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 Amendment
This office action is in response to the remarks filed on 03/20/2025.
The 35 USC § 112(b) rejection of claims 27-28 and 34 on the non-final dated 12/23/2024 have been withdrawn in light of claim amendments.
The amendment filed 03/20/2025 has been entered. Claims 1, 6-7, 9-12, 24, 26-37 are pending in the application. Claims 2-5, 8, 13-23, 25, have been canceled. Claims 36-37 have been newly added.
Drawings
The drawings are objected to because:
Fig. 7 does not contain units or scales on the X and Y axis
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6-7, 9-12, 24, 26-37 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite as it is unclear how for the following reasons:
Regarding the limitation “obtaining a reference input function relating to the subject, the reference input function reflecting a predicted concentration change of the tracer in the subject during at least a portion of the period other than the scan period in the examination period, and the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject”, it is unclear how the reference function is simultaneously dependent on the subject (“the reference input function reflecting a predicted concentration change of the tracer in the subject…”) as well as information that is independent of the subject (“the reference input function being a population-based input function that is determined based …. to a plurality of sample subjects other than the subject”. Clarification is needed. For examination purposes, this claim limitation will be interpreted as the reference input function being reflecting the a predicted concentration change of the tracer in the subject.
Claim 1 further recites “the examination period includes the scan period and a period other than the scan period”. This limitation is indefinite as it is unclear how there is a scan period other than a scan period, but the claim defines the scan period as “the scan period starts at a time point tb1 and ends at a time point tb3, tb
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being a time point when a concentration of the tracer in the subject is in a declining stage, tb1 being between tbo and tb2, tb3 being after tb2”. Clarification is needed. This claim will be interpreted as examination period includes multiple time points.
Claim 6 recites “wherein the generating a parametric image based on the input function and the at least one PET image…” in lines 1-2. This has unclear antecedent basis. Examiner suggests amending claim to recite “wherein the generating [[a]] the parametric image based on the input function and the at least one PET image”, if this is the same parametric image as recited in claim 1.
Claims 7 and 9-11 are rejected due to dependency on claim 1.
Claim 12 recites the following input function:
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This claim is indefinite as it is unclear what input function is used at time points tb1 and tb2, as both functions include the operator which “includes” the value at that time point (“≤” or “≥”), and is currently written as if both input functions are calculated at time points tb1 and tb2. Clarification is needed. Examiner suggests amending claim to change one of the symbols (“≤” or “≥”) to “<” or “>” associated with tb1 and tb2, to clarify that one equation is used at each time point tb1 and tb2. Furthermore, it is unclear what the “candidate input function” and the “reference input functions” are.
For examination purposes, this limitation will be interpreted as using multiple inputs to calculate the input function.
Claim 24 recites the terms “a second candidate input function”, “a concentration change”, “a period after the time point tbo”, and “a ratio”. These claims are indefinite as it unclear if these are the same “a second candidate input function”, “a concentration change”, “a period after the time point tbo”, and “a ratio”, as recited in claim 12, or different. Examiner suggests amending claim to recite “, wherein the determining [[a]] the second candidate input function that reflects [[a]] the concentration change of the tracer in the subject during [[a] ]the period after the time point tbo based on the first candidate input function and [[a]] the ratio of the first portion to the second portion, comprises: determining the ratio of the first portion to the second portion; and determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion”.
Claim 26 “wherein the generating a parametric image…” in lines 1-2. This claim is indefinite as it is unclear if this is the same “parametric image” as recited in claim 12, or is a different parametric image. Examiner suggests amending claim to recite “wherein the generating [[a]] of the parametric image…”
Claim 31 is indefinite for the following reasons:
It is unclear what the “K1” denotes in the equation (capital K)
It is unclear what each of the “functions” of the are in the equation (the input function and the relationship function).
It is unclear what the compartments in the functions are. In other words do the functions relate to a temporal or physical compartment.
It is unclear what the boundary conditions are for the integral.
Clarification is needed. For examination purposes, this claim will be interpreted as incorporating compartments into the input equation.
Claim 33 recites “wherein the determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period after the time point tbo based on the first candidate input function and a ratio of the first portion to the second portion…” in lines 1-4. This claim is indefinite as it is unclear whether “wherein the determining a second candidate input function that reflects a concentration change of the tracer” is the same as recited in claim 1, or is a different concentration. Examiner suggests amending claim to recite “wherein the determining [[a]] the second candidate input function that reflects [[a]] the concentration change of the tracer in the subject during a period after the time point tbo based on the first candidate input function and [[a]] the ratio of the first portion to the second portion”.
Claim 37 recites the following input function:
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This claim is indefinite as it is unclear what input function is used at time points tb1 and tb2, as both functions include the operator which “includes” the value at that time point (“≤” or “≥”), and is currently written as if both input functions are calculated at time points tb1 and tb2. Clarification is needed. Examiner suggests amending claim to change one of the symbols (“≤” or “≥”) to “<” or “>” associated with tb1 and tb2, to clarify that one equation is used at each time point tb1 and tb2. Furthermore, it is unclear what the “candidate input function” and the “reference input functions” are. For examination purposes, this limitation will be interpreted as calculating multiple input functions at different time points.
Claims 27-30 and 32 are rejected due to dependency on claim 12.
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.
