Ex Parte Florent et alDownload PDFPatent Trial and Appeal BoardAug 21, 201814004195 (P.T.A.B. Aug. 21, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 14/004,195 09/10/2013 Raoul Florent 24737 7590 08/23/2018 PHILIPS INTELLECTUAL PROPERTY & STANDARDS 465 Columbus A venue Suite 340 Valhalla, NY 10595 UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www .uspto.gov ATTORNEY DOCKET NO. CONFIRMATION NO. 2011P00321WOUS 8999 EXAMINER MEHL, PATRICK M ART UNIT PAPER NUMBER 3737 NOTIFICATION DATE DELIVERY MODE 08/23/2018 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): patti. demichele@Philips.com marianne.fox@philips.com katelyn.mulroy@philips.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RAOUL FLORENT, CECILE DUFOUR, VINCENT AUVRA Y, and OD ILE BONNEFOUS 1 Appeal2017-002926 Application 14/004, 195 Technology Center 3700 Before JEFFREY N. FREDMAN, JOHN G. NEW, and RICHARD J. SMITH, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 Appellants state that the real party-in-interest is Koninklijke Philips Electronics N.V. App. Br. 3. Appeal2017-002926 Application 14/004, 195 SUMMARY Appellants file this appeal under 35 U.S.C. § I34(a) from the Examiner's Final Rejection of claims 1-12 and 16-24. Specifically, claims 1-5, 7, 9, 10, 12, 16, and 17 stand rejected as unpatentable under 35 U.S.C. § 101 as being directed to nonstatutory subject matter. Claims 1-5, 7, 9, 10-12, 16, and 17 also stand rejected as unpatentable under 35 U.S.C. § I03(a) as being obvious over the combination ofBredno et al. (US 2009/0116715 Al, May 7, 2009) ("Bredno"), I. Waechter et al., Model-based blood flow quantification from rotational angiography, 12 MED. IMAGE ANAL. 586-602 (2008) ("Waechter"), A.P. Yoganathan et al., Review of Hydrodynamic Principles for the Cardiologist: Applications to the Study of Blood Flow and Jets by Imaging Techniques, 12 J. AM. COLL. CARDIO. 1344--53 (1988) ("Yoganathan"), D.J. Hawkes et al., Development of a Model to Predict the Potential Accuracy of Vessel Blood Flow Measurements from Dynamic Angiographic Recordings, in MATHEMATICS AND COMPUTER SCIENCE IN MEDICAL IMAGING, F39 NATO ASI Series 469-78 (2008) ("Hawkes"), and Flohr et al. (US 2009/0274358 Al, November 5, 2009) ("Flohr"). Claim 8 stands rejected as unpatentable under 35 U.S.C. § I03(a) as being obvious over the combination of Bredno, Waechter, Yoganathan, Hawkes, Flohr, and S. Hayashi et al., New Measurement of Hepatic Blood Flow by Xenon CT System: An Animal Study with PGEJ, 129 J. SURG. REs. 24--30 (2005) ("Hayashi"). Claims 18 and 23 stand rejected as unpatentable under 35 U.S.C. § I03(a) as being obvious over the combination of Bredno, Waechter, Yoganathan, Hawkes, Flohr, and A.S. Kapoor, Techniques of Cardiac 2 Appeal2017-002926 Application 14/004, 195 Catheterization and Coronary Angiography, in INTERVENTIONAL CARDIOLOGY 10-21 (A. S. Kapoor, ed.) (1989) ("Kapoor"). Claims 19, 22, and 24 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Bredno, Waechter, Yoganathan, Hawkes, Flohr, Kapoor, and Amoud W.J. van 't Hof et al., Angiographic Assessment of Myocardial Reperfusion in Patients Treated With Primary Angioplasty for Acute Myocardial Infarction, Myocardial Blush Grade, 97 CIRCULATION 2302---06 (1998) ("van 't Hof'). Claim 6 stands rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Bredno, Flohr, Waechter, and Y oganathan. Claim 20 stands rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Bredno, Flohr, Waechter, Y oganathan, and Kapoor. Claim 21 stands rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Bredno, Flohr, Waechter, Y oganathan, Kapoor, and van 't Hof. We have jurisdiction under 35 U.S.C. § 6(b ). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellants' invention is directed to x-ray imaging technology as well as image post-processing and particularly to post-processing of perfusion image data acquired by an x-ray imaging apparatus by absolutely or relatively normalizing perfusion image data to allow a preferred comparison of the image data. Abstract. 3 Appeal2017-002926 Application 14/004, 195 REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. An apparatus configured for perfusion assessment, compnsmg: a contrast agent injection device for injecting contrast agent in a blood vessel; App. Br. 52. a medical imaging device; and circuitry configured to: a) derive a total volume flow in said blood vessel; b) using imaging output of said medical imaging device, determine an amount of a contrast agent in a blood vessel; and c) based on the derived flow and the determined amount, normalize perfusion data. ISSUES AND ANALYSES We reject the Examiner's conclusion that the claims are directed to nonstatutory subject matter. We are persuaded by, and expressly adopt, the Examiner's findings, reasoning, and conclusions establishing that Appellants' claims are prima facie obvious over the combined cited prior art. We address the arguments raised by Appellants below. 