain aspects, the one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n, the second DCS light source 12, 112-2, the third, fourth, fifth, up to nth DCS light source 12-n, 112-n, or any additional light sources can include one or more amplifiers to amplify the intensity of the emitted light.”) (Par. 80 (light transmitted into a target medium from one or more sources)).
Maria does teach the combination of different spectroscopy methods (Par. 87, “In certain aspect, the methods described herein can combine DCS with CW and time-domain or frequency-domain NIRS. Again, one of the surprising advantages of the present disclosure is that the need for NIRS to determine properties of the target medium is no longer required. However, the systems and methods described herein can still be used with NIRS without deviating from the present disclosure.”) and additional measurements (Par. 86, “the methods described herein can utilize measurement at two, three, four, five, six, or more, up ton source-detector distances”).
However, Sutin teaches an intensity modulated coherent light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria with that of Sutin to include causing an intensity modulated coherent light source to emit light at a plurality of different intensity modulation frequencies of Sutin toward a tissue sample through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose detecting, for each of the plurality of different modulation frequencies, photon counts over a predetermined period of time using a photon counting detector.
However, Maria does disclose detecting, photon counts over a predetermined period of time (Par. 80, “At process block 106, the method 100 includes receiving at least a portion of the first and second light at the one or more DCS detectors, thereby generating a DCS detector signal. The DCS detector signal includes photon arrival time information, wavelength information, and source-detector distance information”)(Par. 92, “Calculations, separation, and/or discrimination in the methods described herein can be performed in real-time, near real-time, post-processing, or a combination thereof. These operations can be performed continuously, quasi-continuously, and/or continually, or periodically, and/or intermittently or in batches, or any combination thereof.”) (Par. 52, “The one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can provide a detector signal that can be analog, digital, photon-counting, or any combination thereof.”) (Par. 79, “This disclosure provides a method 100 for using the systems 10 described above, although the method 100 can optionally be used with other systems not described herein.”).
Maria further discloses photon counting detectors (Par. 51, “one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can be an avalanche photodiode detector, such as a single-photon avalanche photodiode detector”).
Sutin further teaches for each of the plurality of different modulation frequencies (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria and Sutin with that of Sutin to include detecting, for each of the plurality of different modulation frequencies of Sutin, photon counts over a predetermined period of time using a photon counting detector through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose determining, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function (Examiner's Note: Interpreted as the determining being based on the photon count as indicated in the 112b rejection above).
However, Maria does disclose determining, a normalized intensity auto-correlation function (Par. 90, “In certain aspects, the correlation described herein can be normalized or unnormalized.”) (Par. 43, “The correlation functions can be autocorrelation functions calculated from individual detectors, autocorrelation functions calculated from multiple detectors, cross-correlation functions calculated between different detectors, or any combination thereof.”) (Par. 99, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999)”).
Yodh teaches determining, for each of the plurality, a normalized intensity auto-correlation function (Par. 120, “An exemplary DCS instrument used in this study is shown in FIG. 3—left. The portable device consists of 2 long coherence length near infrared lasers (785 nm, Crystalaser) and 8 photon counting avalanche photodiodes (APD, Perkin Elmer), connected to flexible single mode fiber optics (Fiberoptic Systems Inc.). A built-in correlator (Correlator.com) reads the photon counts from the APDs and computes the intensity correlation function”) (Par. 144, “A device may also include an element configured to compute intensity correlation functions from photon counts, the device being in electronic communication, optical communication, or both with a illumination detector probe.”) (Par. 163, “These temporal fluctuations (FIG. 8B) are quantified by computing the normalized intensity temporal auto-correlation function at multiple delay-times”) (Par. 271, “The disclosed systems may further comprise a device configured to compute intensity correlation functions from photon counts”).
Sutin further teaches for each of the plurality of modulation frequencies (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Maria, Sutin, and Yodh are considered to be analogous art to the claimed invention as they are involved with diffuse correlation spectroscopy.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria and Sutin with that of Sutin and Yodh to include determining, for each of the plurality of modulation frequencies of Sutin, a normalized intensity auto-correlation function through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) (Yodh (Par. 120)) and it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose estimate a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions.