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, 6-7, 9-10,12, 24, 26-37 are rejected under 35 U.S.C. 103 as being unpatentable over Kadrmas et al (US 20080230703 A1) in view of Leahy (US 20150363948 A1), and Uber (US 20140119621 A1).
Regarding claim 1, Kadrmas teaches a method implemented on a computing device (computing device [0011]) having at least one processor (processor [0043]) and at least one storage device (storage medium [0039]), the method comprising:
obtaining one positron emission tomography (PET) image of a subject (static image in PET [0085]) by performing a dual injection scan on the subject (single tracer injected repeatedly in a multiple-timepoint/dynamic scanning disclosed in [0049]), wherein the PET image is generated based on PET data acquired during a scan period in an examination period (static image in PET [0085]), the examination period includes the scan period and a period other than the scan period, a first portion of a tracer is injected into the subject at a time point tbo and a second portion of the tracer is injected into the subject at a time point tb2 after the time point tbo, and a PET scan is performed during the scan period, the scan period starts at a time point tb1 and ends at a time point tb3, tb1 being a time point when a concentration of the tracer in the subject is in a declining stage, tb1 being between tbo and tb2, tb3 being after tb2 (multiple PET tracers, a single tracer injected repeatedly, or a combination of tracers using multiple-timepoint or dynamic scanning, where the tracer administrations are simultaneous or staggered in time such that some or all of the PET timeframes, images, data, and/or datasets contain overlapping signals from more than one of the tracer administration [0049]; obtaining multi-tracer PET data of the subject by performing a PET scan of the subject substantially concurrently or subsequent to introducing the first tracer and continuing at least a portion of the time after the introduction of the at least second tracer into the subject, claim 1; [0093] discloses separate scans to be acquired during the scan period. As the scanning can begin after/subsequent to the first injection, and there can be multiple-points within the scanning there are at least three time points, one of which occurs prior to the first scan when the first tracer is injected, declining stage shown in fig. 11 below)
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Snippet of fig. 11 reproduced above with annotations
obtaining a reference input function relating to the subject, the reference input function reflecting a predicted concentration change of the tracer in the subject during at least a portion of the period other than the scan period in the examination period ([0136] and [0058] disclose predicted activity/distribution of the tracer) ;
determining, based on the at least one PET image and the reference input function, an input function that reflects a concentration change of the tracer in the subject during the examination period by ([0058] and [0060]-[0061] discloses input function using PET image data and the concentration change of the tracer) :
determining, based on the PET image ([0060]-[0061] discloses input function using PET image data), a first candidate input function that reflects a concentration change of the tracer in the subject during the scan period from tb1 to tb3 ([0102] discloses calculation of separate input functions calculated from the image data acquired from the different time points):
determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tb0 to a time point tb4 based on the first candidate input function, the first portion, and the second portion, tb4 being between tb0 and time point tb1 ([0096]-[0097] and [0102]-[0103] discloses calculation of multiple input functions using dual-injection data obtained from the PET image data, including data that was collected from different time frames and staggered injections, as shown in fig. 11 below) and
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Fig. 11 of Kadrmas reproduced above
Kadrmas, however, does not teach: the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject;
[determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function] and a ratio of the first portion to the second portion
modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions;
and generating a parametric image based on the input function and the PET image, wherein the parametric image reflects a kinetic parameter of the tracer in the subject.
Leahy is considered analogous to the instant application as “Direct Patlak Estimation from List-Mode PET Data” is disclosed (title).
Leahy teaches:
the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject ([0043] and [0060]-[0061] discloses use of a population-based input function from a group/plurality of subjects)
generating a parametric image based on the input function (blood input function C(t) [0047]) and the PET image (The data processing system may: reconstruct Patlak slope and intercept images of the subject … optimizing a penalized likelihood function using the list-mode PET data from at least two scans of the subject at each of the multiple bed positions; and store the reconstructed image in a storage device or displays the reconstructed image on a display system [0020]), wherein the parametric image reflects a kinetic parameter of the tracer in the subject (reconstruction of parametric whole or extended body PET images are now described, … from list-mode PET data using a Patlak model to represent tracer dynamics [0040]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kadrmas to include the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject and generating a parametric image based on the input function and the PET image, wherein the parametric image reflects a kinetic parameter of the tracer in the subject, as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
The combined invention still does not teach:
[determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function] and a ratio of the first portion to the second portion
modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions).
Uber, however, teaches:
determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function (the input function may be determined two or more times throughout a procedure [0022]; The analyzer uses the data from the imaging system 110 to first determine the input function [0075]) and a ratio of the first portion to the second portion (For example, the system 10 may allow the user to program the injector 140 to inject a tracer 141 at a certain rate … The system 10 may also allow the user to program the injector 140 to inject several discrete doses of tracer over a period of time, for example, one 10 ml injection every 5 minutes or 10 minutes for 30 minutes or 40 minutes… a certain dose of tracer 141 may be administered when the input function reaches a particular lower threshold, [0048]; FIG. 4 a shows the general timeline of the procedure [0078]; FIG. 4 c illustrates in detail how the injector could be programmed to accomplish this protocol [0079] figs. 4A and 4C, reproduced below, show the time and amount of concentration delivered at each time point, these can be used to determine ratios, the maximum blood concentration, which is used for the input function calculation, is calculated after each administration of the tracer).
