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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/20/2026 has been entered.
Response to Amendment
The amendment filed on 07/20/2026 has been entered. Claims 1, 3, 4, 6, 10 and 18 have been amended. Claims 1-11 and 13-18 remain pending.
The previously raised rejections under 35 U.S.C. 112(a) for Claims 1-11 and 13-18 are withdrawn because the issues have been properly corrected.
The previously raised rejections under 35 U.S.C. 112(b) for Claims 1-11 and 13-18 are withdrawn because the issues have been properly corrected.
The previously raised rejection under 35 U.S.C. 101 for Claim 18, regarding its previous issue of software per se, is withdrawn because the issue has been properly corrected.
Response to Arguments
Rejections under 35 USC § 101
On Page 11 of Remarks, Applicant argues that the claimed operations involve physical optical signals generated through interaction of a specific wavelength of radiation with biological tissue, which cannot be practically performed in the human mind. Examiner respectfully disagrees. The procedure of emitting light to biological tissue and then receiving reflected or transmitted signal is routinely used in the field of optical imaging, and the features are recited at a high level of generality, e.g. without specialized component or step, so can be regarded as insignificant extra-solution activities.
On Page 11 of Remarks, Applicant argues that the amended claims recite selecting a specific wavelength “such that a difference in absorbance between a first portion of the biological tissue and a second portion of the biological tissue produces a difference in the degree of focusing within the measurement image”, so “recite a specific technique for processing and analyzing mid-infrared image data to identify biological tissue”. Examiner respectfully disagrees. The recited “the specific wavelength is selected such that …” is not specific, or specifically, the selecting process is not specified. A tissue sample to be examined can be fully healthy, or partially contains cancerous tissue, or contains unpredicted types of cancer, or degree of severity of cancer varies. How should the specific wavelength be selected for all these different scenarios, so that a difference in absorbance between different portions of the tissue exists? Furthermore, such as a difference in absorbance may not necessarily lead to a difference in the claimed degree of focusing in the measurement image. Examples 1 and 2 of Specification show that diseased tissue has lower level of focusing measure than normal tissue, and Example 3 instead shows that diseased tissue has higher level of focusing measure than normal tissue. In other words, the relationship between tissue type and level of focusing measure has not been established yet, or may not even exist.
On Pages 11-12 of Remarks, Applicant argues that the claims perform imaging and analysis at a single wavelength and identifying tissue based on focusing measures, and such a method significantly reduces measurement time and computational complexity and enables real-time diagnosis, thus reciting a specific improvement in the field. Examiner respectfully disagrees. First, regarding argument on “identifying tissue based on focusing measures”, the recited “focusing measures” is obtained based on edge analysis so is essentially a degree of gradient or heterogeneity, and such a measure is widely used in image processing for medical diagnosis and should not be regarded as an improvement in the field. Second, using a single wavelength does reduce measurement time and computational complexity as compared to hyperspectral imaging, but this is a widely known fact and should not be regarded as an improvement in the field. The cited reference Kroeger (US 10317655 B2) discloses that reducing the number of acquired images proportionally reduces measurement time (Column 16, Para 3), and images acquired at a single wavelength are useful in differentiating different tissue types (Column 22, Para 3).
Rejections under 35 USC § 103
On Page 13 of Remarks, Applicant argues that even though reference Kroeger discloses acquiring and analyzing images at a single wavelength, the reference does not discard hyperspectral acquisition in favor of single-wavelength imaging. Examiner respectfully disagrees. Kroeger focuses on spectral imaging that acquires at least 2 images, but in the disclosure, discloses two facts that are important to current application: 1) reducing number of wavelength or images would reduce measurement time; 2) images acquired at a single wavelength would be sufficient to identify different tissue substructures (Column 22, Para 3). Kroeger clearly discloses at least in Column 22, Para 3 that both images of a single wavelength and of 2 or more wavelengths can be used for tissue identification, but using images of more wavelength would result in more tissue substructures to be identified. To one of ordinary skill in the field, if only a binary diagnosis of normal vs cancer is to be made, one is naturally motivated to analyze images of a single wavelength as Kroeger discloses.
On Pages 13-14 of Remarks, Applicant argues that reference Takeo’s disclosed degree of gradient-vector convergence is different from the claimed degree of focusing. Examiner respectfully disagrees. In Specification, the claimed “focusing measure” is specified as being calculated by edge analysis, which is performed by differentiation filtering [0011] [0042] [0052] [0054], and such focusing measure is claimed for “representing degree of focusing”. As discussed in previous OC, that method that Takeo discloses can be interpreted as edge analysis or differentiation filter.