4 Appeal2017-002926 Application 14/004, 195 A. Rejection of claims 1-12 and 16-24 under 35 U.S.C. § 101 Issue Appellants argue that the Examiner erred in finding that the claims are unpatentable as being directed to an abstract idea. App. Br. 7. Analysis The Examiner finds that the claims are directed to the abstract idea of calculating perfusion volume and normalizing perfusion images for dynamically calculating the contrast agent perfusion. Final Act. 5. Specifically, the Examiner finds that the claims are directed to the abstract idea of normalizing a time sequence of images with a calculated value determined from image analysis normalizing. Id. The Examiner finds that the claims are therefore directed to a mathematical procedure for converting one form of numerical representation to another. Id. The Examiner finds that the additional steps recited in the claims, including measuring, estimating, calculating concentrations and flow values for generating volume flow, blood flow and contrast agent flow rates, as well as contrast imaging and the associated image analysis for the concerning subject, are well-understood, routine, and conventional activities well known to those of ordinary skill in the art (i.e., routine data collection). Final Act. 6. The Examiner therefore concludes that these steps do not amount to "significantly more" than the abstract idea of normalization itself. Id. The Examiner additionally finds that the claims do not require using any specific device for performing the claimed calculation, i.e., using ratios 5 Appeal2017-002926 Application 14/004, 195 and simple mathematical or statistical functions that can be done with any generic calculator or processor. Final Act. 6. We do not agree. Appellants' claims are directed to the use of a contrast agent injection device for injecting contrast agent in a blood vessel, a medical imaging device, and circuitry configured to perform the claimed functions, i.e., derive a total volume flow in said blood vessel and, using the imaging output of the imaging device, determining an amount of a contrast agent in a blood vessel and normalizing the perfusion data. In performing a patentability analysis under 35 U.S.C. § 101, we follow the framework set forth by the Supreme Court in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012). As a first step, we determine whether the claims at issue are directed to a patent-ineligible concept, i.e., a law of nature, a phenomenon of nature, or an abstract idea. Mayo, 566 U.S. at 70-71. If the claims are so directed, we next consider the elements of each claim both individually and "as an ordered combination" to determine whether additional elements "transform the nature of the claim" into a patent-eligible application. Id. at 78-79; see also Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1375 (Fed. Cir. 2015). Specifically, the Supreme Court considered this second step as determining whether the claims recite an element or combination of elements that is "sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the [ineligible concept] itself." Id. at 72-73. The Examiner finds that the claims are directed to an abstract idea, i.e., an algorithm for transforming one set of numbers into another set. We do not disagree with the Examiner that at the heart of the claims on appeal is the use of machine-computed algorithms to derive a set of values, i.e., the 6 Appeal2017-002926 Application 14/004, 195 total volume flow through the imaged vessel, the amount of contrast agent in the vessel, and normalizing the perfusion data. But the fact that the method employs a mathematical algorithm (an abstract idea) does not put an end to our analysis. The recitation of an algorithm, without additional limitations, is generally not patent-eligible. See Digitech Image Techs., LLC v. Elecs. for Imaging, Inc., 758 F.3d 1344, 1351 (Fed. Cir. 2014) ("Without additional limitations, a process that employs mathematical algorithms to manipulate existing information to generate additional information is not patent eligible"). However, "a process is not unpatentable simply because it contains a law of nature or a mathematical algorithm." Diamond v. Diehr, 450 U.S. 175, 187 (1981). If the process recited in the claims is new and useful itself, beyond the mathematical algorithm, the claimed method may be patent eligible. See Parker v. Flook, 437 U.S. 584, 591 (1978). Indeed, we find that Diehr is instructive in this analysis. In Diehr, the Appellants' claims recited use of an algorithm, the Arrhenius equation, in the process of curing synthetic rubber. Diehr, 450 U.S. at 187. The Supreme Court found that the claims: do not seek to patent a mathematical formula. Instead, they seek patent protection for a process of curing synthetic rubber. Their process admittedly employs a well-known mathematical equation, but they do not seek to pre-empt the use of that equation. Rather, they seek only to foreclose from others the use of that equation in conjunction with all of the other steps in their claimed process. These include installing rubber in a press, closing the mold, constantly