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Figs. 4A of Uber reproduced above
modifying the reference input function ([0029]-[0031], [0052], [0063], disclose adjusting the reference input function variables based off multiple factors including circulation delay, different model factors), wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1 (the input function may be determined two or more times throughout a procedure. In certain embodiments, the imaging data collected from the sample tissue can be normalized based on multiple input functions determined throughout the procedure [0022]; normalizing the based off multiple input functions would inherently match up time points); and
generating the input function by combining the modified reference input function and the first and second candidate input functions (determining an input function from an organ or other part of a patient's body having a high blood volume and, in some embodiments, the input function may be determined two or more times throughout a procedure… the imaging data collected from the sample tissue can be normalized based on multiple input functions determined throughout the procedure [0022]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function and a ratio of the first portion to the second portion, and modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 6, modified Kadrmas teaches the method of claim 1, as discussed above. Kadrmas, however does not teach, wherein the generating a parametric image based on the input function and the at least one PET image comprises: generating a relationship function between a compartment model, the input function, and the at least one PET image, the compartment model being used to model tracer dynamics within the subject; and generating the parametric image based on the relationship function according to the non-linear parametric estimation algorithm.
Leahy, however teaches:
wherein the generating a parametric image (reconstruction of parametric whole or extended body PET images [0040]) based on the input function and the at least one PET image (The blood input function required for the Patlak model may be estimated from the image data in combination with a population based average input function [0043]) comprises:
generating a relationship function (tracer time activity curve (TAC) [0047]; the tracer time activity curve is the relationship function as claimed) between a compartment model (two compartment kinetic model [0047]) , the input function (blood input function C(t) [0047]), and the at least one PET image (blood input function required for the Patlak model may be estimated from the image data [0043]), the compartment model being used to model tracer dynamics within the subject (PET data may be continuously collected from the time the tracer is administered and then fit to a kinetic model that represents dynamic behavior through transfer between a series of compartments [0012])
and generating the parametric image (reconstruction of parametric whole or extended body PET images are now described, … from list-mode PET data using a Patlak model to represent tracer dynamics [0040]) based on the relationship function (The data processing system may: reconstruct Patlak slope and intercept images of the subject … optimizing a penalized likelihood function using the list-mode PET data from at least two scans of the subject at each of the multiple bed positions; and store the reconstructed image in a storage device or displays the reconstructed image on a display system [0020]) according to a non-linear parametric estimation algorithm (A penalized maximum likelihood numerical optimization method may be used to reconstruct the images [0042]; the non-linear parametric estimation algorithm is the maximum likelihood estimation algorithm in light of claim 9).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include the generating a parametric image based on the input function and the at least one PET image comprises: generating a relationship function between a compartment model, the input function, and the at least one PET image, the compartment model being used to model tracer dynamics within the subject; and generating the parametric image based on the relationship function according to a non-linear parametric estimation algorithm, as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
Regarding claim 7, modified Kadrmas teaches the method of claim 6, as discussed above. Kadrmas further teaches wherein the compartment model is used to model at least one of: a forward transport of the tracer from the plasma of the subject to the tissue ([0134]-[0135] discloses a compartment model for the tracer concentration through extravascular tissue) of the subject, a backward transport of the tracer from the plasma to the tissue, a phosphorylation process in the tissue of the subject, or a dephosphorylation process in the tissue of the subject.
Regarding claim 9, modified Kadrmas teaches the method of claim 6, as discussed above. Kadrmas, however, does not teach the non-linear parametric estimation algorithm includes a maximum likelihood estimation (MLE) algorithm. Leahy, however, teaches wherein the non-linear parametric estimation algorithm includes a maximum likelihood estimation (MLE) algorithm (A penalized maximum likelihood numerical optimization method may be used to reconstruct the images [0042]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include the non-linear parametric estimation algorithm includes a maximum likelihood estimation (MLE) algorithm, as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
Regarding claim 10, modified Kadrmas teaches the method of claim 1, as discussed above. Kadrmas further teaches wherein the tracer is an 18F-fluorodeoxyglucose (FDG) (one or more of the tracers used for cancer imaging comprise FDG [0145]).
