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 .
Response to Arguments
Applicant’s arguments, see Remarks at page 1, filed 22 August, 2025, with respect to the objection to the specification have been fully considered and are persuasive. The objection has been withdrawn.
Applicant’s arguments, see Remarks at page 2, filed 22 August, 2025, with respect to the objection to the drawings have been fully considered and are persuasive. The objection has been withdrawn.
Applicant’s arguments, see Remarks at page 2, filed 22 August, 2025, with respect to the objection to claim 5 have been fully considered and are persuasive. The objection has been withdrawn.
Applicant’s arguments, see Remarks at page 3, filed 22 August, 2025, with respect to the rejections of claims 16 and 17 under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejections have been withdrawn.
Applicant’s arguments, see Remarks at page 3, filed 22 August, 2025, with respect to the rejections of claims 13 and 16 under 35 U.S.C. 101 have been fully considered and are persuasive. The rejection has been withdrawn.
Applicant’s arguments, see Remarks at pages 4-7, filed 22 August, 2025, with respect to the rejection of claims 1-3, 6, 7, 9, 14, 15, and 17 under 35 U.S.C. 102(a)(1) as being anticipated by Gong have been fully considered but are not persuasive. Examiner respectfully disagrees for the following reasons.
At page 4 of Remarks, Applicant asserts an exception under 35 U.S.C. 102(b)(1) applies to Gong and indicates a willingness to provide a declaration to disqualify Gong as prior art. Examiner appreciates Applicant’s acknowledgement that the additional authors of the Gong reference “obtained information about the invention from the inventors of the present application” (Remarks at pg. 4). However, to provide sufficient evidence of record that an exception under 35 U.S.C. 102(b)(1) applies, Applicant is required to submit a declaration under 37 CFR 1.130. See MPEP 717, 2153.01(a), and 2155. Accordingly, until a declaration is filed, Gong remains valid prior art under 35 U.S.C. 102(a)(1).
At pages 4-5 of Remarks, Applicant argues regarding claims 1 and 14 that Gong fails to teach “comparing the tissue index to a threshold to determine a tissue type”, noting that in the Non-Final Office Action, the examiner pointed to a “Method… [of] differentiation between cancer and benign ROIs” disclosed by Gong. Applicant argues Gong’s disclosed method is not equivalent to the claim language above because the tissue type in the ROIs is already determined by a board-certified radiologist, and “[thus], Gong describes, at most, the opposite of claim 1, i.e., determining tissue type and then determining a tissue index for a predetermined tissue type”. Examiner respectfully disagrees.
The certification of benign and cancerous ROIs by a radiologist, as disclosed by Gong, may be one determination of a tissue type, but it is not the only determination. Gong also discloses generating Luminal Water Fraction (LWF) maps for each of 19 patients who supplied the multiecho MRI data and fitting the multiecho data to a simulated decay curve (See Methods section). LWF, under the broadest reasonable interpretation, is a tissue index because it reflects the ratio of free water to tissue volume, where cancerous tissues tend to have lower LWF compared to benign tissues, which tend to have higher LWF. This is reflected in Figures 2 and 3 of Gong, where Figure 2 shows high LWF (i.e., 0.84, 0.80, 0.77, 0.64) for each number of echoes and long decay tails for benign regions and Figure 3 shows low LWF (i.e., 0.06, 0.06, 0.03, 0.01) for each number of echoes. Thus, Gong calculates a plurality of tissue indices (i.e., LWF values) for 32, 16, 8, and 6 echoes.