determining the temperature of the mold, constantly recalculating the appropriate cure time through the use of the formula and a digital computer, and automatically opening the press at the proper time. Obviously, one does not need a "computer" to cure natural or synthetic rubber, but if the 7 Appeal2017-002926 Application 14/004, 195 Id. computer use incorporated in the process patent significantly lessens the possibility of "overcuring" or "undercuring," the process as a whole does not thereby become unpatentable subject matter. In the appeal before us, Appellants' claims use data derived from imaging of contrast agent-perfused blood vessels to determine total volume flow rate in the vessel, the amount of the contrast agent in the vessel; and further using this data, normalizing the perfusion data. We find that, as in Diehr, Appellants are not attempting to claim the algorithm itself, but rather the use of the algorithm in determining flow rate, contrast agent amount, and normalizing the data. We contrast this with the Supreme Court's holding in Parker, in which the Court found unpatentable claims that the application sought to protect a formula for computing an "alarm limit," or in Gottschalk v. Benson, in which the Court held unpatentable claims for an algorithm used to convert binary code decimal numbers to equivalent pure binary numbers. 409 U.S. 63, 71-72 (1972). In summary, we find that, although the limitations of the claims on appeal incorporate an abstract idea, the claims recite substantially more than an attempt to claim only the algorithm itself, such that the claims exceed the impermissible stating of an algorithm and adding the words "apply it." Mayo, 566 U.S. at 72. We consequently reverse the Examiner's rejection of the claims on this ground. 8 Appeal2017-002926 Application 14/004, 195 B. Rejections of claims 1-12 and 16-24 under 35 U.S.C. § 103(a) 1. Claim 6 Issue Appellants argue that the Examiner erred in failing to demonstrate a rational underpinning to combine the references, or the manner in which the cited combined prior art teaches or suggests all of the limitations of claim 6. App. Br. 26. Analysis Claim 6 recites: A method for dynamic normalization of data for perfusion comparison and quantification, comprising the steps of determining an amount of a contrast agent in a blood vessel; and normalizing perfusion data based on the determined amount of contrast agent in the blood vessel, wherein the amount of contrast agent is determined by determining an integrated volume of contrast agent flowing through a defined section of the blood vessel. App. Br. 53. The Examiner finds Bredno teaches a C-arm X-ray angiography device for the detection of motion and corrections involved in the determination of flow dynamics, especially blood flow within a patient. Final Act. 20 ( citing Bredno ,r,r 1-2, Fig. 1 ). The Examiner also finds Bredno teaches a CPU for controlling, storing and performing any necessary functions. Id. ( citing Bredno Fig. 3). The Examiner also finds that Bredno 9 Appeal2017-002926 Application 14/004, 195 teaches that the processing element is adapted to determine a total volume flow, or an amount of a contrast agent in a blood vessel, with local determination of the contrast agent concentration (Bredno ,r,r 7 0-71) utilizing a calibration and mask determination with preliminary image sequences with no contrast agent imaging followed by high dilution of contrast agent imaging. Final Act. 20 (citing Bredno ,r,r 18-19, 70-71, 66). The Examiner therefore finds that Bredno teaches determining the time intensity curves of contrast agent concentration on the basis of two different points, providing a direct relation, after calibration of the intensity curves, between the contrast agent concentration and the image contrast or pixel opacity. Id. ( citing Bredno ,r 18). The Examiner also points out that it was well known in the art of fluid dynamics at the time of invention that the total amount of a liquid or element passing through a section corresponding to one position/section on the blood vessel, during an interval is equal to the integrated volume of the liquid or element flowing though that section during that period of time. Final Act. 26. The Examiner acknowledges that Bredno does not expressly teach that the processing element provides dynamic normalization based on the determined total volume flow or amount of contrast agent in the blood vessel and does not teach the integral of the volume of contrast agent flowing through the blood vessel. Final Act. 21. The Examiner cites Flohr and Waechter as teaching that the processing element provides the dynamic normalization based on the determined total volume flow or amount of contrast agent in the blood vessel. Id. 10 Appeal2017-002926 Application 14/004, 195 The Examiner finds Flohr discloses a method of tomography employing normalizing image analysis with respect to the contrast in the image data produced by the amount of contrast agent. Final Act. 21 ( citing Flohr ,r 