Regarding claim 12, Kadrmas teaches a system, comprising:
at least one storage device (storage medium [0039]), storing executable instructions (computer-readable program instructions [0039]),
and at least one processor in communication (processor [0043]) with the at least one storage device (storage medium [0039]), wherein when executing the executable instructions (computer-readable program instructions [0039]), the at least one processor causes the system to perform operations including:
obtaining one positron emission tomography (PET) image of a subject (static image in PET [0085]) by performing a dual injection scan on the subject (single tracer injected repeatedly in a multiple-timepoint/dynamic scanning disclosed in [0049]), wherein the PET image is generated based on PET data acquired during a scan period in an examination period, period, a first portion of a tracer is injected into the subject at a time point tb0 and a second portion of the tracer is injected into the subject at a time point tb2 after the time point tb0, and a PET scan is performed during the scan period, the scan period starts at a time point tb1 and ends at a time point tb3, tb1 being a time point when a concentration of the tracer in the subject is in a declining stage, tb1 being between tb0 and t62,tb3 being after tb2 (multiple PET tracers, a single tracer injected repeatedly, or a combination of tracers using multiple-timepoint or dynamic scanning, where the tracer administrations are simultaneous or staggered in time such that some or all of the PET timeframes, images, data, and/or datasets contain overlapping signals from more than one of the tracer administration [0049]; obtaining multi-tracer PET data of the subject by performing a PET scan of the subject substantially concurrently or subsequent to introducing the first tracer and continuing at least a portion of the time after the introduction of the at least second tracer into the subject, claim 1; [0093] discloses separate scans to be acquired during the scan period. As the scanning can begin after/subsequent to the first injection, and there can be multiple-points within the scanning there are at least three time points, one of which occurs prior to the first scan when the first tracer is injected, declining stage shown in fig. 11 below);
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Snippet of fig. 11 reproduced above with annotations
obtaining a reference input function relating to the subject, the reference input function reflecting a predicted concentration change of the tracer in the subject during at least a portion of the period other than the scan period in the examination period ([0136] and [0058] disclose predicted activity/distribution of the tracer) ;
determining, based on the at least one PET image and the reference input function, an input function that reflects a concentration change of the tracer in the subject during the examination period by ([0058] and [0060]-[0061] discloses input function using PET image data and the concentration change of the tracer) by:
determining, based on the PET image([0060]-[0061] discloses input function using PET image data), a first candidate input function that reflects a concentration change of the tracer in the subject during the scan period from tb1 to tb3 ([0102] discloses calculation of separate input functions calculated from the image data acquired from the different time points):
determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tb0 to a time point tb4 based on the first candidate input function, the first portion, and the second portion, tb4 being between tb0 and time point tb1 ([0096]-[0097] and [0102]-[0103] discloses calculation of multiple input functions using dual-injection data obtained from the PET image data, including data that was collected from different time frames and staggered injections, as shown in fig. 11 below) and
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Fig. 11 of Kadrmas reproduced above
Kadrmas, however, does not teach:the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject;
[determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function] and a ratio of the first portion to the second portion
modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions;
and generating a parametric image based on the input function and the PET image, wherein the parametric image reflects a kinetic parameter of the tracer in the subject, wherein the input function is presented according to the following Equation:
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where t denotes a time point in the examination period; C,(t) denotes a value of the input function at the time point t; Cimage(t) denotes a value of one of the candidate input functions at the time point t; Cp0(t) denotes the reference input function; and y and µ denote scaling constants to satisfy µ Cp0(tb4)=Cimage(tb3), and
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.
Leahy is considered analogous to the instant application as “Direct Patlak Estimation from List-Mode PET Data” is disclosed (title).
Leahy teaches:
the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject ([0043] and [0060]-[0061] discloses use of a population-based input function from a group/plurality of subjects)
generating a parametric image based on the input function (blood input function C(t) [0047]) and the PET image (The data processing system may: reconstruct Patlak slope and intercept images of the subject … optimizing a penalized likelihood function using the list-mode PET data from at least two scans of the subject at each of the multiple bed positions; and store the reconstructed image in a storage device or displays the reconstructed image on a display system [0020]), wherein the parametric image reflects a kinetic parameter of the tracer in the subject (reconstruction of parametric whole or extended body PET images are now described, … from list-mode PET data using a Patlak model to represent tracer dynamics [0040]), and wherein the input function is presented according to the following Equation:
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where t denotes a time point in the examination period; C,(t) denotes a value of the input function at the time point t; Cimage(t) denotes a value of one of the candidate input functions at the time point t; Cp0(t) denotes the reference input function; and y and µ denote scaling constants to satisfy µ Cp0(tb4)=Cimage(tb3), and
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, ([0060]-[0062] discloses obtaining the input function using multiple constants/samples).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kadrmas to include the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject and generating a parametric image based on the input function and the PET image, wherein the parametric image reflects a kinetic parameter of the tracer in the subject, wherein the input function is presented according to the following Equation:
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where t denotes a time point in the examination period; C,(t) denotes a value of the input function at the time point t; Cimage(t) denotes a value of one of the candidate input functions at the time point t; Cp0(t) denotes the reference input function; and y and µ denote scaling constants to satisfy µ Cp0(tb4)=Cimage(tb3), and
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as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
The combined invention still does not teach:
[determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function] and a ratio of the first portion to the second portion
modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions).
Uber, however, teaches:
determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function ((the input function may be determined two or more times throughout a procedure [0022]; The analyzer uses the data from the imaging system 110 to first determine the input function [0075]) and a ratio of the first portion to the second portion (For example, the system 10 may allow the user to program the injector 140 to inject a tracer 141 at a certain rate … The system 10 may also allow the user to program the injector 140 to inject several discrete doses of tracer over a period of time, for example, one 10 ml injection every 5 minutes or 10 minutes for 30 minutes or 40 minutes… a certain dose of tracer 141 may be administered when the input function reaches a particular lower threshold, [0048]; FIG. 4 a shows the general timeline of the procedure [0078]; FIG. 4 c illustrates in detail how the injector could be programmed to accomplish this protocol [0079] figs. 4A and 4C, reproduced below, show the time and amount of concentration delivered at each time point, these can be used to determine ratios, the maximum blood concentration, which is used for the input function calculation, is calculated after each administration of the tracer).