Gong discloses comparing the LWF (tissue index) to a threshold to determine a tissue type. A purpose of Gong’s study was to investigate if fewer than 32 echoes can be used for classifying tissue as being prostate cancer or benign (See title and abstract). Using radiologist-certified ROIs of cancerous and benign prostate tissue ROIs, the ROIs are transferred to the generated LWF maps and ROC analysis is performed to evaluate the accuracy of the radiologist’s classification (See Method and Results sections). The effect of the ROC analysis is to confirm how well low LWF values correspond to a radiologist’s diagnosis of prostate cancer and how well high LWF values correspond to a radiologist’s diagnosis/classification of the tissue. This is demonstrated by Figure 4, which shows the ROC curves for each of the 32, 16, 8, and 6 echoes. The LWF is what differentiates “between cancer and benign ROIs” in Gong’s method (See Method section). Gong concludes by stating “Classification ability of quantitative LWF measurements remains good with a ROC area under curve slightly decreasing from 0.85 to 0.8 from 32 to 6 echoes” (emphasis added). This means that the LWF values/measurements are what classify/indicate the tissue type as cancer or benign. Thus, the ROC analysis shown in Figure 4 is performed to demonstrate that the LWF values in Figures 2 and 3 accurately determine the tissue type as being cancerous or benign. The ROC analysis confirms that the LWF values for fewer than 32 echoes are suitable for determining classification of prostate cancer (i.e., tissue type). Each of Figures 2 and 3 provides a comparison to the 32 echo baseline by calculating the LWF for 16, 8, and 6 echoes, where low LWF values of 0.06, 0.03, and 0.01 correspond to cancerous tissue and the significantly larger quantified values of high LWF of 0.84, 0.80, 0.77, and 0.64 correspond to non-cancerous tissue that acts as a threshold separating one classification from another. The 32 echo LWF values establish a first threshold LWF (i.e., 0.84) and a second threshold LWF (i.e., 0.06) for an exemplary patient. Generating data and graphs of Figures 2 and 3 and arranging them together is a comparison amongst the constituent parts of Figures 2 and 3. Thus, by comparing the LWF values of all different numbers of echoes to each other for both cancerous and benign T2 distributions, Gong discloses comparing the benign LWF values (i.e., tissue index) to cancerous LWF values (that serve as thresholds indicative of (i.e., differentiating) the tissue type as being cancer or not benign) and comparing the cancerous LWF values (i.e., tissue index) to benign LWF values (that serve as thresholds indicative of the tissue type being benign or not cancerous).
At pages 6-7 of Remarks, Applicant argues regarding claims 1 and 14, that the alleged deficiencies of Gong are nonobvious because “nothing in Gong [suggests] that it would be possible to compare a tissue index to a threshold to determine a tissue type from a scan of an organ, e.g., from data that has not been specifically preselected. Statements in Gong are based on specifically selected tissue regions. There is no mention in Gong even of applying a threshold to the data derived from preselected regions much less any suggestion that this could be applied to a scan of an organ of a patient as defined in present claim 1. There is a range of tissue types and structures in an organ. Whether tissue types in an organ can be determined is an entirely different application to whether two known tissue types produce different data from 31 samples that have been deliberately and specifically preselected” (original emphasis). Examiner respectfully disagrees.
The MRI data used by Gong represents/corresponds scans of patients’ prostates and the data derived and presented in Figures 1-3 represents/corresponds to an organ (prostate) of an exemplary patient. The claims do not require that the determined tissue type cannot be determined a second time to confirm a prior classification (i.e., cannot be preselected as argued by Applicant). Nor do the claims require distinguishing between a range of tissue types and structures in an organ. Rather, the claims simply require comparing an index to a threshold to determine a type of tissue, which Gong teaches as explained above. Furthermore, Gong does not merely recycle preselected data without deriving new and useful information as seemingly implied by Applicant. Rather, Gong uses preselected data as a baseline to determine if “a further reduction in echo train length is possible” (Introduction section), which is something the board-certified radiologists who provided the baseline/ground truth classification were not aware of because Gong had yet to determine if fewer echoes would be a viable option.
Applicant’s arguments, see Remarks at pages 7-10, filed 22 August, 2025, with respect to the rejection of claims 1-3, 6, 7, 9-11, and 13-17 under 25 U.S.C. 103 as being unpatentable over Devine in view of Bydder have been fully considered but are not persuasive. Examiner respectfully disagrees for the following reasons.
At pages 7-10 of Remarks, Applicant argues Devine fails to teach “comparing the tissue index to a threshold to determine a tissue type” and “instead teaches using data for which a tissue type has already been determined” (original emphasis), that FIG. 4 of Devine does not teach using any value as a threshold or “selecting any one of the values on the scale of FIG. 4 and attempting to use it as a threshold value” , which would not allow for “determination of a tissue type”, and that the color-coded LWF map showing same colors cross different pixels would “seemingly not allow determination of a tissue type.” Examiner respectfully disagrees.