However, Maria does disclose estimating a plurality of properties of the tissue sample using the intensity auto-correlation function (Par. 80, “The determining of process block 110 can use the processor, the decay of the autocorrelation function over distance, and one or more equations relating the decay of the autocorrelation function over distance to optical properties and dynamics of the target medium.”) (Par. 43, “In this aspect, the multi-distance DCS intensity measurements provide intensity decay over distance, which results in a slope that is proportional to the product μ.sub.aμ.sub.s′. In certain aspects, the measurements of the decay of the autocorrelation function at three or more wavelengths can provide independent measurements to uniquely determine all parameters of interest for measuring fluid flow. These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability with respect the prior art.”) (Par. 86, “Use of multiple source-detector distances can provide better discrimination between various different depths of measurement, such as between cerebral and extra-cerebral measurements, and can provide increased accuracy for the estimation of the properties of the medium and corresponding flow determinations.”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”).
Yodh further teaches estimating a plurality of properties using the plurality of intensity auto-correlation functions (Par. 120, “… A built-in correlator (Correlator.com) reads the photon counts from the APDs and computes the intensity correlation function”) (Par. 144, “A device may also include an element configured to compute intensity correlation functions from photon counts, the device being in electronic communication, optical communication, or both with a illumination detector probe.”) (Par. 163, “DCS detects tissue blood flow using speckle correlation techniques. It measures the temporal intensity fluctuations of coherent NIR light that has scattered from moving particles (red blood cells) in tissue (FIG. 8A)…” “…transport of temporal field fluctuations through turbid media is modelled by the so-called correlation diffusion equation, and the decay of the detected autocorrelation function determines a tissue blood flow index (FIG. 8C).”) (Par. 271, “The disclosed systems may further comprise a device configured to compute intensity correlation functions from photon counts”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria, Sutin, and Yodh with that of Yodh to include estimating a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions through the combination of references as the use of additional measurements is known (Maria (Par. 86)) (Yodh (Par. 120)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Regarding claim 19, Maria discloses A non-transitory computer readable medium containing computer executable instructions that, when executed by a processor, cause the processor to perform a method for frequency domain diffuse correlation spectroscopy, the method comprising (Abstract)(Par. 87, “the methods described herein can combine DCS with CW and time-domain or frequency-domain NIRS.”) (Par. 67, “The processor and/or CPU 24 can be configured to read and perform computer-executable instructions stored in the memory 26. The computer-executable instructions can include all or portions of the methods described herein.”) (Par. 63, “The computer 16 can include various components known to a person having ordinary skill in the art, such as a processor and/or a CPU 24, memory 26 of various types, interfaces, and the like. The computer 16 can be a single computing device or can be a plurality of computing devices operating in a coordinated fashion.”):
causing an intensity modulated coherent light source to emit light toward a tissue sample (Par. 80 (light transmitted into a target medium)) (Par. 33, “The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a light source that is capable of emitting optical signals having the properties described elsewhere in the present disclosure. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a single-mode laser, a multi-mode laser, combinations thereof, and the like. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be 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, or other type of laser.”) (Par. 44, “In certain aspects, the one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n, the second DCS light source 12, 112-2, the third, fourth, fifth, up to nth DCS light source 12-n, 112-n, or any additional light sources can include one or more amplifiers to amplify the intensity of the emitted light.”);
determining, a normalized intensity auto-correlation function (Par. 90, “In certain aspects, the correlation described herein can be normalized or unnormalized.”) (Par. 111, “We also developed a correlator board that provides the multiplexing signals and performs autocorrelation functions synchronized to each wavelength.”) (Par. 43, “The correlation functions can be autocorrelation functions calculated from individual detectors, autocorrelation functions calculated from multiple detectors, cross-correlation functions calculated between different detectors, or any combination thereof.”) (Par. 99, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999)”);
estimating a plurality of properties of the tissue sample using the intensity auto-correlation function (Par. 80, “The determining of process block 110 can use the processor, the decay of the autocorrelation function over distance, and one or more equations relating the decay of the autocorrelation function over distance to optical properties and dynamics of the target medium.”) (Par. 43, “In this aspect, the multi-distance DCS intensity measurements provide intensity decay over distance, which results in a slope that is proportional to the product μ.sub.aμ.sub.s′. In certain aspects, the measurements of the decay of the autocorrelation function at three or more wavelengths can provide independent measurements to uniquely determine all parameters of interest for measuring fluid flow. These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability with respect the prior art.”) (Par. 86, “Use of multiple source-detector distances can provide better discrimination between various different depths of measurement, such as between cerebral and extra-cerebral measurements, and can provide increased accuracy for the estimation of the properties of the medium and corresponding flow determinations.”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”); and
outputting at least one of the plurality of properties (Par. 83, “generating a report of process block 112 can include generating a printed report, displaying results on a screen, transmitting results to a computer database, or another means of reporting the mathematically modeled fluid flow”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”).