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Figs. 4A of Uber reproduced above
modifying the reference input function ([0029]-[0031], [0052], [0063], disclose adjusting the reference input function variables based off multiple factors including circulation delay, different model factors), wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1 (the input function may be determined two or more times throughout a procedure. In certain embodiments, the imaging data collected from the sample tissue can be normalized based on multiple input functions determined throughout the procedure [0022]; normalizing the based off multiple input functions would inherently match up time points); and
generating the input function by combining the modified reference input function and the first and second candidate input functions (determining an input function from an organ or other part of a patient's body having a high blood volume and, in some embodiments, the input function may be determined two or more times throughout a procedure… the imaging data collected from the sample tissue can be normalized based on multiple input functions determined throughout the procedure [0022]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period from the time point tbo to a time point tb4 based on the first candidate input function and a ratio of the first portion to the second portion, and modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 24, modified Kadrmas teaches the system of claim 23, as discussed above. Kadrmas, however, does not teach wherein the determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period after the time point tb0 based on the first candidate input function and a ratio of the first portion to the second portion: determining the ratio of the first portion to the second portion; and determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion.
Uber is considered analogous to the instant application as “System and method for rapid quantitative dynamic molecular imaging scans” is disclosed (title).
Uber, however, teaches:
wherein the determining a second candidate input function (the input function may be determined two or more times throughout a procedure [0022]) that reflects a concentration change of the tracer in the subject during a period after the time point tb0 based on the first candidate input function and a ratio of the first portion to the second portion comprises (an “input function” that represents the concentration of a tracer in the blood plasma over time must be determined for the model [0025]) :
determining the ratio of the first portion to the second portion (For example, the system 10 may allow the user to program the injector 140 to inject a tracer 141 at a certain rate … The system 10 may also allow the user to program the injector 140 to inject several discrete doses of tracer over a period of time, for example, one 10 ml injection every 5 minutes or 10 minutes for 30 minutes or 40 minutes… a certain dose of tracer 141 may be administered when the input function reaches a particular lower threshold, [0048]; FIG. 4 a shows the general timeline of the procedure [0078]; FIG. 4 c illustrates in detail how the injector could be programmed to accomplish this protocol [0079] figs. 4A and 4C, reproduced below, show the time and amount of concentration delivered at each time point, these can be used to determine ratios, the maximum blood concentration, which is used for the input function calculation, is calculated after each administration of the tracer);
and determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion (the imaging data collected from the sample tissue can be normalized based on multiple input functions determined throughout the procedure [0022]).
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Figs. 4A of Uber reproduced above
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Fig. 4C of Uber reproduced above
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include determining the ratio of the first portion to the second portion; and determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion, as taught in Uber, in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 26, modified Kadrmas teaches system of claim 12, as discussed above. Kadrmas, however does not teach, wherein the generating a parametric image based on the input function and the at least one PET image comprises: generating a relationship function between a compartment model, the input function, and the at least one PET image, the compartment model being used to model tracer dynamics within the subject; and generating the parametric image based on the relationship function according to the non-linear parametric estimation algorithm.
Leahy, however teaches:
wherein the generating a parametric image (reconstruction of parametric whole or extended body PET images [0040]) based on the input function and the at least one PET image (The blood input function required for the Patlak model may be estimated from the image data in combination with a population based average input function [0043]) comprises:
generating a relationship function (tracer time activity curve (TAC) [0047]; the tracer time activity curve is the relationship function as claimed) between a compartment model (two compartment kinetic model [0047]) , the input function (blood input function C(t) [0047]), and the at least one PET image (blood input function required for the Patlak model may be estimated from the image data [0043]), the compartment model being used to model tracer dynamics within the subject (PET data may be continuously collected from the time the tracer is administered and then fit to a kinetic model that represents dynamic behavior through transfer between a series of compartments [0012])
and generating the parametric image (reconstruction of parametric whole or extended body PET images are now described, … from list-mode PET data using a Patlak model to represent tracer dynamics [0040]) based on the relationship function (The data processing system may: reconstruct Patlak slope and intercept images of the subject … optimizing a penalized likelihood function using the list-mode PET data from at least two scans of the subject at each of the multiple bed positions; and store the reconstructed image in a storage device or displays the reconstructed image on a display system [0020]) according to the non-linear parametric estimation algorithm (A penalized maximum likelihood numerical optimization method may be used to reconstruct the images [0042]; the non-linear parametric estimation algorithm is the maximum likelihood estimation algorithm in light of claim 9).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include the generating a parametric image based on the input function and the at least one PET image: generating a relationship function between a compartment model, the input function, and the at least one PET image, the compartment model being used to model tracer dynamics within the subject; and generating the parametric image based on the relationship function according to the non-linear parametric estimation algorithm, as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
Regarding claim 27, modified Kadrmas teaches the system of claim 24, as discussed above. Kadrmas further teaches wherein the shape of the second candidate input function is determined based on the first candidate input function and the ratio of the first portion to the second portion (fig. 11, snippet reproduced below, depicts a plot of tracer time activity curve of a staggered injection, both tracers have two shapes that are the same, and the shape of the function accounts for tracer decay from the two tracer injections; Fig. 11 [0023]; [0049] discloses that the a single tracer injected repeatedly, or a combination of tracers using multiple-timepoint or dynamic scanning, where the tracer administrations are simultaneous or staggered in time such that some or all of the PET timeframes, images, data, and/or datasets contain overlapping signals from more than one of the tracer administrations).