Claims 1, 13, and 14 each recite, in part, “comparing the tissue index to a threshold to determine a tissue type”. As explained above, LWF values are considered index values and act as thresholds because they define a quantified difference between two types of tissue. The prior art is not required to use the exact word “threshold” to describe the concept of a threshold. Devine discloses in FIG. 4 that higher LWF values correspond to cancerous tissue and lower LWF values correspond to non-cancerous tissue. These LWF values are attributed to every pixel in the image and a color-coded scale is provided to show how the colors correspond to different LWF values. The color gradient used to label each pixel in the LWF map of FIG. 4 could not otherwise have been produced without associating every LWF value with a specific color depending on where that value lies in the range of 0 to 1. The color reflects the tissue type, where dark blue indicates low LWF values and benign tissue and yellow and orange indicate higher LWF and cancerous tissue, for example. Thus, by labeling the LWF map as shown in FIG. 4, Devine discloses comparing LWF values (i.e., original tissue indices before the color labeling) to threshold LWF values that denote specific colors corresponding to the type of tissue of each pixel, thereby determining a type of tissue as a result of the comparison. A same color in different pixels of the LWF map indicates that the same type of tissue is present in those locations. Knowing that certain areas of a prostate exhibit signs of being cancerous while other areas are benign is still quite useful because it means the organ as a whole is affected by cancer. The claims do not require making an overall classification for the entire organ based on some complex assessment of individual classifications for every pixel in an LWF map. Rather, the claims merely require determining a tissue type.
At page 9 of Remarks, Applicant argues that “no specific method for detecting and grading prostate cancer is set out in Devine”, the disclosure of “higher LWF in a peripheral zone” shown in FIG. 4 “does not relate any higher or lower value to prostate cancer” and that there is no teaching of Devine to suggest “The LWF map provides a means of ‘detecting and grading Prostate Cancer’” (original emphasis). Examiner respectfully disagrees for three reasons.
First, the peripheral zone is part of the prostate. Devine specifically refers to the peripheral zone because the color-coded LWF map shows higher LWF in the same areas of “large regular acini and loosely woven stroma” (pg. 3), thereby confirming that the color-coded LWF indicates specific areas where prostate cancer is likely.
Second, Devine discloses, “Correlations to Gleason score were then performed along with the AUC, sensitivity and specificity of the detection of PCa” (Introduction). Gleason scores rank the aggressiveness of prostate cancer.1 By stating “multi-echo T2 modelling shows promise in detecting and grading PCa” (Synopsis) and the “correlation between Gleason Score and LWF then reinforces the idea that multi-echo T2 modelling shows promise as a method for detecting and grading PCa” (Discussion), Devine implies that the LWF values correlate with classifications of prostate cancer. Thus, the color-coded LWF map, which is generated as part of the multi-echo T2 modelling, provides a means of detecting scanner, albeit a simple method that may only be preliminary, but a method nonetheless.
Third, the independent claims except claim 16 merely recite determining “a tissue type”. The claims do not require “detecting and grading Prostate Cancer” (Remarks at pg. 9). Thus, even if the examiner’s understanding and interpretation of Devine is incorrect as to Devine disclosing a means of detecting prostate cancer, Devine still teaches determining a tissue type based on comparing LWF values to color-designated values for labeling an LWF map to distinguish areas of tissue likely being cancerous from those that are not.
At pages 9-10 of Remarks, Applicant argues that “there is nothing in Bydder that would lead the skilled person to modify Devine in an obvious way to use a fewer number of echoes.” Examiner respectfully disagrees. Devine already discloses that the aim of their work is produce accurate results using fewer echoes (Synopsis). Devine discloses reducing from 64 to 32 echoes leads to lower AUC, sensitivity and specificity. However, in the same breath, Devine notes that the disclosed modelling method “shows promise as a method for detecting and grading PCa”. Every design choice has tradeoffs. Fewer echoes may mean a drop in accuracy, for example, but would also mean a decrease in scan time, which is beneficial in cases where a patient may move during a scan. By reducing the number of echoes, Devine demonstrates that those of skill in the art before the invention was effectively filed were looking to reduce the number of echoes. Bydder is analogous art to Devine because both are concerned with multi-echo T2 modelling of MRI data and both are concerned with the same problem as the claimed invention, as Bydder discloses, “Considerable effort has been devoted to increasing the SNR in MRI and decreasing the scan time. However, trade-offs must be made between the SNR, the scan time, and also image quality” (Background). Thus, both Devine and Bydder establish that it is common knowledge to the skilled artisan to drive down the number of echoes. Bydder specifically discloses that as few as 8 or 12 echoes can be used. Being concerned with the same goal of reducing the number of echoes, it is reasonable that one of ordinary skill in the art being aware of both Devine and Bydder would have been motivated to modify Devine to use as few as 8 echoes to reduce scan time for a patient knowing that reducing the number of echoes comes with tradeoffs.