Maria fails to explicitly disclose causing an intensity modulated coherent light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample.
Maria does disclose causing an intensity modulated coherent light source to emit light to emit light toward a tissue sample (Par. 33, “The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a light source that is capable of emitting optical signals having the properties described elsewhere in the present disclosure. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be a single-mode laser, a multi-mode laser, combinations thereof, and the like. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be 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, or other type of laser.”) (Par. 44, “In certain aspects, the one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n, the second DCS light source 12, 112-2, the third, fourth, fifth, up to nth DCS light source 12-n, 112-n, or any additional light sources can include one or more amplifiers to amplify the intensity of the emitted light.”) (Par. 80 (light transmitted into a target medium from one or more sources)).
Maria does teach the combination of different spectroscopy methods (Par. 87, “In certain aspect, the methods described herein can combine DCS with CW and time-domain or frequency-domain NIRS. Again, one of the surprising advantages of the present disclosure is that the need for NIRS to determine properties of the target medium is no longer required. However, the systems and methods described herein can still be used with NIRS without deviating from the present disclosure.”) and additional measurements (Par. 86, “the methods described herein can utilize measurement at two, three, four, five, six, or more, up ton source-detector distances”).
However, Sutin teaches an intensity modulated coherent light source to emit light at a plurality of different intensity modulation frequencies toward a tissue sample (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria with that of Sutin to include causing an intensity modulated coherent light source to emit light at a plurality of different intensity modulation frequencies of Sutin toward a tissue sample through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose detecting, for each of the plurality of different modulation frequencies, photon counts over a predetermined period of time using a photon counting detector.
However, Maria does disclose detecting, photon counts over a predetermined period of time (Par. 80, “At process block 106, the method 100 includes receiving at least a portion of the first and second light at the one or more DCS detectors, thereby generating a DCS detector signal. The DCS detector signal includes photon arrival time information, wavelength information, and source-detector distance information”)(Par. 92, “Calculations, separation, and/or discrimination in the methods described herein can be performed in real-time, near real-time, post-processing, or a combination thereof. These operations can be performed continuously, quasi-continuously, and/or continually, or periodically, and/or intermittently or in batches, or any combination thereof.”) (Par. 52, “The one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can provide a detector signal that can be analog, digital, photon-counting, or any combination thereof.”) (Par. 79, “This disclosure provides a method 100 for using the systems 10 described above, although the method 100 can optionally be used with other systems not described herein.”).
Maria further discloses photon counting detectors (Par. 51, “one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can be an avalanche photodiode detector, such as a single-photon avalanche photodiode detector”).
Sutin further teaches for each of the plurality of different modulation frequencies (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria and Sutin with that of Sutin to include detecting, for each of the plurality of different modulation frequencies of Sutin, photon counts over a predetermined period of time using a photon counting detector through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose determining, for each of the plurality of modulation frequencies, a normalized intensity auto-correlation function (Examiner's Note: Interpreted as the determining being based on the photon count as indicated in the 112b rejection above).