2). The Examiner finds Flohr teaches that the dynamic aspect of the contrast imaging process and the process of normalization minimize the effects of examination-specific and patient-specific parameters during the examination. Id. ( citing Flohr ,r 42). The Examiner finds that Flohr teaches normalization via the calculation of a reference value representative of the amount of contrast agent within the reference blood vessel and through which the image data will be divided. Id. ( citing Flohr ,r 51 ). The Examiner also finds that Flohr therefore teaches that normalization is determined with a characteristic parameter representative of the amount of the contrast agent within the blood vessel, or downstream of the defined section. Id. With respect to Waechter, the Examiner finds the reference teaches a method for blood quantification from rotational angiography, by which flow maps are calculated from images of blood vessel images, and in which the intensity or contrast depends directly on the concentration of an injected contrast agent over time. Final Act. 22 (citing Waechter 587). The Examine further finds that Waechter teaches that the relation between the amount of the contrast agent injected at the site of injection, the total flow rate, and the contrast injection rate can be modeled. Id. (citing Waechter 590, Figs. 4a- b ). The Examiner finds that Waechter also teaches calibration of the opacity or attenuation caused by the concentration of the contrast agent within the considered fluid to directly calibrate the concentration of the 11 Appeal2017-002926 Application 14/004, 195 contrast agent with the measured image intensity. Final Act. 22 ( citing Waechter 594). The Examiner concludes that it would have been obvious for a person of ordinary skills in the art to have combined the apparatus and method of Bredno with a normalization method using a ratio with the amount of contrast agent within the blood vessel and using the reference value representative of the amount of the contrast agent within the blood vessel as normalization factor for the image data, as taught by Flohr. The Examiner concludes that a person of ordinary skill would be motivated to combine the teachings of the references so as to dynamically minimize the motions and deformations that occur during image acquisition, and to minimize the fluctuations caused during the injection procedure. Final Act. 22-23. The Examiner further finds that it would have been obvious to combine the teachings of Bredno and Flohr with the teachings of Waechter to account for the direct relationship between the total amount of contrast agent being injected and the total volume flow as taught by the latter. Final Act. 23. By this means, the Examiner concludes, the total volume flow as a characteristic relative value of the total contrast agent total amount in the blood vessel can be determined and a dynamic normalization, as taught by Flohr, can be performed to assess the integrity of the cardio or cerebrovascular system. Id. The Examiner acknowledges that the combined teachings of Bredno, Flohr, and Waechter do not teach or suggest calculation of integrated volume of contrast agent flowing through a defined section of the blood vessel. Final Act. 23. The Examiner therefore points to Y oganathan as teaching that the total flow volume which can related to the total volume of 12 Appeal2017-002926 Application 14/004, 195 contrast agent passing through the defined section by relating the volume flow rate to the volume of the contrast agent flowing through the section. Id. The Examiner finds that Y oganathan teaches that the total volume of contrast agent present downstream to the section is therefore the integrated volume of contrast agent flowing through the upstream section. Id. at 23- 24. The Examiner concludes that it would have been obvious for a person of ordinary skills in the art to have combined the apparatus and method of Bredno, Flohr, and Waechter, as explained supra, with the determination of amount of contrast agent downstream to a defined section of the vessel as the integral of the volume amount of the contrast agent flowing through that section as taught by Y oganathan. Final Act. 24. Appellants first argue that Bredno provides no teaching or suggestion relating to perfusion as that term is used in the instant claims. App. Br. 16. Appellants point to their Specification, which defines perfusion as: "the passage of fluid through a lymphatic system or blood vessels up to and into an organ or tissue." Id. (quoting Spec. 1). Appellants next argue that the Examiner provides no explanation how the teachings of Bredno would have been modified by Flohr. App. Br. 16. Appellants speculate that Bredno' s teaching of monitoring perfusion "around the 'suspicious vessel segment"' could be implemented in view of Flohr's perfusion normalization. Id. Therefore, Appellants imagine, a reference vessel, or segment thereof, upstream of and feeding the suspicious vessel segment would be selected. Id. According to Appellants, Flohr