Applicant’s arguments, see Remarks at page 11, filed 22 August, 2025, with respect to the rejection of claims 4, 5, 8, and 12 under 25 U.S.C. 103 as being unpatentable over Devine in view of Bydder and in further view of Devine2 have been fully considered but are moot as they rely upon alleged deficiencies which the examiner has rebutted above.
Applicant’s arguments, see Remarks at page 11, filed 22 August, 2025, with respect to the rejection of claims 13 and 16 under 25 U.S.C. 103 as being unpatentable over Gong in view of Bydder have been fully considered but are moot as they rely upon alleged deficiencies which the examiner has rebutted above.
Examiner Note
This action includes two different sets of prior art rejections:
Set (1): Claims 1-3, 6, 7, 9, 14, 15, and 17 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gong; and claims 13 and 16 rejected under 35 U.S.C. 103 as being unpatentable over Gong in view of Bydder.
Set (2): Claims 1-3, 6, 7, 9-11, and 13-17 rejected under 35 U.S.C. 103 as being unpatentable over Devine in view of Bydder; and claims 4, 5, 8, and 12 rejected under 35 U.S.C. 103 as being unpatentable over Devine in view of Bydder as applied to claims 1-3, 6, 7, 9-11, and 13-17 above, and in further view of Devine2.
The second set of prior art rejections is provided because the first set relies on Gong, which was published within one year of the effective filing date of the instant application, but names two additional authors that are not listed as inventors of the instant application. Hence, the exceptions under 35 U.S.C. 102(b)(1) are presumed to not apply absent a declaration filed by Applicant.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 6, 7, 9, 14, 15, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Optimisation of Luminal Water Imaging for Classification of Prostate Cancer (Abstract #2371) (cited on IDS) to Gong et al. (published Apr. 26, 2019 and names additional authors Francesco Giganti and Edward Johnston) (hereinafter “Gong”).
Regarding claim 1, Gong teaches an image processing method comprising:
receiving MRI data representing a scan of an organ of a patient (Method, “Following informed consent, 19 men (mean age 66 years) were imaged on a 3.0T Phillips Achieva system using a 32-channel cardiac coil.”), the MRI data including multiecho data for a plurality of pixels (Synopsis, “multi-echo T2 sequence”);
for each of a plurality of pixels of the MRI data:
fitting the multiecho data to a simulated decay curve (Figure 3, “curve fitting”);
calculating a tissue index based on at least one parameter of the simulated decay curve (Method, “Luminal Water Fraction (LWF) maps were generated for each patient from the acquired 32 echo dataset”); and
comparing the tissue index to a threshold to determine a tissue type (Method, “differentiation between cancer and benign ROls”; By comparing the LWF values of all different numbers of echoes to each other for both cancerous and benign T2 distributions through the data generated and presented in Figures 2 and 3, Gong discloses comparing the benign LWF values (i.e., tissue index) to cancerous LWF values (that serve as thresholds to differentiate the tissue type being cancer as opposed to being cancerous or not benign) and comparing the cancerous LWF values (i.e., tissue index) to benign LWF values (that serve as thresholds indicative of the tissue type being benign or not cancerous).), wherein each pixel of the multiecho data consists of 16 or fewer echoes (Method, “ROls were transferred to the LWF maps and ROC analysis performed to evaluate classification accuracy of LWF (for differentiation between cancer and benign ROls) derived from each map (32, 16, 8 and 6 echo).”).
Regarding claim 2, Gong teaches a method according to claim 1 wherein each pixel of the multiecho data consists of 8 or fewer echoes, desirably 6 or fewer echoes (Method, “ROls were transferred to the LWF maps and ROC analysis performed to evaluate classification accuracy of LWF (for differentiation between cancer and benign ROls) derived from each map (32, 16, 8 and 6 echo).”).
Regarding claim 3, Gong teaches a method according to claim 1 wherein the at least one parameter is selected from the group consisting of:
area under long T2 distribution (AL) (pg. 3, “Corresponding T2 distributions (left column) with calculated … Tlong peak area (A2) used to derive luminal water fraction (LWF).”), area under short T2 distribution (AS) (pg. 3, “Corresponding T2 distributions (left column) with calculated Tshort peak area (A1) … used to derive luminal water fraction (LWF).”), Tshort (pg. 3, “Tshort peak area (A1)”), Tlong (pg. 3, “Tlong peak area (A2)”), and the magnitude ratio between the long and short peaks (α).