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Fig. 11 reproduced above
Regarding claim 28, modified Kadrmas teaches the system of claim 27, as discussed above. Kadrmas further teaches wherein the ratio of the first portion to the second portion is equal to one ([0049] discloses that the a single tracer injected repeatedly, or a combination of tracers using multiple-timepoint or dynamic scanning, where the tracer administrations are simultaneous or staggered in time such that some or all of the PET timeframes, images, data, and/or datasets contain overlapping signals from more than one of the tracer administrations, i.e. a staggered injection of the same tracer would result in a ratio of one ), the shape of the second candidate input function is the same as the shape of the first candidate input function (fig. 11, snippet reproduced below, depicts a plot of tracer time activity curve of a staggered injection, both tracers have two shapes that are the same, and the shape of the function accounts for tracer decay from the two tracer injections; Fig. 11 [0023]).
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Fig. 11 reproduced above
Regarding claim 29, modified Kadrmas teaches the system of claim 12, as discussed above. Kadrmas, however, does not teach wherein the reference input function starts from the time point tb4 and ending at the time point tb1, and the operations further include: determining a third candidate input function based on the first portion, the second portion, and the reference input function, the third candidate input function reflecting a concentration change of the tracer in the subject during a period after the scan period, the period starting from the time point tb3 and ending at a time point tb5.
Uber is considered analogous to the instant application as “System and method for rapid quantitative dynamic molecular imaging scans” is disclosed (title).
Uber teaches: wherein the reference input function starts from the time point tb4 and ending at the time point tb1, and the operations further include: determining a third candidate input function based on the first portion, the second portion, and the reference input function, the third candidate input function reflecting a concentration change of the tracer in the subject during a period after the scan period, the period starting from the time point tb3 and ending at a time point tb5 ([0029] discloses that at input function can be determined any number of times throughout a procedure and while determining the maximum blood concentrations; analyze changes in radiotracer uptake over time using two or more passes through a scanner [0019]; Patlak model to represent tracer dynamics [0040]; the reference input function is the initial input function after first measuring the maximum blood concentration, and the plurality of candidate input functions are the measurements that are taken afterwards).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include wherein the reference input function starts from the time point tb4 and ending at the time point tb1, and the operations further include: determining a third candidate input function based on the first portion, the second portion, and the reference input function, the third candidate input function reflecting a concentration change of the tracer in the subject during a period after the scan period, the period starting from the time point tb3 and ending at a time point tb5, as taught in Uber, in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 30, modified Kadrmas teaches the system of claim 29, as discussed above. Kadrmas, however does not teach wherein the third candidate input function is determined by: generating a scaled reference input function by scaling the reference input function or a portion of the reference input function corresponding to a period after tb1 having the same duration as the period tb3 to tb5; and translating the scaled reference input function to generate the third candidate input function.
Uber, however, teaches wherein the third candidate input function is determined by: generating a scaled reference input function by scaling the reference input function or a portion of the reference input function corresponding to a period after tb1 having the same duration as the period tb3 to tb5 (used in analyzing the images acquired during the procedure [0053]; For example, in some embodiments, a radiopharmaceutical may be administered to a patient and a first sample may be obtained from the patient a first time period after administration. A second sample may be obtained after a second time period after administration, and the emission data obtained from the first sample and second sample can be compared [0028]; [0029] discloses that at input function can be determined any number of times throughout a procedure and while determining the maximum blood concentrations; analyze changes in radiotracer uptake over time using two or more passes through a scanner [0019]; Patlak model to represent tracer dynamics [0040]); and
translating the scaled reference input function to generate the third candidate input function (the method may include the steps of identifying the maximum blood concentration, determining the input function after the maximum blood concentration has been reached, imaging a target organ or tissue, determining an input function, and reimaging the target organ or tissue. The steps of determining an input function and reimaging the target organ or tissue can be repeated any number of times [0029]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include the third candidate input function is determined by: generating a scaled reference input function by scaling the reference input function or a portion of the reference input function corresponding to a period after tb1 having the same duration as the period tb3 to tb5; and translating the scaled reference input function to generate the third candidate input function, as taught by Uber, in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 31, modified Kadrmas teaches the system of claim 26, as discussed above. Kadrmas further teaches wherein the relationship function between the compartment model, the input function, and the at least one PET image is represented using the following equation:
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where t denotes a time point, X(t) denotes a PET image corresponding to the time point t; Vb denotes a concentration of the plasma in the tissue; ; C, denotes a concentration of the tracer in a first compartment; C, denotes a concentration of the tracer in a second compartment; Cp denotes the input function; ki denotes a forward transport rate of the tracer from the plasma to the first compartment; k2 denotes a backward transport rate of the tracer from the first compartment to the plasma; k3 denotes a phosphorylation rate of the tracer; ⊗ denotes a convolution operation (Under these compartment models, the activity concentration A(t) of the extravascular tissue compartments for each tracer can be written:… where {ki} are the rate constants, λ is the radioactive decay constant, b(t) is the input function (concentration of freely exchangeable tracer in the blood), {circle around (×)} is the convolution operator, and * is used to denote either PTSM or ATSM since the same model was used for each….where fB is the vascular fraction in the ROI and B(t) is the total activity concentration in the whole blood (including both tracers when present) [0135]; [0060]-[0061] discloses compartment modeling).