On Page 14 of Remarks, Applicant argues that Takeo does not teach the newly added feature of “the specific wavelength λ1 is selected such that …”. This argument is moot in view of the new grounds of rejection which relies on reference Kroeger-Lui to disclose these limitations in the claims.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-11 and 13-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
With regard to Claims 1-9 and 18:
Step 1: the claims are drawn to a method/process, one of the four statutory categories.
Step 2A, Prong One:
The claims recite the limitations of “calculating focusing measures … by an edge analysis” and “identifying the biological tissue …” in Claims 1 and 18, “the edge analysis is performed by differentiation filtering …” in Claim 2, “determining whether or not the biological tissue is a normal tissue” and “… a normal tissue is determined based on a magnitude relationship between the focusing measure and a predetermined threshold” in Claim 8, and “identifying whether or not the biological tissue contains cancer” in Claim 9, which are, under their broadest reasonable interpretation, limitations that cover performance of the limitations in the mind, and/or mathematical calculations. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind and/or mathematical calculations, then it falls within the “Mental Processes” or “Mathematical Concepts” grouping of abstract ideas. Accordingly, the claims recite an abstract idea.
Step 2A, Prong Two:
This judicial exception is not integrated into a practical application. In particular, the claims recite the additional elements – irradiating tissue with light in Claims 1, 3, 7 and 18, acquiring image of tissue after light irradiation in Claims 1 and 18, using laser light in Claim 4, performing focusing adjustment in Claim 5 and Claim 6, and selecting a wavelength in Claims 1 and 18. The laser light, wavelength selection, light irradiation, image acquisition and focusing adjustment are recited at a high-level of generality (i.e., using a generic laser-light source to image a tissue sample) such that they amount no more than mere instructions to apply the exception using a generic laser-light imaging apparatus. Accordingly, these additional elements do not integrate the abstract idea into a practical application because they do not impose any meaningful limits on practicing the abstract idea. The claims are directed to an abstract idea.
Step 2B:
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea into a practical application, the additional elements of irradiating tissue sample with laser light, wavelength selection, focusing adjustment, and acquiring an image amount to no more than mere instructions to apply the exception using a generic laser-light imaging apparatus. Mere instructions to apply an exception using a generic laser-light imaging apparatus cannot provide an inventive concept.
For the reasons set forth above, Claims 1-9 and 18 are not patent eligible.
With regard to Claims 10-11 and 13-17:
Step 1: the claims are drawn to an apparatus/device, one of the four statutory categories.
Step 2A, Prong One:
The claims recite the limitations of “a calculation analysis unit capable of calculating focusing measures … by an edge analysis …; and identifying the biological tissue …” in Claim 10, “subjecting the measurement image to differentiation filtering …” in Claim 11, and “determining whether or not the biological tissue is a normal tissue; and … a normal tissue is identified based on a magnitude relationship between the focusing measure and a predetermined threshold” in Claim 13, which are, under their broadest reasonable interpretation, limitations that cover performance of the limitations in the mind, and/or mathematical calculations. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind and/or mathematical calculations but for the recitation of generic computer components (i.e. “a computer including a calculation analysis unit”), then it falls within the “Mental Processes” or “Mathematical Concepts” grouping of abstract ideas. Accordingly, the claims recite an abstract idea.
Step 2A, Prong Two:
This judicial exception is not integrated into a practical application. In particular, the claims recite the additional elements – a light source, an imaging element and selecting a wavelength in Claim 10, an image forming unit for mapping the focusing measures in Claim 14, laser light sources in Claims 15-16, and a storage unit for storing a program for calculating focusing measures in Claim 17. The laser light sources, the imaging element, the image forming unit, the storage unit, and selecting a wavelength are recited at a high-level of generality (i.e., a generic laser-light imaging device with light irradiation and detection capability, and a generic computer with displaying and storage capability) such that they amount no more than mere instructions to apply the exception using a generic laser-light imaging device coupled with a generic computer. Accordingly, these additional elements do not integrate the abstract idea into a practical application because they do not impose any meaningful limits on practicing the abstract idea. The claims are directed to an abstract idea.
Step 2B:
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea into a practical application, the additional elements of laser light sources, imaging element, image forming unit, storage unit, and selecting a wavelength amount to no more than mere instructions to apply the exception using a generic laser-light imaging device coupled with a generic computer. Mere instructions to apply an exception using a generic laser-light imaging device and a generic computer cannot provide an inventive concept.
For the reasons set forth above, Claims 10-11 and 13-17 are not patent eligible.
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.
Claims 1-11 and 13-18 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 1, 10 and 18 recite “wherein the specific wavelength λ1 is selected such that a difference in absorbance between a first portion of the biological tissue and a second portion of the biological tissue produces a difference in the degree of focusing within the measurement image”. Specification does not provide details on how the selecting process is performed, specifically, how the recited “specific wavelength λ1” and/or “difference in absorbance” would impact the recited “difference in the degree of focusing”. For present purposes of examination, the recited phrase is interpreted to be “wherein the specific wavelength λ1 is selected to result in a difference in absorbance between a first portion of the biological tissue and a second portion of the biological tissue”.