However, Maria does disclose determining, a normalized intensity auto-correlation function (Par. 90, “In certain aspects, the correlation described herein can be normalized or unnormalized.”) (Par. 43, “The correlation functions can be autocorrelation functions calculated from individual detectors, autocorrelation functions calculated from multiple detectors, cross-correlation functions calculated between different detectors, or any combination thereof.”) (Par. 99, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999)”).
Yodh teaches determining, for each of the plurality, a normalized intensity auto-correlation function (Par. 120, “An exemplary DCS instrument used in this study is shown in FIG. 3—left. The portable device consists of 2 long coherence length near infrared lasers (785 nm, Crystalaser) and 8 photon counting avalanche photodiodes (APD, Perkin Elmer), connected to flexible single mode fiber optics (Fiberoptic Systems Inc.). A built-in correlator (Correlator.com) reads the photon counts from the APDs and computes the intensity correlation function”) (Par. 144, “A device may also include an element configured to compute intensity correlation functions from photon counts, the device being in electronic communication, optical communication, or both with a illumination detector probe.”) (Par. 163, “These temporal fluctuations (FIG. 8B) are quantified by computing the normalized intensity temporal auto-correlation function at multiple delay-times”) (Par. 271, “The disclosed systems may further comprise a device configured to compute intensity correlation functions from photon counts”).
Sutin further teaches for each of the plurality of modulation frequencies (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Maria, Sutin, and Yodh are considered to be analogous art to the claimed invention as they are involved with diffuse correlation spectroscopy.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria and Sutin with that of Sutin and Yodh to include determining, for each of the plurality of modulation frequencies of Sutin, a normalized intensity auto-correlation function through the combination of references and explicitly using the different intensity modulation frequencies of Sutin as the use of additional measurements is known (Maria (Par. 86)) (Yodh (Par. 120)) and it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Modified Maria fails to explicitly disclose estimate a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions.
However, Maria does disclose estimating a plurality of properties of the tissue sample using the intensity auto-correlation function (Par. 80, “The determining of process block 110 can use the processor, the decay of the autocorrelation function over distance, and one or more equations relating the decay of the autocorrelation function over distance to optical properties and dynamics of the target medium.”) (Par. 43, “In this aspect, the multi-distance DCS intensity measurements provide intensity decay over distance, which results in a slope that is proportional to the product μ.sub.aμ.sub.s′. In certain aspects, the measurements of the decay of the autocorrelation function at three or more wavelengths can provide independent measurements to uniquely determine all parameters of interest for measuring fluid flow. These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability with respect the prior art.”) (Par. 86, “Use of multiple source-detector distances can provide better discrimination between various different depths of measurement, such as between cerebral and extra-cerebral measurements, and can provide increased accuracy for the estimation of the properties of the medium and corresponding flow determinations.”) (Par. 84, “the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”).
Yodh further teaches estimating a plurality of properties using the plurality of intensity auto-correlation functions (Par. 120, “… A built-in correlator (Correlator.com) reads the photon counts from the APDs and computes the intensity correlation function”) (Par. 144, “A device may also include an element configured to compute intensity correlation functions from photon counts, the device being in electronic communication, optical communication, or both with a illumination detector probe.”) (Par. 163, “DCS detects tissue blood flow using speckle correlation techniques. It measures the temporal intensity fluctuations of coherent NIR light that has scattered from moving particles (red blood cells) in tissue (FIG. 8A)…” “…transport of temporal field fluctuations through turbid media is modelled by the so-called correlation diffusion equation, and the decay of the detected autocorrelation function determines a tissue blood flow index (FIG. 8C).”) (Par. 271, “The disclosed systems may further comprise a device configured to compute intensity correlation functions from photon counts”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Maria, Sutin, and Yodh with that of Yodh to include estimating a plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions through the combination of references as the use of additional measurements is known (Maria (Par. 86)) (Yodh (Par. 120)) and as it would have yielded the predictable result of providing additional data points for the determination of the dynamics of the target medium.
