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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 12, 2024 was filed after the mailing date of the application on April 12, 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: According to MPEP 608.01(m), the present Office practice is to insist that each claim must be the object of a sentence starting with “I (or we) claim,” “The invention claimed is” (or the equivalent). Thus, the heading simply stating “CLAIMS” is not sufficient.
Appropriate correction is required.
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 12-14 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.
Regarding claims 12 and 13, the phrase "optionally" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 14, the phrases “preferably” and “even more preferably” render the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim(s) 1, 2, 5, and 16-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1).
As per Claim 1, Flohr teaches a computer-implemented method comprising the steps of:
receiving and/or generating at least two representations (R1 R1F, R2, R2F) of an examination region of an examination object, where the at least two representations (R1, R1F, R2, R2F) represent the examination region after administration of a contrast agent, where the at least two representations (R1, R1F, R2, R2F) are the result of a computed tomography examination of the examination region at different X-ray energies (computed tomography system including an x-ray emitter 8, [0046]; x-ray source 8 are required in a sequential recording method with different energies, [0055]; first contrast agent-assisted image of an object area is recorded with a first energy, a second contrast agent-assisted image of an object area is recorded with a second energy, [0056]),
generating a representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) on the basis of the at least two received representations (R1, R1F, R2, R2F), where the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) represents a signal intensity distribution brought about by the contrast agent in the examination region (the temporal change in the contrast agent signal is taken into account between the first and the third recording in that a contrast agent signal is determined, which corresponds to a recording with the first energy at the point in time of the second recording, the determination of the contrast agent signal, which corresponds to a recording with the first energy at the point in time of the second recording, typically takes place in an image-based manner, in other words in HU values, the contrast agent signal is thus known for a specific point in time with two energies, [0057]).
Flohr teaches by taking the temporal change in the contrast agent signal into account between the first and the third image, a multi-energy image is determined by means of the three recordings. The multi-energy image is for instance a virtual native image. The temporal change in the contrast agent signal is taken into account between the first and the third recording in that a contrast agent signal is determined, which corresponds to a recording with the first energy at the point in time of the second recording. The determination of the contrast agent signal, which corresponds to a recording with the first energy at the point in time of the second recording, typically takes place in an image-based manner, in other words in HU values. The contrast agent signal is thus known for a specific point in time with two energies. Then current methods can be used to calculate a dual-energy image on the recorded images with the newly determined contrast agent signal [0057]. Since there is a temporal change in the contrast agent signal between the first and the third image, this means that the contrast agent signal either decreases or increases. Thus, there is an α-fold addition of the contrast agent signal, where α is a negative (contrast agent signal decreases) or positive (contrast agent signal increases) number. Thus, Flohr teaches
generating a synthetic representation (S, S2, S2F) of the examination region, where the generation of the synthetic representation (S, S2, S2F) comprises an α-fold addition of the representation of the contrast agent signal (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) to one of the at least two received representations (R1, R1F, R2, R2F) or to a virtual non-contrast agent representation of the examination region, where α is a negative or positive real number [0057].
Flohr teaches the inventive method includes the multi-energy image involving each instance three-dimensional spatial images reconstructed from individual x-ray projections. As a result, the cited advantages of the inventive method can be transferred to three-dimensional spatial images. This is particularly important to medical diagnostics [0041]. Thus, it would have been obvious to one of ordinary skill in the art that the multi-energy image (synthetic representation) is output and displayed in order for a doctor to look at the multi-energy image and perform medical diagnostics based on the multi-energy image. Thus, Flohr teaches
outputting and/or storing the synthetic representation (S, S2, S2F) and/or transmitting the synthetic representation (S, S2, S2F) to a separate computer system [0041].
As per Claim 2, Flohr teaches x-ray source 8 is required in a sequential recording method with different energies [0055]. A first contrast agent-assisted image of an object area is recorded with a first energy. A second contrast agent-assisted image of an object area is recorded with a second energy [0056]. Thus, the first energy is different from the second energy, and thus one of the energies is at a lower X-ray energy than the other energy. Thus, Flohr teaches wherein the at least two representations (R1, R1F, R2, R2F) comprise a first representation (R1, R1F) (first contrast agent-assisted image) and a second representation (R2, R2F) (second contrast agent-assisted image), where the first representation (R1, R1F) was acquired at a lower X-ray energy than the second representation (R2, R2F) [0055-0056].