teaches using a reference vessel, or vessel segment, upstream of the region subject to perfusion analysis. App. 13 Appeal2017-002926 Application 14/004, 195 Br. 17. Specifically, Appellants assert, the perfusion analysis region is the region that is being compared over separate times for the same individual, or instead for different individuals. Id. Therefore, Appellants contend, Flohr, by teaching the selection of a reference vessel or segment sufficiently upstream of the perfusion region to be examined, teaches using an area sufficiently pure in its reflection of "changes in patient-specific and/or examination-specific parameters." Id. (citing Flohr ,r,r 13, 11). Appellants argue that Flohr teaches that the reference measurement thereby tends to be independent of observation related to the underlying anatomical or functional aspects of the perfusion region. Id. ( citing Flohr ,r,r 14, 12 ). Appellants argue further that the reference vessel segment of Flohr would accordingly be located sufficiently upstream of the Bredno "suspicious vessel segment," e.g., a stenosis site, because the stenosis related to the perfusion region being analyzed in Bredno, and because the contrast agent concentration is disturbed in a stenosis region. App. Br. 18 ( citing M. Xu et al., Simulation of Contrast Agent Transport in Arteries with Multilayer Arterial Wall: Impact of Arterial Transmural Transport on the Bolus Delay and Dispersion, 2014 THE SCIENTIFIC WORLD JOURNAL 5 (2014) ("Xu"); see also Spec. 3). Therefore, Appellants argue, the Bredno/Flohr reference vessel segment, would be upstream of, and would feed, the stenosis site, and would, for purposes of perfusion normalization, measure a pixel-value average at that upstream location. App. Br. 18. Furthermore, Appellants assert, there would be no such measurement downstream of the stenosis site and the contrast agent injection site would be similarly upstream. Id. 14 Appeal2017-002926 Application 14/004, 195 Appellants contrast the means by which normalization measurement is taught by Flohr ( average pixel values along the reference segment) with Bredno' s teaching of a time-intensity curve at fixed locations as determining an average for that location. App. Br. 19. Appellants argue that Bredno teaches that determination of "the total volume flow" in the vessel is the desired end goal and used to assess the state of the steno sis. Id. ( citing Bredno ,r,r 18, 37). Appellants argue that therefore there is no disclosure or suggestion of using this end goal parameter to "normalize perfusion data" as recited in the claims, because neither Bredno nor Flohr expressly teach this as a desired goal. Id. Appellants next argue that Waechter neither teaches nor suggests normalizing perfusion data. App. Br. 20. Rather, Appellants argue, Waechter teaches that, given some simplifying assumptions, the instantaneous contrast agent concentration at the site of injection is equal to the ratio of the instantaneous injection flow rate to the instantaneous total flow rate. Id. at 21 (citing Waechter Eq. 11). Appellants assert, however, that Waechter offers no teaching or suggestion that its ratio can serve as a factor in a mathematical expression that is integrated over time. Id. Nor, Appellants argue, do any of the references cited by the Examiner teach or suggest any such instantaneous contrast agent concentration factor for determining "an amount of a contrast agent in a blood vessel ... by determining an integrated volume of contrast agent flowing through a defined section of the blood vessel." Id. With respect to Y oganathan, Appellants argue that the reference teaches that fluid flow through a vessel is not uniform, but varies radially, and that flow velocity can also vary over time. App. Br. 22. Appellants 15 Appeal2017-002926 Application 14/004, 195 acknowledge that Y oganathan also teaches that an instantaneous volume flow rate can be integrated over time. Id. ( citing Y oganathan Eq. 8). Appellants state that it is unclear to them what this reference to integrating an instantaneous volume flow rate over time has to do with the Examiner's rejection of claim 6. Appellants' remaining arguments are diffuse and largely repetitive of the arguments presented above. See App. Br. 25-32. We do not find Appellants' arguments persuasive. As an initial matter, we agree with Appellants' contention that their Specification defines the claim term "perfusion" as meaning: "the passage of fluid through a lymphatic system or blood vessels up to and into an organ or tissue. Perfusion scanning is thus the process by which the perfusion can be observed, recorded and quantified." Spec. 1. However, we do not see the relevance of their argument. Flohr explicitly teaches that: In the method according to at least one embodiment of the invention, image data to be normalized with respect to a contrast of an examination region in the image data produced by a contrast agent is provided with the aid of imaging diagnostic medical equipment. The image data of the