Regarding claim 2, modified Maria further discloses wherein the intensity modulated coherent light source comprises:
a laser (Maria (Par. 33, “sources 12, 12-2, 12-3, . . . , 12-n can be a single-mode laser, a multi-mode laser, combinations thereof, and the like. The one or more DCS light sources 12, 12-2, 12-3, . . . , 12-n can be 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, or other type of laser.”)); and
a signal generator (Maria (Par. 49, “the light source control 22 can be configured to control the sequence of the source for time division multiplexing between different sources.”) (Par. 50, “In certain aspects, the light source control 22 can be a component of the computer 16. In certain aspects, the light source control 22 can be a standalone component or multiple standalone components. One light source control 22 can control all or some of the various light sources or each of the various light sources can have its own light source control 22.”)).
Regarding claims 11 and 20, modified Maria discloses the system of claim 2 above, which describes the methods of claim 11 and 20. As the claims are similar, claims 11 and 20 are rejected in the same manner as claim 2.
Regarding claim 3, modified Maria further discloses wherein the photon counting detector comprises an avalanche photodiode (Maria (Par. 51, “The one or more DCS detectors 14, 14-2, 14-3, . . . , 14-n can be an avalanche photodiode detector, such as a single-photon avalanche photodiode detector”)).
Regarding claims 12 and 21, modified Maria discloses the system of claim 3 above, which describes the methods of claim 12 and 21. As the claims are similar, claims 12 and 21 are rejected in the same manner as claim 3.
Regarding claim 4, modified Maria fails to explicitly disclose the limitations of the claim.
Sutin further teaches wherein the plurality of different modulation frequencies comprises at least one frequency in a range of 50 megahertz (MHz) and 600 MHz (Par. 61, “In aspects where the TR-DCS source 12, 112 is a swept source light source and the emitted light is modulated, the modulation described herein can be amplitude modulation and/or can be sweeping the source. The modulation can sweep the wavelength of the source.”) (Par. 60, “The TR-DCS source 12, 112 can emit light that is pulsed, sinusoidally modulated, step modulated, triangularly modulated, and/or arbitrarily modulated.”) (Par. 59, “…In certain aspects, the TR-DCS source 12, 112 can be a swept source light source.”) (Par. 65, “The TR-DCS source 12, 112 can be configured to transmit pulses of light into the target medium 20, 120 having a pulse repetition rate of up to 1 GHz, including but not limited to a frequency of between 1 kHz and 1 GHz, between 100 kHz and 500 MHz, or between 10 MHz and 400 MHz.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria, Sutin, and Yodh with that of Sutin to include wherein the plurality of different modulation frequencies comprises at least one frequency in a range of 50 megahertz (MHz) and 600 MHz for the reasoning as indicated in claim 1 above.
Regarding claim 8, modified Maria fails to explicitly disclose the limitations of the claim.
Maria does disclose a plurality of properties (Par. 84, “(Maria (Par. 84, “In certain aspects, the dynamics that are determined by the methods described herein can be fluid flow, shear flow, diffusional properties, motion, association, dis-association, aggregation, dis-aggregation, and/or rotational dynamics of the optical scattering particles within the target medium, and the like.”)).
However, Maria does teach in an embodiment wherein the plurality of properties comprises:
a tissue blood flow index F;
an absorption coefficient μa; and
a scattering coefficient μ′s (Maria (Par. 8, “generating a DCS detector signal including light intensity, autocorrelation, wavelength information, and source-detector distance information; d) determining, using (1) a processor, (2) the DCS detector signal, and (3) a global fitting method, (i) an absorption coefficient (μ.sub.a), (ii) a reduced scattering coefficient (μ.sub.s′), and (iii) a blood flow index (BFi); and e) generating a report including the absorption coefficient, the reduced scattering coefficient, or the blood flow index”)).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria, Sutin, and Yodh with that of Maria to include wherein the plurality of properties comprises: a tissue blood flow index F; an absorption coefficient μa; and a scattering coefficient μ′s through the combination of embodiments as differing dynamics are known (Maria (Par. 84)) it would have yielded the predictable result of explicitly providing differing metrics regarding the target medium (Maria (Par. 84)).