Regarding claim 6, Gong teaches a method according to claim 1 wherein comparing the tissue index to a threshold comprises determining that a pixel likely corresponds to abnormal tissue if the tissue index is below a lower threshold and determining that a pixel likely corresponds to normal tissue if the tissue index is above an upper threshold (LWF/LWI distinguishes benign from cancerous tissue, thereby acting as a threshold).
Regarding claim 7, Gong teaches a method according to claim 1 wherein comparing the tissue index to a threshold comprises comparing the tissue index corresponding to a first part of the organ to a first threshold and comparing the tissue index corresponding to a second part of the organ to a second threshold (LWF/LWI distinguishes benign from cancerous tissue, thereby acting as a threshold).
Regarding claim 9, Gong teaches a method according to claim 1 wherein the MRI data is a T2 sequence (Synopsis, “multi-echo T2 sequence”).
Claims 14 and 15 substantially correspond to claims 1 and 2 by reciting a method of imaging comprising the same steps as recited in claims 1 and 2 and the additional step: performing a magnetic resonance imaging process to obtain multiecho MRI data corresponding to a scan of an organ of a patient (Gong, Method, “Following informed consent, 19 men (mean age 66 years) were imaged on a 3.0T Phillips Achieva system using a 32-channel cardiac coil.”).
Regarding claim 17, Gong teaches the method of claim 14 wherein the organ is selected from the group consisting of: prostate (Method, “prostate”), pancreas, breast, and a glandular organ.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 6, 7, 9-11, and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Two Compartment fitting for Luminal Water Imaging: Multi-Echo T2 in Prostate Cancer to Devine et al. (hereinafter “Devine”) in view of U.S. Pat. No. 7,795,869 to Bydder (hereinafter “Bydder”).
Regarding claim 1, Devine teaches an image processing method comprising:
receiving MRI data (Devine, pg. 1, “multi-echo T2 modelling”; multi-echo T2 weighted imaging is an MRI imaging method) representing a scan of an organ of a patient (Devine, pg. 1, “detecting and grading Prostate Cancer”; pg. 1, “19 subjects were imaged for this study”), the MRI data including multiecho data for a plurality of pixels (digital images are made of pixels);
for each of a plurality of pixels of the MRI data:
fitting the multiecho data to a simulated decay curve (Devine, pg. 1, “For each iteration the original and new fitting methods were tested using 64-echo and 32-echo simulation signals respectively. The mean LWF across the 50 iterations was then calculated for both models in order to show how the two compare over a range of LWF and SNR values.”);
calculating a tissue index (LWF) based on at least one parameter of the simulated decay curve (Devine, pg. 1, “The LWF was calculated as the area under the long T2 component divided by the area under both components.”; The luminal water fraction (LWF) is used to differentiate benign tissue from cancerous tissue.); and
comparing the tissue index to a threshold to determine a tissue type (Devine, pg. 3, Figure 4, “LWF map of the prostate. Note the higher LWF in the peripheral zone (PZ), consistent with histological findings of large regular acini and loosely woven stroma in the PZ5”; The LWF map provides a means of “detecting and grading Prostate Cancer” (Synopsis). The LWF map includes ten threshold values ranging between 0 and 1 in increments of .1.), but does not teach that which is explicitly taught by Bydder.
Bydder teaches wherein each pixel of the multiecho data consists of 16 or fewer echoes (Bydder, col. 3, ll. 53-54, “FIGS. 14A, 14B and 14C show test results of T2-decay fitting in multi-echo data sets.”; col. 10, ll. 42-26, “In tests with the Siemens Symphony Quantum 1.5T scanner, data sets were acquired on using multi-echo spin-echo (TR 500, TE 12, 24, 36, ... ) and gradient echo (TR 100, TE 2.2, 3.0, 3.8, ... ) sequences with up to 16 echoes.”; col. 12, ll. 39-41, “FIGS. 12A-12C show results from adaptive filtering on complex images from a SENSE 3x accelerated SPGR acquisition with 8 echoes.”).
Devine discloses a method of multi-echo T2 modelling of MRI data using 32 echoes in comparison using 64 echoes. Thus, Devine shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes. Bydder discloses a method of multi-echo T2 modelling of MRI data using up to 16 echoes and as few as 8 echoes. Thus, Bydder shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes.
A person of ordinary skill in the art would have been motivated to use the multi-echo T2 modelling method disclosed by Devine with fewer than 16 echoes, including 8 echoes, as disclosed by Bydder, to thereby configure the MRI scanning parameters to use fewer echoes instead of the 32 echoes disclosed by Devine. Based on the foregoing, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made such modification according to known methods to yield the predictable results to have the benefit of reducing scan time and/or improving SNR.