Claims 2-9, 11, and 13-17 are also rejected under 35 U.S.C. 112(a) because they inherit the deficiencies of the claim(s) they respectively depend upon.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-5, 8-11 and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Kroeger-Lui (US 10317655 B2; hereafter Kroeger), in view of Takeo et al (US 20040081343 A1; hereafter Takeo).
With regard to Claim 1, Kroeger discloses a method for identifying a biological tissue (Kroeger, Column 2, Para 3; “… cost-effective and rapid IR analysis devices and methods, in particular for examining biological samples”), the method comprising:
irradiating a predetermined region of the biological tissue with a measurement light having a specific wavelength λ1 in a range of 2 μm to 20 μm (Kroeger, Column 2, Para 5; “… comprising the steps of irradiating the sample with an infrared (IR) radiation …”; Column, Para 21; “…is sufficient for the analysis of the middle infrared spectrum of thin tissue sections.”) (Kroeger, Column 7, Para 5; “In a preferred embodiment, the IR radiation emitted by the QCL is in a range from 5 to 12.5 μm.”);
acquiring a measurement image (Kroeger, Column 4, Para 5; “… hyperspectral imagings of a sample with a spatial resolution of less than 20 μm are possible as a result of the high measurement accuracy.”; multiple disclosures in Kroeger indicate that images of individual wavelength are available as the outcome of image acquisition) by imaging the measurement light having the specific wavelength λ1 transmitted through the biological tissue or reflected at the biological tissue (Kroeger, Column 2, Para 4; “… a sensor which detects an IR radiation which is transmitted and/or reflected by the sample …”);
identifying the biological tissue (Kroeger, Column 17, Para 3; “… in the case of a tissue sample the arrangement and the state of the cells and other tissue structures (for example, connective tissue) can be identified.”); and
wherein the specific wavelength λ1 is selected such that a difference in absorbance between a first portion of the biological tissue and a second portion of the biological tissue produces a difference in the degree of focusing within the measurement image (Kroeger, Column 22, Lines 31-38; “The analysis of a single wavelength was already sufficient to obtain a first impression of the quality of the imaging obtained. The recording of the infrared transmission at 1218 cm-1 (±1.2 cm-1) over the complete large intestine section clearly showed the central lumen surrounded by large intestine epithelium and muscle tissue (Lamina muscularis mucosae). By digital zoom, the substructure of the epithelium could also be identified.” This disclosure indicates that absorbance of light at wavelength of 1218 cm-1 or 8.2 micrometer is different between the substructure of the epithelium and muscle tissue).
Kroeger does not clearly and explicitly disclose:
calculating focusing measures in a plurality of regions of the measurement image by an edge analysis of the measurement image, the focusing measures representing a degree of focusing of the measurement image; and
identifying the biological tissue based on the focusing measures.
Takeo in the same field of endeavor discloses:
calculating focusing measures in a plurality of regions of the measurement image (Takeo, Para 0076; “… for each pixel among all of the pixels constituting the given image, the pixel is taken as a pixel of interest, and the degree of convergence C of the gradient vectors with respect to the pixel of interest is calculated with Formula (2) shown below”) by an edge analysis of the measurement image, the focusing measures representing a degree of focusing of the measurement image (Takeo, Para 0073; “For each pixel j among all of the pixels constituting a given image, the orientation θ of the gradient vector of the image signal representing the image is calculated with Formula (1) shown below”; Para 0069 “The iris filter calculates the gradients of image signal values … as gradient vectors and feeds out the information representing the degree of convergence of the gradient vectors. With the iris filtering processing a tumor pattern is detected in accordance with the degree of convergence of the gradient vectors”; Para 0078; “the processing with the iris filter has the features over an ordinary difference filter in that the processing with the iris filter is not apt to be adversely affected by blood vessel patterns, mammary gland patterns, or the like, and can efficiently detect tumor patterns”. These disclosures of Takeo indicates that the method of Takeo can be interpreted as an edge analysis); and
identifying the biological tissue based on the focusing measures (Takeo, Para 0185; “… an image area, which is associated with a high degree of convergence of image density gradient vectors, is detected as a temporary candidate for an abnormal pattern (a tumor pattern)”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger, as suggested by Takeo, in order to compute a measure based on edge analysis and use it for identifying biological tissue. One of ordinary skill in the art would have been motivated to make the modification for the benefit of improved capability of detecting tissue abnormality by identifying characteristic gradient or edge patterns of tumors (Takeo, Para 0068; “It has been known that … in the tumor pattern, the gradients of the image density values can be found in local areas, and the gradient lines (i.e., gradient vectors) converge in the directions heading toward the center point of the tumor pattern.”).