Regarding claims 17 and 26, modified Maria discloses the system of claim 8 above, which describes the methods of claim 17 and 26. As the claims are similar, claims 17 and 26 are rejected in the same manner as claim 8.
Regarding claim 9, modified Maria fails to explicitly disclose the limitations of the claim.
Maria does disclose plurality of properties (Maria (Par. 43, “These parameters can be used to estimate flow, hemoglobin concentrations and/or blood oxygenation, and result in improved accuracy, precision, and reduced variability”))
However, Maria does teach in an embodiment wherein the plurality of properties comprises one or more of:
oxy-hemoglobin (Maria (Par. 100, “decouple the contribution of static (absorption and scattering) and dynamic (flow) properties of the tissue at large separations, which enables us to simultaneously estimate BE, hemoglobin oxygenation (SO.sub.2) and oxygenated and deoxygenated hemoglobin concentrations (HbO and HbR, respectively).”));
deoxy-hemoglobin;
tissue oxygen saturation; or
tissue metabolism rate of oxygen.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria, Sutin, and Yodh with that of Maria to include wherein the plurality of properties comprises one or more of: oxy-hemoglobin; deoxy-hemoglobin; tissue oxygen saturation; or tissue metabolism rate of oxygen through the combination of embodiments as differing dynamics are known (Maria (Par. 84)) it would have yielded the predictable result of improving accuracy (Maria (Par. 43)).
Regarding claims 18 and 27, modified Maria discloses the system of claim 9 above, which describes the methods of claim 18 and 27. As the claims are similar, claims 18 and 27 are rejected in the same manner as claim 9.
Claim(s) 5, 14, and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maria in view of Sutin and Yodh as applied to claims 1, 10, and 19 above, and further in view of Hosoda (US Pub. No. 20180372544) hereinafter Hosoda.
Maria, Sutin, and Yodh teach the system of claim 1, method of claim 10, and method of claim 19 above.
Regarding claim 5, modified Maria fails to explicitly disclose the limitations of the claim.
However, Hosoda teaches wherein the intensity auto-correlation function is determined based on an equation expressed as:
(Examiner's Note: Applicant’s Equation of claim 5)
where I(t) is intensity at the photon counting detector at time t, and I(t+τ) is intensity at the photon counting detector at time t+τ (Par. 21, “Calculating the intensity autocorrelation function, also known as g2(τ), can extract meaningful information and can be calculated in at least a few ways. According to one or more aspects of the present disclosure, the intensity autocorrelation function can be calculated as follows: where I(t) is a photon count data, τ is a time lag, and the angular brackets < > denote averaging....”) (Examiner's Note: Equation 1 of Hosoda in Par. 21 of Hosoda).
Maria, Sutin, Yodh, and Hosoda are considered to be analogous art to the claimed invention as they are involved with diffuse correlation spectroscopy.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Maria, Sutin, and Yodh with that of Hosoda to include wherein the intensity auto-correlation function is determined based on an equation expressed as: (Examiner's Note: Equation of claim 5) where I(t) is intensity at the photon counting detector at time t, and I(t+τ) is intensity at the photon counting detector at time t+τ through the combination of references explicitly using the equation of Hosoda as it would have yielded the same or similar results as Maria of determining an intensity autocorrelation function, which provides meaningful information on blood flow in tissue (Hosoda (Par. 2)).
Regarding claims 14 and 23, modified Maria discloses the system of claim 5 above, which describes the methods of claim 14 and 23. As the claims are similar, claims 14 and 23 are rejected in the same manner as claim 5.
Prior Art Overcome
Regarding claims 6-7, 15-16, and 24-25 the closest prior art of record includes Maria, Sutin, Yodh, and Hosoda.
Regarding claims 6, 15, and 24 modified Maria fails to explicitly disclose the limitations of the claim.