Regarding claim 2, Devine in view of Bydder teaches a method according to claim 1 wherein each pixel of the multiecho data consists of 8 or fewer echoes (Bydder, col. 12, ll. 39-41, “FIGS. 12A-12C show results from adaptive filtering on complex images from a SENSE 3x accelerated SPGR acquisition with 8 echoes.”), desirably 6 or fewer echoes (Bydder, col. 12, ll. 39-41, “FIGS. 12A-12C show results from adaptive filtering on complex images from a SENSE 3x accelerated SPGR acquisition with 8 echoes.”).
The rationale for obviousness is the same as provided for claim 1.
Regarding claim 3, Devine in view of Bydder teaches a method according to claim 1 wherein the at least one parameter is selected from the group consisting of:
area under long T2 distribution (AL) (Devine, pg. 1, “The LWF was calculated as the area under the long T2 component divided by the area under both components”), area under short T2 distribution (AS), Tshort (Devine, pg. 1, “mean and standard deviation of the short T2 peak (μ1 and σ1)”), Tlong (Devine, pg. 1, “The LWF was calculated as the area under the long T2 component divided by the area under both components”), and the magnitude ratio between the long and short peaks (α) (Devine, pg. 1, “relative fraction between the two compartments (α)”).
Regarding claim 6, Devine in view of Bydder teaches method according to claim 1 wherein comparing the tissue index to a threshold comprises determining that a pixel likely corresponds to abnormal tissue if the tissue index is below a lower threshold (Devine, Figure, 4; 0.9 is a lower threshold relative to 1.0. An LWF of 0.8 is more abnormal than an LWF of, for example, 0.2.) and determining that a pixel likely corresponds to normal tissue if the tissue index is above an upper threshold (Devine, Figure, 4; 0.1 is an upper threshold relative to 0.0. An LWF of 0.2 corresponds more to normal tissue than an LWF of, for example, 0.8, where the higher LWF is “consistent with histological findings”.).
Regarding claim 7, Devine in view of Bydder teaches method according to claim 1 wherein comparing the tissue index to a threshold comprises comparing the tissue index corresponding to a first part of the organ to a first threshold and comparing the tissue index corresponding to a second part of the organ to a second threshold (Devine, pg. 1, “Using a Spearman’s rank correlation test a correlation of -0.667 was found between Gleason Score and LWF in 31 ROIs. Figure 3 shows the AUC, sensitivity and specificity achieved by the new fitting method in 31 ROIs. Figure 4 is an example LWF map of the prostate.”; Different ROIs correspond to different parts of the prostate. Each ROI is compared to the various thresholds described above. The LWF maps show comparisons of tissue by presenting them side-by-side overlaid with colored annotations.).
Regarding claim 9, Devine in view of Bydder teaches a method according to claim 1 wherein the MRI data is a T2 sequence (Devine, Synopsis, “multi-echo T2 modelling”).
Regarding claim 10, Devine in view of Bydder teaches a method according to claim 9 wherein fitting the multiecho data comprises fitting the multiecho data to a combination of a fast Gaussian distribution and a slow Gaussian distribution (Devine, pg. 1, “The method proposed here constrains this distribution to consist of two Gaussians.”), the slow Gaussian distribution simulating a longer relaxation time than the fast Gaussian distribution (Devine, pg. 1, “Simulated signal decays were produced for two separate underlying T2 distributions (two delta functions at T2short and T2long and two Gaussian distributions with means T2short and T2long, fixed at T2short = 75ms and T2long = 600ms) with varying values of LWF, Signal-to-Noise Ratio (SNR) and Number of Echoes (NE).”; 600 ms is longer than 75 ms. T2 is the transverse relaxation time. Thus, 600 ms is a longer relaxation time than 75 ms.).
Regarding claim 11, Devine in view of Bydder teaches a method according to claim 10 wherein calculating a tissue index comprises calculating a tissue index based on the areas under the fast Gaussian distribution and the slow Gaussian distribution (Devine, pg. 1, “The method proposed here constrains this distribution to consist of two Gaussians.”).
Claim 13 substantially corresponds to claim 1 by reciting a non-transitory computer-readable storage medium comprising executable code configured to perform a method corresponding to the method of claim 1.
Devine in view of Bydder does not explicitly teach a non-transitory computer-readable storage medium.