With regard to Claim 2, Kroeger and Takeo disclose all the limitations of Claim 1 as discussed above, but do not clearly and explicitly disclose wherein the edge analysis is performed by differentiation filtering of the measurement image.
Takeo further discloses wherein the edge analysis is performed by differentiation filtering of the measurement image (Takeo, Para 0073; “For each pixel j among all of the pixels constituting a given image, the orientation θ of the gradient vector of the image signal representing the image is calculated with Formula (1) shown below: θ = tan-1 [( f3 + f4 + f5 + f6 + f7) - ( f11 + f12 + f13 + f14 + f15 )/[( f1 + f2 + f3 + f15 + f16 ) - ( f7 + f8 + f9 + f10 + f11 )”. Here the equation of gradient vector involves applying discrete differentiation for each pixel of an image, i.e. a type of differentiation filtering). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to use differentiation filtering for edge analysis. One of ordinary skill in the art would have been motivated to make the modification for the benefit of efficiently extracting edge- or gradient-related information from images.
With regard to Claim 3, Kroeger and Takeo disclose all the limitations of Claim 1 as discussed above. Kroeger further discloses wherein the biological tissue is irradiated with laser light having a wavelength λ1 as the measurement light (Kroeger, Abstract; “having a beam path having at least one quantum cascade laser (QCL) (3) which emits an infrared (IR) radiation … detects an IR radiation which is transmitted and/or reflected by the sample (2) …”).
With regard to Claim 4, Kroeger and Takeo disclose all the limitations of Claim 3 as discussed above. Kroeger further discloses wherein the measurement light is quantum cascade laser light or laser light amplified by optical parametric oscillation (Kroeger, Abstract; “having a beam path having at least one quantum cascade laser (QCL) (3) which emits an infrared (IR) radiation …”).
With regard to Claim 5, Kroeger and Takeo disclose all the limitations of Claim 1 as discussed above. Kroeger further discloses wherein focusing adjustment is performed before the measurement image is acquired (Kroeger, Column 16, Para 5; “the method further comprises the step of focusing the sample in accordance with the wavelength of the IR radiation of the QCL.” Column 17, Para 2; “In this manner, it is ensured that the sample for each wavelength is sharply imaged on the detector.”).
With regard to Claim 8, Kroeger and Takeo disclose all the limitations of Claim 1 as discussed above. Kroeger further discloses wherein the identification of the biological tissue based on the focusing measures includes determining whether or not the biological tissue is a normal tissue (Kroeger, Column 1, Para 2; “… changes of the tissue which are triggered by different organic malfunctions can lead to similar or even identical symptoms.”; Column 17, Para 3; “… in the case of a tissue sample the arrangement and the state of the cells and other tissue structures (for example, connective tissue) can be identified.”. The disclosed identification of arrangement and state of cells and tissue structures would enable determination on whether the tissue is normal or not).
Kroeger and Takeo as discussed above do not clearly and explicitly disclose wherein whether or not the biological tissue is a normal tissue is determined based on a magnitude relationship between the focusing measures and a predetermined threshold.
Takeo further discloses wherein whether or not the biological tissue is a normal tissue is determined based on a magnitude relationship between the focusing measures and a predetermined threshold (Takeo, Para 0078; “… a tumor pattern can be detected by …, and rating whether the value of the degree of convergence C is or is not larger than a predetermined threshold value”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to identify normal tissue based on the magnitude of the focusing measure. One of ordinary skill in the art would have been motivated to make the modification for the benefit of determining a tissue to be normal or without tumor in an objective and efficient manner (Takeo, Para 0078; “… the processing with the iris filter has the features over an ordinary difference filter in that the processing with the iris filter is not apt to be adversely affected by blood vessel patterns, mammary gland patterns, or the like, and can efficiently detect tumor patterns.”).
With regard to Claim 9, Kroeger and Takeo disclose all the limitations of Claim 1 as discussed above, but do not clearly and explicitly disclose wherein the identification of the biological tissue based on the focusing measures includes determining whether or not the biological tissue contains cancer.
Takeo further discloses wherein the identification of the biological tissue based on the focusing measures includes determining whether or not whether or not the biological tissue contains cancer (Takeo, Para 0078; “… a tumor pattern can be detected by …, and rating whether the value of the degree of convergence C is or is not larger than a predetermined threshold value”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to detect cancer based on the magnitude of the focusing measure. One of ordinary skill in the art would have been motivated to make the modification for the benefit of detecting tumor regions in an objective and efficient manner (Takeo, Para 0078; “… the processing with the iris filter has the features over an ordinary difference filter in that the processing with the iris filter is not apt to be adversely affected by blood vessel patterns, mammary gland patterns, or the like, and can efficiently detect tumor patterns.”).