Regarding claim 32, modified Kadrmas teaches the system of claim 12, as discussed above. Kadrmas, however, does not teach wherein the scan period of the dual injection scan is less than or equal to 10 minutes. Leahy, however, teaches wherein the scan period of the dual injection scan is less than or equal to 10 minutes (The patient may be moved through in discrete steps as illustrated in FIG. 4 with list-mode data acquired for a period of typically 1-5 minutes at each step [0045])
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include the scan period of the dual injection scan is less than or equal to 10 minutes, as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
Regarding claim 33, modified Kadrmas teaches method of claim 1, as discussed above. Kadrmas, however, does not teach wherein the determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period after the time point tb0 based on the first candidate input function, the first portion, and the second portion comprises: determining a ratio of the first portion to the second portion; and determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion.
Uber is considered analogous to the instant application as “System and method for rapid quantitative dynamic molecular imaging scans” is disclosed (title).
Uber, however, teaches:
wherein the determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period after the time point tb0 based on the first candidate input function and a ratio of the first portion to the second portion comprises (a radiopharmaceutical may be administered to a patient and a first sample may be obtained from the patient a first time period after administration. A second sample may be obtained after a second time period after administration, and the emission data obtained from the first sample and second sample can be compared [0028]; the input function may be determined two or more times throughout a procedure [0022]; The analyzer uses the data from the imaging system 110 to first determine the input function [0075]):
determining the ratio of the first portion to the second portion(For example, the system 10 may allow the user to program the injector 140 to inject a tracer 141 at a certain rate … The system 10 may also allow the user to program the injector 140 to inject several discrete doses of tracer over a period of time, for example, one 10 ml injection every 5 minutes or 10 minutes for 30 minutes or 40 minutes… a certain dose of tracer 141 may be administered when the input function reaches a particular lower threshold, [0048]; FIG. 4 a shows the general timeline of the procedure [0078]; FIG. 4 c illustrates in detail how the injector could be programmed to accomplish this protocol [0079] figs. 4A and 4C, reproduced below, show the time and amount of concentration delivered at each time point, these can be used to determine ratios, the maximum blood concentration, which is used for the input function calculation, is calculated after each administration of the tracer); and
determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion (functions (the input function may be determined two or more times throughout a procedure. In certain embodiments, the imaging data collected from the sample tissue can be normalized based on multiple input functions determined throughout the procedure [0022]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include the determining a second candidate input function that reflects a concentration change of the tracer in the subject during a period after the time point tb0 based on the first candidate input function, and a ratio of the first portion to the second portion comprises: determining the ratio of the first portion to the second portion; and determining the second candidate input function based on the first candidate input function and the ratio of the first portion to the second portion, as taught by Uber, in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 34, modified Kadrmas teaches the claimed invention as discussed above. Kadrmas, further teaches wherein a shape of the second candidate input function (fig. 11, snippet reproduced below, depicts a plot of tracer time activity curve of a staggered injection, both tracers injections have two shapes that are related and the shape of the function accounts for tracer decay from the two tracer injections; Fig. 11 [0023]) is determined based on the first candidate input function and the ratio of the first portion to the second portion ([0049] discloses that the a single tracer injected repeatedly, or a combination of tracers using multiple-timepoint or dynamic scanning, where the tracer administrations are simultaneous or staggered in time such that some or all of the PET timeframes, images, data, and/or datasets contain overlapping signals from more than one of the tracer administrations)
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Fig. 11 reproduced above
Regarding claim 35, modified Kadrmas teaches the method of claim 1, as discussed above. Kadrmas, however, does not teach wherein the reference input function starts from the time point tb4 and ends at the time point tb1, and the operations further include: determining a third candidate input function based on the first portion, the second portion, and the reference input function, the third candidate input function reflecting a concentration change of the tracer in the subject during a period after the scan period, the period starting from the time point tb3 and ending at a time point tb5.
Uber teaches wherein the reference input function starts from the time point tb4 and ending at the time point tb1, and the operations further include: determining a third candidate input function based on the first portion, the second portion, and the reference input function, the third candidate input function reflecting a concentration change of the tracer in the subject during a period after the scan period, the period starting from the time point tb3 and ends at a time point tb5 (([0029] discloses that at input function can be determined any number of times throughout a procedure and while determining the maximum blood concentrations; analyze changes in radiotracer uptake over time using two or more passes through a scanner [0019]; Patlak model to represent tracer dynamics [0040]; the reference input function is the initial input function after first measuring the maximum blood concentration, and the plurality of candidate input functions are the measurements that are taken afterwards).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include wherein the reference input function starts from the time point tb4 and ending at the time point tb1, and the operations further include: determining a third candidate input function based on the first portion, the second portion, and the reference input function, the third candidate input function reflecting a concentration change of the tracer in the subject during a period after the scan period, the period starting from the time point tb3 and ends at a time point tb5, as taught in Uber, in order to more accurately assess the uptake of the tracer and diffusion or circulation of the tracer through the target organ, as suggested by Uber ([0022]).
Regarding claim 36, modified Kadrmas teaches the system of claim 1, as discussed above. Kadrmas, however, does not teach wherein the dual injection scan during the scan period from tb1 to tb3 is less than or equal to 10 minutes.