examination region illustrates a tissue structure to be examined and at least part of a blood vessel system connected to the tissue structure, which are at least in part permeated by contrast agent. Flohr ,r 9 ( emphasis added). Flohr thus expressly teaches normalizing imaging of passage of fluid through blood vessels up to and into an organ or tissue, as defined by Appellants' Specification. And whereas it is true that, as in the case of Bredno, the other references refer to measurement of the flow of contrast agent in other vascular locations, e.g., upstream or downstream of a stenosis: 16 Appeal2017-002926 Application 14/004, 195 [t]he test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413,425 (C.C.P.A. 1981). Appellants do not dispute that all of the references are analogous art, both to each other and to the claims on appeal. Bredno, Flohr, and Waechter, as well as the claims, are all directed to methods of imaging, with the use of a contrast, vascular flow by one method or another. Y oganathan is cited as evidence that it was well known in the art that total flow ("Q(T)") can be determined by integrating the volume flow rate over position and time. See Yoganathan 1349. The Examiner cites Bredno as teaching a method of measuring total volume flow through a vessel, be measuring flow at two different points: According to another exemplary embodiment of the present invention, the analysis unit is further adapted for determining a time intensity curve of contrast agent concentration on the basis of at least the first position of the first marker and a second position of a second marker, and performing a model-based flow analysis adapted to determine at least one of a total volume flow and a pressure decline, even in the presence of strong pulsation effects. Therefore, by collecting time intensity curves of contrast agent concentration from at least two well-defined points in a moving coronary, a model-based flow analysis adapted for total volume flow determination ... in a vessel may be possible, even in the presence of strong pulsation effects. 17 Appeal2017-002926 Application 14/004, 195 Bredno ,r,r 18-19. In other words, Bredno teaches that it is possible, by constructing time intensity functions from imaging of the contrast agent concentration at upstream and downstream positions to perform a model- based analysis of flow to determine total volume flow. Flohr teaches normalizing data from images obtained by injection of a contrast agent. Specifically, Flohr is directed to, inter alia: [A] method [by which] image data of the examination region is provided with the aid of the tomography scanner. At least one section of a reference vessel permeated by contrast agent is selected in the image data. The image data is normalized on the basis of image data from the section of the reference vessel such that the contrast in the image data as a result of the contrast agent is almost independent of patient-specific and examination- specific parameters in order to ensure that image data from different times can be compared. Flohr Abstr. We agree with the Examiner that, by combining the teachings of Bredno and Flohr, it would have been obvious to dynamically normalize, from repeated trials, the data of Bredno relating to the contrast agent concentration obtained by constructing time intensity functions at given points on the vessel segment in question. The Examiner further relies on Waechter as teaching a direct relationship between the total amount of contrast agent injected and the total volume flow. See Final Act. 23. Waechter is directed to: "us[ing] a model of contrast agent dispersion to determine the flow parameters from the spatial and temporal progression of the contrast agent concentration, represented by a flow map." Waechter Abstr. Specifically, Waechter teaches that: [W]e describe our flow quantification method and our flow model. During the flow quantification the model can be 18 Appeal2017-002926 Application 14/004, 195 constrained using different information, for example about the injection or from an attenuation calibration .... Our method first determines a so-called flow map and reliability map from the rotational sequence. A flow map is represented as an image, in which the intensity depends on the concentration of contrast agent, and where the horizontal dimension is time t and the vertical dimension is length 1 along the vessel. It represents the contrast agent propagation through the vessel. The characteristic pattern of the flow map provides information about the mean volumetric mean flow rate and the flow waveform .... Waechter 587 (emphasis added). We thus agree with the Examiner that Waechter teaches that the intensity of the flow map is directly dependent upon the concentration of the contrast agent as it moves along the length of the studied vessel. Finally, as we have explained supra, we agree with the Examiner that Y oganathan teaches that it was well known in the art that total flow ("Q(T)") can be determined by integrating the