However, Bydder further discloses a non-transitory computer-readable storage medium (Bydder, col. 14, ll. 6-15, “a machine-readable storage device”).
Devine and Bydder are analogous art to the claimed invention of claim 13 for the same reasons provided in the rejection of claim 1 under 35 U.S.C. 103.
A person of ordinary skill in the art would have been motivated to execute the multi-echo T2 modelling method disclosed by Devine in view of Bydder as stored computer program instructions as disclosed by Bydder, to thereby process MRI data and compute the LWF using a computer. Based on the foregoing, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made such modification according to known methods to yield the predictable results to have the benefit of placing the method in an easily reproducible and transferrable form that could be executed by any general-purpose processor of a computer.
Claims 14 and 15 substantially correspond to claims 1 and 2 by reciting a method of imaging comprising the same steps as recited in claims 1 and 2 and the additional step: performing a magnetic resonance imaging process to obtain multiecho MRI data corresponding to a scan of an organ of a patient (Devine, pg. 1, “In order to investigate the relationship between this new fitting method and Gleason Score, 19 subjects were imaged for this study. The scan parameters are included in Figure 1”).
Claims 14 and 15 are rejected for the same rationale for obviousness provided for claim 1.
Claim 16 substantially corresponds to claim 1 by reciting a non-transitory computer-readable storage medium comprising executable code configured to perform a method corresponding to the method of claim 1 and additionally reciting optionally 8 or fewer echoes, optionally 6 or fewer echoes.
Devine in view of Bydder does not explicitly teach a non-transitory computer-readable storage medium.
However, Bydder further discloses a non-transitory computer-readable storage medium (Bydder, col. 14, ll. 6-15, “machine-readable storage device”)
The rationale for obviousness is the same as provided for claim 13.
Regarding claim 17, Devine in view of Bydder teaches the method of claim 14 wherein the organ is selected from the group consisting of: prostate (Devine, Synopsis, “detecting and grading Prostate Cancer”), pancreas, breast, and a glandular organ.
Claims 4, 5, 8, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Devine in view of Bydder as applied to claims 1-3, 6, 7, 9-11, and 13-17 above, and in further view of Simplified Luminal Water Imaging for the Detection of Prostate cancer From Multiecho T2 MR Images (cited on IDS) to Devine et al. (hereinafter “Devine2”).
Regarding claim 4, Devine in view of Bydder teaches a method according to claim 3, but does not teach that which is explicitly taught by Devine2.
Devine2 teaches wherein calculating the tissue index comprises dividing the area under long T2 distribution (AL) of the simulated decay curve by the sum of the area under long T2 distribution (AL) and area under short T2 distribution (AS) of the simulated decay curve (Devine2, pg. 913, “The areas under the individual peaks, A1 for the shorter T2 peak and A2 for the longer T2 peak, were calculated by integrating the respective Gaussians using their magnitude, mean, and variance. The LWF was then calculated as the fraction of the total area under the distribution curve attributed to the peak with the longer T2: LWF = A2/(A1 + A2)”).
Devine discloses a method of multi-echo T2 modelling of MRI data using 32 echoes compared to using 64 echoes. Thus, Devine shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes. Bydder discloses a method of multi-echo T2 modelling of MRI data using up to 16 echoes and as few as 8 echoes. Thus, Bydder shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes. Devine2 discloses using 32 echoes and 64 echoes (Devine2, pg. 913, Table 1) and processing multi-echo T2 sequences to calculate LWF (Devine2, pg. 913). Thus, Devine2 shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes.
A person of ordinary skill in the art would have been motivated to combine the multi-echo T2 modelling method disclosed by Devine in view of Bydder with the LWF equation disclosed by Devine2, to thereby calculate the LWF using MRI data obtained with fewer echoes than as disclosed by Devine and with the LWF equation disclosed by Devine2. Based on the foregoing, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made such modification according to known methods to yield the predictable results to have the benefit of provides values “that are in close agreement with those of the original LWI” (Devine, Introduction section) using fewer echoes.
Regarding claim 5, Devine in view of Bydder and in further view of Devine2 teaches a method according to claim 4 wherein the threshold is in the range of 0.05 to 0.15 (Devine, Figure 4 includes a threshold value of 0.1, which is between 0.05 and 0.15).
Regarding claim 8, Devine in view of Bydder teaches a method according to claim 1 wherein the fitting comprises determining a contour of an organ in the MRI data (Devine, Synopsis, “19 patients were imaged and the images were contoured in both cancerous and benign regions”), but does not teach that which is explicitly taught by Devine2.