With regard to Claim 10, Kroeger discloses a biological tissue identification apparatus (Kroeger, Abstract; “… a microscope for the molecular spectroscopic analysis of a sample (2) …”) comprising:
a light source (Kroeger, Abstract; “… having at least one quantum cascade laser (QCL) (3) which emits an infrared (IR) radiation …”) capable of irradiating a predetermined region of a biological tissue with a measurement light having a specific wavelength λ1 in a range of 2 μm to 20 μm (Kroeger, Column 2, Para 5; “… comprising the steps of irradiating the sample with an infrared (IR) radiation …”; Column, Para 21; “…is sufficient for the analysis of the middle infrared spectrum of thin tissue sections.”) (Kroeger, Column 7, Para 5; “In a preferred embodiment, the IR radiation emitted by the QCL is in a range from 5 to 12.5 μm.”);
an imaging element (Kroeger, Abstract; “… and a sensor (4) which detects an IR radiation …”) for acquiring a measurement image (Kroeger, Column 4, Para 5; “… hyperspectral imagings of a sample with a spatial resolution of less than 20 μm are possible as a result of the high measurement accuracy.”; multiple disclosures in Kroeger indicate that images of individual wavelength are available as the outcome of image acquisition) by imaging the mid-infrared measurement light having a specific wavelength λ1 transmitted through the biological tissue or the measurement light reflected at the biological tissue (Kroeger, Column 2, Para 4; “… a sensor which detects an IR radiation which is transmitted and/or reflected by the sample …”); and
a computer including a calculation analysis unit (Kroeger, Column 2, Para 3; “… a need for cost-effective and rapid IR analysis devices”. This disclosure does not explicitly disclos such a unit or device, but in its motivation indicates that such device based on the disclosed method, including tissue identification, are needed) capable of identifying the biological tissue (Kroeger, Column 17, Para 3; “… in the case of a tissue sample the arrangement and the state of the cells and other tissue structures (for example, connective tissue) can be identified.”); and
wherein the specific wavelength λ1 is selected such that a difference in absorbance between a first portion of the biological tissue and a second portion of the biological tissue produces a difference in the degree of focusing within the measurement image (Kroeger, Column 22, Lines 31-38; “The analysis of a single wavelength was already sufficient to obtain a first impression of the quality of the imaging obtained. The recording of the infrared transmission at 1218 cm-1 (±1.2 cm-1) over the complete large intestine section clearly showed the central lumen surrounded by large intestine epithelium and muscle tissue (Lamina muscularis mucosae). By digital zoom, the substructure of the epithelium could also be identified.” This disclosure indicates that absorbance of light at wavelength of 1218 cm-1 or 8.2 micrometer is different between the substructure of the epithelium and muscle tissue).
Kroeger does not explicitly and clearly disclose:
calculating focusing measures in a plurality of regions of the measurement image by an edge analysis of the measurement image, the focusing measures representing a degree of focusing of the measurement image; and
identifying the biological tissue based on the focusing measures.
Takeo in the same field of endeavor discloses calculating focusing measures in a plurality of regions of the measurement image (Takeo, Para 0076; “… for each pixel among all of the pixels constituting the given image, the pixel is taken as a pixel of interest, and the degree of convergence C of the gradient vectors with respect to the pixel of interest is calculated with Formula (2) shown below”) by an edge analysis of the measurement image, the focusing measures representing a degree of focusing of the measurement image (Takeo, Para 0073; “For each pixel j among all of the pixels constituting a given image, the orientation θ of the gradient vector of the image signal representing the image is calculated with Formula (1) shown below”; Para 0069 “The iris filter calculates the gradients of image signal values … as gradient vectors and feeds out the information representing the degree of convergence of the gradient vectors. With the iris filtering processing a tumor pattern is detected in accordance with the degree of convergence of the gradient vectors”; Para 0078; “the processing with the iris filter has the features over an ordinary difference filter in that the processing with the iris filter is not apt to be adversely affected by blood vessel patterns, mammary gland patterns, or the like, and can efficiently detect tumor patterns”. These disclosures of Takeo indicates that the method of Takeo can be interpreted as an edge analysis); and
identifying the biological tissue based on the focusing measures (Takeo, Para 0185; “… an image area, which is associated with a high degree of convergence of image density gradient vectors, is detected as a temporary candidate for an abnormal pattern (a tumor pattern)”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger, as suggested by Takeo, in order to compute a measure based on edge analysis and use it for identifying biological tissue. One of ordinary skill in the art would have been motivated to make the modification for the benefit of improved capability of detecting tissue abnormality by identifying characteristic gradient or edge patterns of tumors (Takeo, Para 0068; “It has been known that … in the tumor pattern, the gradients of the image density values can be found in local areas, and the gradient lines (i.e., gradient vectors) converge in the directions heading toward the center point of the tumor pattern.”).