volume flow rate over position and time. Yoganathan 1349. Claim 6 requires: (1) determining an amount of a contrast agent in a blood vessel by determining an integrated volume of contrast agent flowing through a defined section of the blood vessel; and (2) normalizing perfusion data based on the determined amount of contrast agent in the blood vessel. The combination of Bredno, Waechter, and Yoganathan teach that the intensity of the contrast agent is a direct measure of the concentration of the concentration present and can be measured as a function of flow (Waechter), that the velocity of the flow through the vessel can be measured by constructing time intensity functions in the vessel (Bredno ), and that it was 19 Appeal2017-002926 Application 14/004, 195 well known that the total volume flow of contrast agent through the segment is the integral of volume flow rate over position and time (Yoganathan). Furthermore, Flohr teaches normalizing concentration (i.e., intensity of contrast agent as a function of contrast agent concentration) over multiple trials. We agree with the Examiner's findings and conclusion that claim 6 is obvious over the cited prior art. We consequently affirm the Examiner's rejection of claim 6. Furthermore, Appellants rely upon the same arguments with respect to claim 20 and, for the reasons explained, we similarly affirm the Examiner's rejection. See App. Br. 33. 2. Claim 21 Issue Appellants argue that the Examiner erred because van 't Hof fails to teach or suggest the limitation of claim 21 reciting: "said placing being such that backflow of the injected contrast agent occurs in said blood vessel, the integrating being based on flow through a cross-section of said blood vessel disposed beyond said backflow." App. Br. 33. Analysis Appellants repeat their arguments presented supra, adding that van 't Hof fails to cure the alleged deficiencies of the cited prior art. Id. at 32. Appellants note that that claim 21 depends from claim 20, which recites, in relevant part: "Parent claim 20 recites, "placing a catheter tip at said ostium, thereby entering said blood vessel; and injecting said contrast agent through the placed catheter tip." App. Br. 33. Appellants argue 20 Appeal2017-002926 Application 14/004, 195 further that van 't Hof teaches merely that it was known that backflow exists. Id. Appellants acknowledge that they are not claiming to have discovered backflow. Id. Appellants contend that there is no teaching or suggestion in van 't Hof of the sufficiently upstream cross-section being sufficiently beyond an ostium so as to be beyond the backflow. Id. The Examiner responds that van 't Hof teaches that the backflow is used as a method to make sure that the contrast agent is filling the artery in a continuous manner. Ans. 23. The Examiner finds that this teaching therefore suggests that the integrating step is performed through a cross- section in a region where the contrast agent is filling the artery without disturbance such as beyond the backflow region, as would have been recognized by a person of ordinary skill in the art. Id. The Examiner further finds that such a person of ordinary skill would have recognized that the placement of the cross-section would have been a matter of choice of engineering design to achieve a proper analysis of the contrast uniform propagation along the artery. Id. We are not persuaded by Appellants' arguments. van 't Hof teaches: In each patient, the best projection was chosen to assess the myocardial region of the infarct-related coronary artery, preferably without superpositioning of noninfarcted myocardium .... Angiographic runs had to be long enough to allow some filling of the venous coronary system, and backflow of the contrast agent into the aorta (Hexabrix, 5 to 15 mL) had to be present to be certain of adequate contrast filling of the epicardial coronary artery. van 't Hof 2303. We agree with the Examiner that, based upon the teachings of van 't Hof, it would have been obvious to a person of ordinary skill in the art to place the cannula for injecting the contrast agent in a location such that 21 Appeal2017-002926 Application 14/004, 195 observed backflow would ensure that there would be sufficient filling of the blood vessel to ensure that integration of the cross-sectional flow would yield a total flow according to Appellants' claim, as discussed above. 