Devine2 teaches determining median values of the multiecho data over the area of the organ (Devine2, pg. 912, “a two-Gaussian model was fitted to the individual T 2 signal decay curves using a least-squares regression.”); and setting the median values as initial parameters of a regression method (Devine2, pgs. 913-14, “Differences were characterized between the median parameter values of ROIs with different PI-RADS v2 groupings of scores and determined using a logistic regression model combined with 5-fold crossvalidation”; pg. 914, “The mean values for sensitivity, specificity, and area-under-curve (AUC) values across the five-folds were also computed using a receiver operating characteristic (ROC) analysis. Sensitivity and specificity values were calculated from the ROC analysis using an operating point with the shortest distance to the point of perfect discrimination. A logistic regression was performed on the median values of those ROIs with a corresponding histological grading in order to discern malignant (Gleason 3 + 3 and above) from nonmalignant tissue.”).
Devine, Bydder, and Devine2 are analogous art to the claimed invention of claim 8 for the same reasons provided in the rejection of claim 4 under 35 U.S.C. 103.
A person of ordinary skill in the art would have been motivated to combine the multi-echo T2 modelling method disclosed by Devine in view of Bydder with the logistic regression model disclosed by Devine2, to thereby set median values of the multiecho data as initial parameters. Based on the foregoing, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made such modification according to known methods to yield the predictable results to have the benefit of accurately discerning malignant from nonmalignant tissues, as suggested by Devine2.
Regarding claim 12, Devine in view of Bydder teaches a method according to claim 11, but does not teach that which is explicitly taught by Devine2.
Devine2 teaches wherein calculating a tissue index comprises calculating a tissue index based on the area under a peak of the slow Gaussian distribution divided by the sum of the areas under a peak of the fast Gaussian distribution and the peak of the slow Gaussian distribution (Devine2, pg. 913, “The areas under the individual peaks, A1 for the shorter T2 peak and A2 for the longer T2 peak, were calculated by integrating the respective Gaussians using their magnitude, mean, and variance. The LWF was then calculated as the fraction of the total area under the distribution curve attributed to the peak with the longer T2: LWF = A2/(A1 + A2)”).
The rationale for obviousness is the same as provided for claim 4.
Claims 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Gong in view of Bydder.
Claim 13 substantially corresponds to claim 1 by reciting a nontransitory computer-readable storage medium comprising executable code configured to perform a method corresponding to the method of claim 1.
Gong does not explicitly teach a nontransitory computer-readable storage medium.
Bydder discloses a nontransitory computer-readable storage medium (Bydder, col. 14, ll. 6-15, “machine-readable storage device”).
Gong discloses a method of multi-echo T2 modelling of MRI data using fewer echoes compared to using 64 echoes (Synopsis). Thus, Gong shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes. Bydder discloses a method of multi-echo T2 modelling of MRI data using up to 16 echoes and as few as 8 echoes. Thus, Bydder shows that it was known in the art before the effective filing date of the claimed invention to minimize the number of echoes, which is analogous to the claimed invention in that it is pertinent to the problem being solved by the claimed invention, processing MRI image data using fewer echoes.
A person of ordinary skill in the art would have been motivated to execute the multi-echo T2 modelling method disclosed by Gong as stored computer program instructions as disclosed by Bydder, to thereby process MRI data and compute the LWF using a computer. Based on the foregoing, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made such modification according to known methods to yield the predictable results to have the benefit of placing the method in an easily reproducible and transferrable form that could be executed by any general-purpose processor of a computer.
Claim 16 substantially corresponds to claim 1 by reciting a nontransitory computer-readable storage medium comprising executable code configured to perform a method corresponding to the method of claim 1. Claim 16 is rejected for the same reasons as claim 1.
Gong does not explicitly teach a nontransitory computer-readable storage medium.
Bydder discloses a nontransitory computer-readable storage medium (Bydder, col. 14, ll. 6-15, “machine-readable storage device”).
The rationale for obviousness is the same as provided for claim 13 as rejected by Gong in view of Bydder.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RYAN P POTTS whose telephone number is (571)272-6351. The examiner can normally be reached M-F, 9am-5pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sumati Lefkowitz can be reached at 571-272-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RYAN P POTTS/Examiner, Art Unit 2672
/SUMATI LEFKOWITZ/Supervisory Patent Examiner, Art Unit 2672
1 https://web.archive.org/web/20191207173949/https://www.foxchase.org/blog/prostate-cancer-gleason-score-explained