With regard to Claim 11, Kroeger and Takeo disclose all the limitations of Claim 10 as discussed above, but do not clearly and explicitly disclose wherein the calculation analysis unit calculates the focusing measures by subjecting the measurement image to differentiation filtering.
Takeo further discloses wherein the calculation analysis unit calculates the focusing measures by subjecting the measurement image to differentiation filtering (Takeo, Para 0073; “For each pixel j among all of the pixels constituting a given image, the orientation θ of the gradient vector of the image signal representing the image is calculated with Formula (1) shown below: θ = tan-1 [( f3 + f4 + f5 + f6 + f7) - ( f11 + f12 + f13 + f14 + f15 )/[( f1 + f2 + f3 + f15 + f16 ) - ( f7 + f8 + f9 + f10 + f11 )”. Here the equation of gradient vector involves applying discrete differentiation for each pixel of an image, i.e. a type of differentiation filtering). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to use differentiation filtering to compute focusing measure. One of ordinary skill in the art would have been motivated to make the modification for the benefit of extracting the gradient-related information that would enable improved differentiation capability of the characteristic patterns of different tissue types (Takeo, Para 0068; “It has been known that … in the tumor pattern, the gradients of the image density values can be found in local areas, and the gradient lines (i.e., gradient vectors) converge in the directions heading toward the center point of the tumor pattern.”).
With regard to Claim 13, Kroeger and Takeo disclose all the limitations of Claim 10 as discussed above. Kroeger further discloses wherein in the calculation analysis unit, the identification of the biological tissue based on the focusing measures includes determining whether or not the biological tissue is a normal tissue (Kroeger, Column 1, Para 2; “… changes of the tissue which are triggered by different organic malfunctions can lead to similar or even identical symptoms.”; Column 17, Para 3; “… in the case of a tissue sample the arrangement and the state of the cells and other tissue structures (for example, connective tissue) can be identified.”. The disclosed identification of arrangement and state of cells and tissue structures would enable determination on whether the tissue is normal or not).
Kroeger and Takeo as discussed above do not clearly and explicitly disclose wherein whether or not the biological tissue is a normal tissue is determined based on a magnitude relationship between the focusing measures and a predetermined threshold.
Takeo further discloses wherein whether or not the biological tissue is a normal tissue is determined based on a magnitude relationship between the focusing measures and a predetermined threshold (Takeo, Para 0078; “… a tumor pattern can be detected by …, and rating whether the value of the degree of convergence C is or is not larger than a predetermined threshold value”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to identify normal tissue based on the magnitude of the focusing measure. One of ordinary skill in the art would have been motivated to make the modification for the benefit of determining a tissue to be normal or without tumor in an objective and efficient manner (Takeo, Para 0078; “… the processing with the iris filter has the features over an ordinary difference filter in that the processing with the iris filter is not apt to be adversely affected by blood vessel patterns, mammary gland patterns, or the like, and can efficiently detect tumor patterns.”).
With regard to Claim 14, Kroeger and Takeo disclose all the limitations of Claim 10 as discussed above, but do not clearly and explicitly disclose wherein the computer includes an image forming unit for mapping the focusing measures to form an analysis image.
Takeo further discloses wherein the computer includes an image forming unit for mapping the focusing measures to form an analysis image (Takeo, Para 0122; “… a peripheral edge image (the IFED image) is formed by the utilization of the iris filtering processing.”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to form a map of the focusing measures. One of ordinary skill in the art would have been motivated to make the modification for the benefit of visualizing pattern or texture in an image so as to detect abnormal tissues quickly.
With regard to Claim 15, Kroeger and Takeo disclose all the limitations of Claim 10 as discussed above. Kroeger further discloses wherein the light source is a laser light source capable of scanning wavelengths (Kroeger, Column 21, Para 4; “there were used two quantum cascade lasers (Daylight Solutions Inc., USA) which could be tuned over 1027 to 1087 cm-1 and 1167 to 1319 cm-1 (corresponds to a wavelength range of 9.74 μm to 9.20 μm and 8.57 μm to 7.58 μm).” This disclosure discloses light sources that generate laser of tunable wavelength, so can be regarded as being capable of scanning wavelengths).
With regard to Claim 16, Kroeger and Takeo disclose all the limitations of Claim 10 as discussed above. Kroeger further discloses wherein the light source is a source of quantum cascade laser or a laser source including an optical parametric oscillator (Kroeger, Abstract; “having a beam path having at least one quantum cascade laser (QCL) (3) which emits an infrared (IR) radiation …”).