3. Claims 1-5, 7, 9, 10-12, 16, and 17 Issue Appellants argue that the Examiner erred because the combined cited prior art references neither teach nor suggest the limitation of claim 1 reciting: "a) derive a total volume flow in said blood vessel; b) using imaging output of said medical imaging device, determine an amount of a contrast agent in a blood vessel; and c) based on the derived flow and the determined amount, normalize perfusion data." App. Br. 33. Analysis Appellants explain again their interpretation of the teachings of Bredno, and argue that Bredno does not disclose or suggest anything with regard to perfusion as that term is used in the instant claims. App. Br. 33. Appellants argue further that the Examiner does not specify how Bredno is being modified in view of Flohr. Id. Appellants essentially repeat their arguments with respect to the combined teachings of Bredno, Flohr, Waechter, and Yoganathan discussed supra with respect to claim 6. Appellants contend that it is unclear to them how the teachings of the various references are to be combined or how they teach the recited limitations of the claims. See, e.g., App. Br. 39-44. We find Appellants' arguments no more persuasive upon repetition, for the reasons explained supra. If anything, the limitations of claim 1 are 22 Appeal2017-002926 Application 14/004, 195 broader than claim 6, because claim 1 does not require: "wherein the amount of contrast agent is determined by determining an integrated volume of contrast agent flowing through a defined section of the blood vessel," but merely requires: "deriv[ing] a total volume flow in said blood vessel ... [and] determin[ing] an amount of a contrast agent in a blood vessel; and [] based on the derived flow and the determined amount, normalize perfusion data." We have explained supra why the combined teachings of Bredno, Waechter, and Yoganathan teach deriving a total volume flow and determining the amount of the contrast agent in the blood vessel, and how Flohr teaches the dynamic normalization of such data. We consequently affirmtheExaminer'srejectionofclaims 1-5, 7, 9, 10-12, 16, and 17. 4. Claims 18 and 23 Appellants argue that Kapoor does not cure the alleged deficiencies of the other references with respect to these claims. App. Br. 47--48. We have already explained why we do not find Appellants' arguments persuasive in that respect, and we affirm the Examiner's rejection of the claims. 5. Claims 19, 22, and 24 Issue Appellants argue that the Examiner erred because the combined cited prior art references neither teach nor suggest: "said placing being such that backflow of the injected contrast agent occurs in said blood vessel, the determining being based on flow through a cross-section of said blood vessel disposed beyond said backflow," as recited in claim 19. App. Br. 48. 23 Appeal2017-002926 Application 14/004, 195 Analysis Appellants present the same arguments with respect to claims 19, 22, and 24 as were presented with respect to claim 21. App. Br. 48--49. We have explained the reasons why we do not find Appellants' arguments persuasive and we incorporate by reference that explanation with respect to these claims. Appellants argue further, pointing to the Examiner's finding that: "The choice of the section of the [reference] blood vessel in front of the catheter tip is a matter of choice and engineering design to insure the precision of the measurement by avoiding turbulence during the measurements." App. Br. 49 (quoting Final Act. 18). According to Appellants, Flohr is the only reference that mentions the reference blood vessel, teaching that, in selecting the reference vessel: "it is obvious to select an artery led to the tissue." Id. (citing Flohr ,r 46). Appellants note that Flohr then states that: "The decision as to which type of vessel and which section of the vessel is intended to be used as a reference could for example be made by a medical practitioner depending on the examination region." Id. Appellants assert further that Flohr has no teaching or suggestion of turbulence, or of turbulence being relevant to the decision by the medical practitioner. App. Br. 49. Appellants contend that contrast measurement, for example, can occur in the midst ofbackflow. Id. Appellant are therefore unclear as to what, if any, proper source exists for the Examiner's finding. In the rejection at hand, the Examiner finds that van 't Hof teaches that the catheterization for angiographic assess of myocardial reperfusion for patient with primary angioplasty after acute infarction for performing 24 Appeal2017-002926 Application 14/004, 195 coronary angiogram with a contrast agent while checking of a "no-reflow" phenomenon or open epicardial artery without flow into the myocardial tissue. Id. at 48--49 (citing van 't Hof 2302). The Examiner finds that, to achieve that purpose, van 't Hof teaches that the injection of the contrast agent (Hexabrix) is performed until backflow into the aorta is observed to ensure the filling of the epicardial coronary artery with the adequate amount of contrast agent and to check for a no-reflow indicative of blood flow leakage. Id. ( citing van 't Hof 2303). We agree with the Examiner and incorporate by reference our explanation and conclusion set forth supra with respect to claim 21. We consequently affirm the Examiner's rejection with respect to claims 19, 22, and 24. DECISION The Examiner's rejection of claims 1-12 and 16-24 under 35 U.S.C. § 101 is reversed. The Examiner's rejection of claims 1-12 and 16-24 under 35 U.S.C. § 103(a) is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv). AFFIRMED 25 Copy with citationCopy as parenthetical citation