As per Claim 5, Flohr teaches wherein the generation of the synthetic representation (S, S2, S2F) (multi-energy image) comprises the step of:
α-fold addition of the representation of the contrast agent signal (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) to the second representation (R2, R2F) or to the virtual non-contrast agent representation [0056, 0057].
As per Claim 16, Claim 16 is similar in scope to Claim 1, except that Claim 16 is directed to a computer system comprising: a processor; and a memory that stores an application program configured to perform an operation when executed by the processor, said operation comprising the method of Claim 1. Flohr teaches a computer system comprising: a processor; and a memory that stores an application program configured to perform an operation when executed by the processor, said operation comprising the method (a computer program product, having program code, in order to execute an embodiment of the inventive method, if the program product is executed on a computer, the computer program product is stored on a computer-readable medium 13, from where it can be loaded into the processor, [0051]). Thus, Claim 16 is rejected under the same rationale as Claim 1.
As per Claims 17-19, these claims are each similar in scope to Claim 1, and therefore are rejected under the same rationale.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Drummond (US 20040101090A1).
Flohr is relied upon for the teachings as discussed above relative to Claim 2.
However, Flohr does not teach wherein the generation of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) comprises the step of:
- subtracting the second representation (R2, R2F) from the first representation (R1, R1F). However, Drummond teaches wherein the generation of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) comprises the step of:
subtracting the second representation (R2, R2F) from the first representation (R1, R1F) (acquire a first image of a contrast agent at a first energy during a first scan of a multi energy computed tomography (MECT) system, acquire a second image at a second energy during the first scan of the MECT, and subtract the second image from the first image to generate an enhanced image, [0010]; the second image is then subtracted from the first image to generate a final image of the contrast agent at an increased signal level, [0038]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the generation of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) comprises the step of:
- subtracting the second representation (R2, R2F) from the first representation (R1, R1F) because Drummond suggests that this is an efficient way to discriminate different quantities of contrast agent [0001, 0006, 0038].
19. Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Zhao (US 20230011644A1).
Flohr is relied upon for the teachings as discussed above relative to Claim 2.
However, Flohr does not teach wherein the generation of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) comprises the step of:
- setting the grey values or tone values of those pixels/voxels of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) that represent bone tissue, adipose tissue and/or air to zero. However, Zhao teaches in display against the rest of imaged object or ROI, a material including a contrast agent is represented with a selected color tone differentiable from that of the bone in the ROI [0885]. Thus, the material including a contrast agent is represented with a selected color tone, and the bone is represented with a tone value of zero. Thus, Zhao teaches wherein the generation of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) comprises the step of:
setting the grey values or tone values of those pixels/voxels of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) that represent bone tissue, adipose tissue and/or air to zero [0885].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the generation of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) comprises the step of:
- setting the grey values or tone values of those pixels/voxels of the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w, KR1, KR2) that represent bone tissue, adipose tissue and/or air to zero because Zhao suggests that this way, the doctor can easily see the tissue that he/she is interested in, and easily ignore the bone tissue which he/she is not interested in [0885].
20. Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Gross (US 20130274589A1).
Flohr is relied upon for the teachings as discussed above relative to Claim 2. Flohr teaches wherein the first representation (R1) and the second representation (R2) are representations of the examination region [0056].
However, Flohr does not teach wherein the first representation (R1) and the second representation (R2) are representations of the examination region in real space. However, Gross teaches that the representations are representations of the examination region in real space (using Fourier transforms, the data may be transformed to real-space, the transform provides MR data representing the contrast agents, tissue, and fluid, the MR data represents an area or volume of the patient, [0074]; MR or CT scanner, [0108]). Thus, this teaching from Gross can be implemented into the device of Flohr so that the first representation (R1) and the second representation (R2) are representations of the examination region in real space.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the first representation (R1) and the second representation (R2) are representations of the examination region in real space because Gross suggests that real space is space in the real world, and thus a doctor viewing the representations sees them in a space in the real world, which makes it easier for the doctor to perform medical diagnostics based on the representations [0074].
21. Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Bruder (US 20100074503A1).
Flohr is relied upon for the teachings as discussed above relative to Claim 2. Flohr teaches wherein the first representation (R1F) and the second representation (R2F) are representations of the examination region [0056].
However, Flohr does not teach wherein the first representation (R1F) and the second representation (R2F) are representations of the examination region in frequency space. However, Bruder teaches that the representations are representations of the examination region in frequency space (apply contrast agent, transformation of the CT data records to a local frequency space is then carried out, [0042]). Thus, this teaching from Bruder can be implemented into the device of Flohr so that the first representation (R1F) and the second representation (R2F) are representations of the examination region in frequency space.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the first representation (R1F) and the second representation (R2F) are representations of the examination region in frequency space as suggested by Bruder. It is well-known in the art that analyzing CT projection data in the frequency space allows for optimized dual-energy imaging, highly targeted noise filtering, and drastically faster computational reconstruction.
22. Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Habermehl (see citation below).
Flohr is relied upon for the teachings as discussed above relative to Claim 1.
However, Flohr does not teach wherein the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w) is a representation of the examination region in frequency space, the method further comprising the step of:
- weighting the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w) in frequency space with a frequency-dependent weight function (WF). However, Habermehl teaches wherein the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w) is a representation of the examination region in frequency space, the method further comprising the step of:
weighting the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w) in frequency space with a frequency-dependent weight function (WF) (frequency-domain techniques, p. 2, last paragraph; contrast enhanced perfusion-weighted MRI, p. 18642, 1st sentence).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w) is a representation of the examination region in frequency space, the method further comprising the step of:
- weighting the representation of the contrast agent signals (KRF, KRF,w, KR1F, KR1F,w) in frequency space with a frequency-dependent weight function (WF) as suggested by Habermehl. It is well-known in the art that this has the advantage of visualizing tissue hemodynamics rather than just static anatomy.
23. Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Brekenfeld (see citation below).
24. As per Claim 9, Flohr is relied upon for the teachings as discussed above relative to Claim 1.
However, Flohr does not teach wherein α is greater than 1. However, Brekenfeld teaches wherein α is greater than 1 (the first single-dose, low-field sequence was started 30 minutes after initial contrast agent administration, after the standard-dose, low-field sequence had been obtained, an additional dose of 0.1 mmol/kg gadoteridol was administered, a third administration of 0.1 mmol/kg gadoteridol (triple dose) was then performed, image acquisition was again performed 5 minutes after contrast agent administration, p. 267, left column, last paragraph - right column, first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that α is greater than 1 because Brekenfeld suggests that this way, the doctor can compare the image with the single dose with the image with the triple dose to see if there are any differences, and thus more accurately perform medical diagnostics (p. 267).
25. As per Claim 10, Flohr does not teach wherein α is greater than zero and less than 1. However, Brekenfeld teaches performing imaging with a single dose, then a double dose, then a triple dose (p. 267, left column, last paragraph- right column, first paragraph). It would have been obvious to one of ordinary skill in the art for a doctor to modify the doses as desired, and thus, α is greater than zero and less than 1. This would be obvious for the reasons given in the rejection for Claim 9.
26. Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Petersen (see citation below).
Flohr is relied upon for the teachings as discussed above relative to Claim 1.
However, Flohr does not teach wherein α is less than zero. However, Petersen teaches using two contrast agent (CA) doses. Contrast-enhanced MRI data were acquired after CA injection [0.1 mmol/kg body weight = single dose]. The measurement was repeated with double dose CA (0.2 mmol/kg body weight) (p. 2). It would have been obvious to one of ordinary skill in the art that this could be performed the other way around, with the double dose CA performed first, then the single dose CA, and thus, α is less than zero.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that α is less than zero because Petersen suggests that this way, the doctor can compare the image with the double dose CA with the image with the single dose CA to see if there are any differences, and thus more accurately perform medical diagnostics (p. 2).
27. Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1), Drummond (US 20040101090A1), Zhao (US 20230011644A1), Gross (US 20130274589A1), Bruder (US 20100074503A1), and Habermehl (see citation below).
Claim 12 is similar in scope to Claims 1-4 and 6-8, and therefore is rejected under the same rationale.
28. Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1), Drummond (US 20040101090A1), Zhao (US 20230011644A1), Gross (US 20130274589A1), and Habermehl (see citation below).
Claim 13 is similar in scope to Claims 1-4, 6, and 8, and therefore is rejected under the same rationale.
29. Claim(s) 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Karam (US 20170095578A1).
30. As per Claim 14, Flohr is relied upon for the teachings as discussed above relative to Claim 1.
However, Flohr does not teach wherein the contrast agent is an MRI contrast agent, preferably an intracellular MRI contrast agent, even more preferably a hepatobiliary MRI contrast agent. However, Karam teaches wherein the contrast agent is an MRI contrast agent, preferably an intracellular MRI contrast agent, even more preferably a hepatobiliary MRI contrast agent [0017].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the contrast agent is an MRI contrast agent, preferably an intracellular MRI contrast agent, even more preferably a hepatobiliary MRI contrast agent as suggested by Karam. It is well-known in the art that it makes it easier to detect liver metastases, characterize focal lesions, and evaluate biliary leaks.
31. As per Claim 15, Flohr does not teach wherein the contrast agent comprises gadoxetate disodium. However, Karam teaches wherein the contrast agent comprises gadoxetate disodium (method using gadoxetate disodium as a CT contrast agent, the technique with CT will generate images, [0047]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr so that the contrast agent comprises gadoxetate disodium as suggested by Karam. It is well-known in the art that it has a dual-contrast mechanism, which allows for both blood-vessel imaging and a hepatobiliary phase, and this dual action vastly improves the detection and characterization of small liver lesions like tumors and metastases.
32. Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Flohr (US 20140161227A1) in view of Rolfe (US 20210085886A1).
Claim 20 is similar in scope to Claim 1, except that Claim 20 is directed to a kit comprising the contrast agent and a non-volatile storage medium comprising a computer program that can be loaded into a working memory of a computer system, where it causes the computer system to execute the method of Claim 1. However, Flohr does not teach a kit comprising the contrast agent and a non-volatile storage medium comprising a computer program that can be loaded into a working memory of a computer system, where it causes the computer system to execute the method. However, Rolfe teaches a kit comprising the contrast agent [0005] and a non-volatile storage medium comprising a computer program that can be loaded into a working memory of a computer system, where it causes the computer system to execute the method (non-volatile memory 320 stores a control program of the microprocessor 315 and a volatile memory 325 is used as a working memory by the microprocessor 315, [0036]). Thus, Claim 20 is rejected under the same rationale as Claim 1 along with this additional teaching from Rolfe.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Flohr to include a kit comprising the contrast agent and a non-volatile storage medium comprising a computer program that can be loaded into a working memory of a computer system, where it causes the computer system to execute the method as suggested by Rolfe. It is well-known in the art that this way, the computer program can be loaded into the working memory when it is needed by the computer system, and the working memory can be used to store other data when that computer program is not needed by the computer system.
Prior Art of Record
1. Habermehl, Christina; Contrast enhanced high-resolution diffuse optical tomography of the human brain using ICG”; September 2011; Optics Express; Vol. 19; p. 18636-18644; https://opg.optica.org/oe/fulltext.cfm?uri=oe-19-19-18636
2. Brekenfeld, Caspar; Enhancement of Cerebral Diseases: How Much Contrast Agent Is Enough? Comparison of 0.1, 0.2, and 0.3 mmol/kg Gadoteridol at 0.2 T with 0.1 mmol/kg Gadoteridol at 1.5 T; January 2001; Investigative Radiology; Volume 36; p. 266-275; https://journals.lww.com/investigativeradiology/fulltext/2001/05000/Enhancement_of_Cerebral_Diseases__How_Much.4.aspx
3. Petersen, Steffen; Influence of Contrast Agent Dose and Image Acquisition Timing on the Quantitative Determination of Nonviable Myocardial Tissue Using Delayed Contrast-Enhanced Magnetic Resonance Imaging; July 2009; Journal of Cardiovascular Magnetic Resonance; Volume 6; p. 1-2; https://www.tandfonline.com/doi/abs/10.1081/JCMR-120030581
Conclusion
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JH
/JONI HSU/Primary Examiner, Art Unit 2611
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