With regard to Claim 17, Kroeger and Takeo disclose all the limitations of Claim 10 as discussed above, including the calculation analysis unit to execute processing in which the measurement image acquired by the imaging element is subjected to edge analysis to calculate the focusing measures in the plurality of regions of the measurement image. Kroeger and Takeo as discussed above do not explicitly and clearly disclose wherein a program for causing to executing the processing is stored in a storage unit of the computer.
Takeo further discloses wherein a program for causing unit to execute the processing is stored in a storage unit of the computer (Takeo, Para 0184; “The abnormal pattern candidate detection processing system 100 comprises abnormal pattern candidate detecting means 10 …”; Para 0185; “The abnormal pattern candidate detecting means 10 stores an algorithm for abnormal pattern candidate detection processing utilizing an iris filter …”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as further suggested by Takeo, in order to store the program for the proposed processing in the storage unit of the computer of the system. One of ordinary skill in the art would have been motivated to make the modification for the benefit of performing the processing locally in real time and therefore achieving diagnosis with high efficiency.
With regard to Claim 18, Kroeger discloses a non-transitory computer readable medium on which a biological tissue identification program for identifying a biological tissue is stored (Kroeger, Column 17, Para 1; “computer unit”, which inherently comprises a medium for storing programs), the biological tissue identification program (Kroeger, Column 2, Para 3; “… cost-effective and rapid IR analysis devices and methods, in particular for examining biological samples”. To one of ordinary skill in the art, the methods and their implementation in devices are inherently in the form of programs) comprising a processing procedure for causing a computer to execute the steps of:
irradiating a predetermined region of the biological tissue with a measurement light having a specific wavelength λ1 in a range of 2 μm to 20 μm (Kroeger, Column 2, Para 5; “… comprising the steps of irradiating the sample with an infrared (IR) radiation …”; Column, Para 21; “…is sufficient for the analysis of the middle infrared spectrum of thin tissue sections.”) (Kroeger, Column 7, Para 5; “In a preferred embodiment, the IR radiation emitted by the QCL is in a range from 5 to 12.5 μm.”);
acquiring a measurement image (Kroeger, Column 4, Para 5; “… hyperspectral imagings of a sample with a spatial resolution of less than 20 μm are possible as a result of the high measurement accuracy.”; multiple disclosures in Kroeger indicate that images of individual wavelength are available as the outcome of image acquisition) by imaging the measurement light transmitted through the biological tissue or the measurement light reflected at the biological tissue (Kroeger, Column 2, Para 4; “… a sensor which detects an IR radiation which is transmitted and/or reflected by the sample …”);
identifying the biological tissue (Kroeger, Column 17, Para 3; “… in the case of a tissue sample the arrangement and the state of the cells and other tissue structures (for example, connective tissue) can be identified.”), wherein the specific wavelength λ1 is selected such that a difference in absorbance between a first portion of the biological tissue and a second portion of the biological tissue produces a difference in the degree of focusing within the measurement image (Kroeger, Column 22, Lines 31-38; “The analysis of a single wavelength was already sufficient to obtain a first impression of the quality of the imaging obtained. The recording of the infrared transmission at 1218 cm-1 (±1.2 cm-1) over the complete large intestine section clearly showed the central lumen surrounded by large intestine epithelium and muscle tissue (Lamina muscularis mucosae). By digital zoom, the substructure of the epithelium could also be identified.” This disclosure indicates that absorbance of light at wavelength of 1218 cm-1 or 8.2 micrometer is different between the substructure of the epithelium and muscle tissue).
Kroeger does not clearly and explicitly disclose:
calculating focusing measures in a plurality of regions of the measurement image by an edge analysis of the measurement image, the focusing measures representing a degree of focusing of the measurement image; and
identifying the biological tissue based on the focusing measures.
Takeo in the same field of endeavor discloses:
calculating focusing measures in a plurality of regions of the measurement image (Takeo, Para 0076; “… for each pixel among all of the pixels constituting the given image, the pixel is taken as a pixel of interest, and the degree of convergence C of the gradient vectors with respect to the pixel of interest is calculated with Formula (2) shown below”) by an edge analysis of the measurement image, the focusing measures representing a degree of focusing of the measurement image (Takeo, Para 0073; “For each pixel j among all of the pixels constituting a given image, the orientation θ of the gradient vector of the image signal representing the image is calculated with Formula (1) shown below”; Para 0069 “The iris filter calculates the gradients of image signal values … as gradient vectors and feeds out the information representing the degree of convergence of the gradient vectors. With the iris filtering processing a tumor pattern is detected in accordance with the degree of convergence of the gradient vectors”; Para 0078; “the processing with the iris filter has the features over an ordinary difference filter in that the processing with the iris filter is not apt to be adversely affected by blood vessel patterns, mammary gland patterns, or the like, and can efficiently detect tumor patterns”. These disclosures of Takeo indicates that the method of Takeo can be interpreted as an edge analysis); and
identifying the biological tissue based on the focusing measures (Takeo, Para 0185; “… an image area, which is associated with a high degree of convergence of image density gradient vectors, is detected as a temporary candidate for an abnormal pattern (a tumor pattern)”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger, as suggested by Takeo, in order to compute a measure based on edge analysis and use it for identifying biological tissue. One of ordinary skill in the art would have been motivated to make the modification for the benefit of improved capability of detecting tissue abnormality by identifying characteristic gradient or edge patterns of tumors (Takeo, Para 0068; “It has been known that … in the tumor pattern, the gradients of the image density values can be found in local areas, and the gradient lines (i.e., gradient vectors) converge in the directions heading toward the center point of the tumor pattern.”).