Leahy, however, teaches wherein the dual injection scan during the scan period from tb1 to tb3 is less than or equal to 10 minutes (The patient may be moved through in discrete steps as illustrated in FIG. 4 with list-mode data acquired for a period of typically 1-5 minutes at each step [0045])
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas to include wherein the dual injection scan during the scan period from tb1 to tb3 is less than or equal to 10 minutes as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
Regarding claim 37, modified Kadrmas teaches method of claim 1, as discussed above. Kadrmas, however, not teach wherein the input function is presented according to the following Equation:
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where t denotes a time point in the examination period; C,(t) denotes a value of the input function at the time point t; Cimage(t) denotes a value of one of the candidate input functions at the time point t; Cp0(t) denotes the reference input function; and y and µ denote scaling constants to satisfy µ Cp0(tb4)=Cimage(tb3), and
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.
Leahy is considered analogous to the instant application as “Direct Patlak Estimation from List-Mode PET Data” is disclosed (title).
Leahy teaches:
wherein the input function is presented according to the following Equation:
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where t denotes a time point in the examination period; C,(t) denotes a value of the input function at the time point t; Cimage(t) denotes a value of one of the candidate input functions at the time point t; Cp0(t) denotes the reference input function; and y and µ denote scaling constants to satisfy µ Cp0(tb4)=Cimage(tb3), and
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, ([0060]-[0062] discloses obtaining the input function using multiple constants/samples).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kadrmas to include, wherein the input function is presented according to the following Equation:
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where t denotes a time point in the examination period; C,(t) denotes a value of the input function at the time point t; Cimage(t) denotes a value of one of the candidate input functions at the time point t; Cp0(t) denotes the reference input function; and y and µ denote scaling constants to satisfy µ Cp0(tb4)=Cimage(tb3), and
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as taught by Leahy. Doing so would may improve image resolution, noise properties and diagnostic power, as suggested by Leahy ([0019]).
Claims 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kadrmas et al (US 20080230703 A1) in view of Leahy (US 20150363948 A1), Uber (US 20140119621 A1). and (US 20180303438 A1, hereinafter “Hu”).
Regarding claim 11, modified Kadrmas teaches the method of claim 1, as discussed above. Kadrmas, however is silent regarding the parametric image includes a Ki image that reflects a rate of tracer transport from the plasma to the tissue of the subject.
Hu is considered analogous to the instant application as “System and method for whole body continuous bed motion pet scanning with bi-directional data acquisition modes” is disclosed.
Hu teaches, wherein the parametric image includes a Ki image (reconstructing respective parametric image [0007]; Some embodiments employ a linear Patlak model to generate two parametric images: one for metabolism rate (abbreviated as “Ki”) and one for distribution volume (abbreviated as “dv”) [0030]; The unknown parameters ki and dv in equation (7) can be solved by linear regression, and their respective values at each voxel provide the ki and dv images for each slice. [0063]), that reflects a rate of tracer transport from the plasma to the tissue of the subject (Parametric PET imaging aims to image tracer kinetics over time [0004]; where ki is the metabolism rate (i.e., the volume of plasma from which a substance is completely removed per unit time [0061]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kadrmas include, the parametric image includes a Ki image, in order to provide more information for tissue pathology than traditional standard uptake value (SUV) imaging, as suggested by Hu ([0004]).
Response to Arguments
Applicant's arguments have been fully considered but they are not persuasive.
Applicant arguments on pages 14-17 regarding the 35 USC 103 rejection of claim 1 are premised upon the assertion that that the prior art does not teach the newly added amendments to claim 1, regarding:- “tb1 being a time point when a concentration of the tracer in the subject is in a declining stage”, “and is a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject”, and “modifying the reference input function, wherein a value of the modified reference input function at the time point tb4 is equal to a value of the second candidate input function at the time point tb4, and a value of the modified reference input function at the time point tb1 is equal to a value of the first candidate input function at the time point tb1; and generating the input function by combining the modified reference input function and the first and second candidate input functions”. In response, the examiner respectfully disagrees. The examiner notes that claim 1 contains 112(b) rejections as noted above. Further time point is taught in Kadrmas, which teaches multiple injections ([0043], [0093]) and a “declining stage”, as shown in fig. 11 and in the cited portions above
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Snippet of fig. 11 reproduced above with annotations
Leahy is relied upon to teach the reference input function being a population-based input function that is determined based on a plurality of sample input functions corresponding to a plurality of sample subjects other than the subject ([0043] and [0060]-[0061] discloses use of a population-based input function from a group/plurality of subjects), and Uber is relied upon to teach modification of the input function limitation ([0022]; [0079]), as noted in the rejection above. Accordingly, this argument is not persuasive.
Applicant arguments on page 17 regarding the 35 USC 103 rejection of claim 12, are premised upon the assertion that the claim does is allowable due to same reasons as discussed in claim 1. The examiner respectfully disagrees for the reasons above. The applicant further argues that the prior art does not teach the newly added limitation to claim 12 regarding the input function equation. The examiner notes that the claim contains 112(b) issues as noted in the rejection above, elements of the claim are taught in the prior art as noted in the rejection above. Accordingly, this argument is not persuasive.
The applicant arguments on pages 18 are premised upon the assertion that the remaining dependent claims rejected under 35 USC 103 are allowable due to dependency on an allowable claim. These arguments are not persuasive due to the reasons discussed above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, PASCAL M. BUI-PHO can be reached on (571) 272-2714. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.B./Examiner, Art Unit 3798
/PASCAL M BUI PHO/Supervisory Patent Examiner, Art Unit 3798
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