Maria does teach estimate at least a subset of the plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions based on the modeling of the normalized intensity auto-correlation function (Par. 99-101, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999))…” (equation 5)) (Par. 101-104, “…Finally, from the five fitted parameters we can calculate μ.sub.s′ and μ.sub.a at each wavelength using Eqs. 8 and 9, as well as total hemoglobin concentration (HbT=HbO+HbR) and oxygenation (SO.sub.2=HbO/HbT).”)
However, modified Maria fails to explicitly disclose wherein the normalized intensity auto-correlation function is modeled based on an equation expressed as: (Examiner's Note: Equation of claim 6) where β is a speckle averaging factor, m is modulation depth, and g1(ρ, τ, ω=0) is a normalized electric field auto-correlation function.
However, Hosoda does teach calculating an intensity autocorrelation function (Par. 21, “Calculating the intensity autocorrelation function, also known as g2(τ), can extract meaningful information and can be calculated in at least a few ways. According to one or more aspects of the present disclosure, the intensity autocorrelation function can be calculated as follows: where I(t) is a photon count data, τ is a time lag, and the angular brackets < > denote averaging....”) (Examiner's Note: Equation 1 of Hosoda in Par. 21 of Hosoda).
However, Hosoda fails to teach the use of the exact equation of claim 6 with the specified variables.
The prior art of record fails to explicitly disclose “wherein the normalized intensity auto-correlation function is modeled based on an equation expressed as…” (Examiner's Note: Equation of claim 6) “…where β is a speckle averaging factor, m is modulation depth, and g1(ρ, τ, ω=0) is a normalized electric field auto-correlation function”.
Regarding claims 7, 16, and 25 modified Maria fails to explicitly disclose the limitations of the claim.
Maria does teach estimate at least a subset of the plurality of properties of the tissue sample using the plurality of intensity auto-correlation functions based on the modeling of the normalized intensity auto-correlation function (Par. 99-101, “DCS measures the normalized intensity autocorrelation function (g.sub.2), while the correlation diffusion equation applies to the electric field autocorrelation function. To fit the theory to the experimental data, the normalized intensity autocorrelation function must be related to the normalized electric field temporal autocorrelation (g.sub.1) through the Siegert relation (see, P. A. Lemieux and D. J. Durian “Investigating non-gaussian scattering processes by using nth-order intensity correlation functions,” Journal of the Optical Society of America A, vol. 16, pp. 1651-64 (1999))…” (equation 5)) (Par. 101-104, “…Finally, from the five fitted parameters we can calculate μ.sub.s′ and μ.sub.a at each wavelength using Eqs. 8 and 9, as well as total hemoglobin concentration (HbT=HbO+HbR) and oxygenation (SO.sub.2=HbO/HbT).”)
However, modified Maria fails to explicitly disclose wherein the normalized intensity auto-correlation function is modeled based on an equation expressed as: (Examiner's Note: Equation of claim 7) where β is a speckle averaging factor, m is modulation depth, and g1dc(τ) and g1ac(τ) are normalized electric field auto-correlation functions.
However, Hosoda does teach calculating an intensity autocorrelation function (Par. 21, “Calculating the intensity autocorrelation function, also known as g2(τ), can extract meaningful information and can be calculated in at least a few ways. According to one or more aspects of the present disclosure, the intensity autocorrelation function can be calculated as follows: where I(t) is a photon count data, τ is a time lag, and the angular brackets < > denote averaging....”) (Examiner's Note: Equation 1 of Hosoda in Par. 21 of Hosoda).
However, Hosoda fails to teach the use of the exact equation of claim 7 with the specified variables.
The prior art of record fails to explicitly disclose “wherein the normalized intensity auto-correlation function is modeled based on an equation expressed as…” (Examiner's Note: Equation of claim 7) “…where β is a speckle averaging factor, m is modulation depth, and g1dc(τ) and g1ac(τ) are normalized electric field auto-correlation functions”.
Conclusion
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/ARI S PADDA/ Examiner, Art Unit 3791
/JASON M SIMS/ Supervisory Patent Examiner, Art Unit 3791
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