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Kroeger and Takeo, in view of Domenicali (US 20090096914 A1; hereafter Domenicali) and Grimbergen et al (US 20180259848 A1; hereafter Grimbergen).
With regard to Claim 6, Kroeger and Takeo disclose all the limitations of Claim 5 as discussed above. Kroeger further discloses wherein in the focusing adjustment,
the predetermined region of the biological tissue is irradiated with the measurement light (Kroeger, Column 16, Para 5; “An adaptation of the focus in accordance with the wavelength of the QCL is consequently advantageous. This can be carried out, for example, by the synchronised displacement of the sample or the detector.” In this disclosure, irradiation of the measurement light onto the sample is the first step, followed by the “adaption of the focus”.),
light having wavelength in a range of 2 μm to 20 μm is used (Kroeger, Column 16, Para 5; “An adaptation of the focus in accordance with the wavelength of the QCL is consequently advantageous.” This disclosure indicates that the focusing adjustment is based on the measurement QCL, the wavelength of which is in the range of 2-20 μm as disclosed in the reference.), and
a position of a sample containing the biological tissue and/or a position of another optical element is adjusted (Kroeger, Column 16, Para 5; “This can be carried out, for example, by the synchronised displacement of the sample or the detector. … In order to position the detector or the sample in accordance with the wavelength emitted by the QCL, the position thereof can be controlled by means of a computer unit.”) so that the degree of focusing of the focusing adjusting image increases (Kroeger, Column 16, Para 5; “In this manner, it is ensured that the sample for each wavelength is sharply imaged on the detector.”).
Kroeger and Takeo do not explicitly and clearly disclose wherein a focusing adjusting image is acquired by imaging light having wavelength λ0, and wherein the wavelength λ0 is different from the wavelength λ1.
Domenicali in the same field of endeavor discloses wherein a focusing adjusting image is acquired (Domenicali, Para 0051; “The position of the optical element can be adjusted to maintain a focus of the image in response to the wavelength band selection.” The reference discloses a dynamic focusing adjustment procedure, so that images are formed in the procedure of focusing). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger and Takeo, as suggested by Domenicali, in order to form an image with the focusing-adjustment light. One of ordinary skill in the art would have been motivated to make the modification for the benefit of visualizing the outcome of focusing adjustment in a real-time manner so as to determine whether more adjustment is needed.
Kroeger, Takeo and Domenicali do not explicitly and clearly disclose using a focusing-adjusting light with different wavelength as the measurement light.
Grimbergen in the same field of endeavor discloses using a focusing-adjusting light with different wavelength as the measurement light (Grimbergen, Para 0007; “Focus adjustment and evaluation of the spot size and location can then be done at a single wavelength. This single wavelength can be conveniently chosen in the visible part of the spectrum for set-up, and the same focus will apply to a broad range of wavelengths …” In this disclosure, the focusing-adjustment setting at one wavelength is used for imaging of other wavelengths in a range). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kroeger, Takeo and Domenicali, as suggested by Grimbergen, in order to use a light with wavelength different from the measurement light for focusing adjustment. One of ordinary skill in the art would have been motivated to make the modification for the benefit of saving acquisition time in situations when images of multiple wavelengths (or hyperspectral imaging as termed in Kroeger) are acquired.
With regard to Claim 7, Kroeger, Takeo, Domenicali and Grimbergen discloses all the limitations of Claim 6 as discussed above, including using laser light having different wavelength from the measurement light. Kroeger further discloses wherein in the focusing adjustment, the biological tissue is irradiated with laser light having a wavelength λ0 (Kroeger, Column 16, Para 5; “An adaptation of the focus in accordance with the wavelength of the QCL is consequently advantageous.” This disclosure inherently indicates that QCL laser light is irradiated onto the tissue or sample).
Conclusion
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/L.Z./ Examiner, Art Unit 3798
/PASCAL M BUI PHO/ Supervisory Patent Examiner, Art Unit 3798
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