DETAILED ACTION
Continued Examination under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
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
Applicant’s response to the last Office Action, filed on 05/06/2025 has been entered and made of record.
Rejections of claim 13 under 35 USC 112(b) have been withdrawn. Remaining rejections are maintained, see analysis below.
Response to Arguments
Applicant's arguments filed on 05/06/2025 have been fully considered but they are not persuasive.
Regarding claim 1, the newly amended claims require injecting an area distant from the target area and circulating the thermally controlled fluid through the blood vessel via the heart, wherein the heart facilitates thermo-dilution of the thermally controlled fluid with blood while maintaining a thermal contrast between the thermally controlled fluid and the blood vessel. Examiner notes that Sultan teaches that its thermal digital subtraction angiography includes a pulmonary arterial angiography, see ¶ 0079-0080. This includes injection of a thermally controlled warm fluid into a vein or directly into the right ventricle in order to allow the thermally controlled fluid to flow from the heart into the lungs for pulmonary arterial angiography.
Applicant argues that the remaining independent claims are allowable for similar reasons and that the dependent claims are allowable by virtue of their dependence on allowable claims, but directs no independent arguments to these claims. Please see detailed response to arguments above.
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 14-16 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. The claims require acquiring an image of “the target area” without prior antecedent basis for this term. Appropriate correction is required.
Claims 14-15 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. The claims require acquiring the “the pre-contrast thermal image” in step “d.” after the thermal temperature change contrast event of step “c.” (cold and hot air in claims 15 and 16 respectively). Appropriate correction is required.
Allowable Subject Matter
Claims 5-7 and 9 are allowed.
The prior art of record, alone or in combination, fails to fairly teach or suggest these limitations, including the concept of a method for performing thermal digital subtraction angiography, method for performing thermal digital subtraction angiography, the method comprising: acquiring a pre-contrast thermal image of a target area; spraying an evaporative fluid onto the target area; acquiring a post-contrast thermal image after the evaporation of the evaporative fluid; acquiring a plurality of post-contrast thermal images after a fixed time interval; processing of the pre-contrast thermal image, the post-contrast thermal image and the plurality of post-contrast thermal images; assessing the heart rate for determining the core body temperature of the individual and generating a thermogram.
For example, Achilefu (US PGPub 2019/0328238) teaches a system for medical image enhancement via thermal stimulation of tissue (such as heating or cooling) to create a contrast enhancement and comparing post-contrast images with a pre-contrast reference image. The main embodiment teaches using a laser stimulation to heat and ¶ 0109 teaches that the thermal stimulation can also be accomplished via cooling. Achilefu teaches assessing the rate of change of a spatial temperature distribution as a function of time after introduction of the thermal stimulation. Achilefu ¶ 0073 teaches using the thermogram technique for skin cancer and skin lesion screening. Leschinsky (US PGPub 2014/0236020) likewise teaches a technique for thermographic assessment of tissue and teaches applying cooling to tissue by applying an evaporating fluid. Leschinsky ¶ 0001 and 0015 teach doing so for the purpose of assessing tissue viability, for example to aid in surgical decision making on whether to remove damaged tissue. Neither reference teaches or suggests using these techniques for an assessment of the heart rate for determining the core body temperature of the individual. Examiner finds that using these particular techniques of thermal imaging of an evaporative fluid for core body temperature measurement via heart rate assessment is significantly beyond the closest prior art here. The claim language goes beyond the similarities of these devices and Applicant’s invention and a combination could not reasonably be made without impermissible hindsight. The differences here are viewed as allowable over the prior art.
Claims 10-13 are allowed.
The prior art of record, alone or in combination, fails to fairly teach or suggest these limitations, including the concept of a method of performing digital subtraction angiography, the method comprising: acquiring a first pre-contrast thermal image of the target area; placing a thin plastic barrier over the target area; acquiring a second pre-contrast thermal image after the temperature recovery of the target area; spraying of an evaporative fluid over the barrier; acquiring a post-contrast thermal image after the evaporation of the evaporative fluid; processing of the first pre-contrast thermal image, the second pre-contrast thermal image and the post-contrast thermal image; and obtaining the thermographic data corresponding to a plurality of points of the target area generating a composite thermogram.
For example, Achilefu teaches a system for medical image enhancement via thermal stimulation of tissue (such as heating or cooling) to create a contrast enhancement and comparing post-contrast images with a pre-contrast reference image. The main embodiment teaches using a laser stimulation to heat but ¶ 0109 teaches that the thermal stimulation can also be performed via cooling. Achilefu teaches assessing the rate of change of a spatial temperature distribution as a function of time after introduction of the thermal stimulation. Achilefu ¶ 0073 teaches using the thermogram technique for skin cancer and skin lesion screening. Leschinsky likewise teaches a technique for thermographic assessment of tissue and teaches applying cooling to tissue by applying an evaporating fluid. Leschinsky ¶ 0001 and 0015 teach doing so for the purpose of assessing tissue viability, for example to aid in surgical decision making on whether to remove damaged tissue. Hunt (US PGPub 2021/0145359) teaches a system for wound tissue monitoring including using a number of sensors for assessing the state of a wound. For example, ¶ 0200 teaches temperature monitoring. ¶ 0092 and 0115 teach dressing the wound with a transparent plastic film layer. However, none of the references teach or suggest a method including acquiring a first pre-contrast thermal image, placing a thin plastic barrier, acquiring a second pre-contrast thermal image after the temperature recovery of the target area, spraying of an evaporative fluid over the barrier, acquiring a post-contrast thermal image after the evaporation of the evaporative fluid, processing the images and obtaining data to generate a composite thermogram. The concept of creating successive pre-contrast reference images one each before and after application of a plastic film and both before application of the evaporative fluid and then using the thermographic data to generate a composite thermogram is significantly beyond what the closest art of Achilefu and Leschinsky teach or suggest. The claim language goes beyond the similarities of these devices and Applicant’s invention and a combination could not reasonably be made without impermissible hindsight. The differences here are viewed as allowable over the prior art.
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.
Claim(s) 1, 2, and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over White (US PGPub 2007/0238954) in view of Sultan (US PGPub 2022/0156920) and Mohr (“Digital thermo-coronary angiography”).
Regarding claim 1, White discloses a method for performing digital subtraction angiography, the method comprising: (White teaches a system for medical image enhancement via injection of a contrast agent and comparing post-contrast images with a pre-contrast reference image, see ¶ 0003. Also, ¶ 0113 teaches blood vessel extraction/angiography via subtraction with the reference image.)
acquiring a pre-contrast image of a target area; (¶ 0093 and 0103 teach acquiring a ‘before’ image/pre-contrast reference image of a target area.)
injecting a fluid into a blood vessel at a speed an area distant from the target area at an area distant from the target area; (¶ 0103-0104 teach injecting a contrast agent after the ‘before’ image/pre-contrast image. Also see ¶ 0034. ¶ 0191-0193 teach injecting the agent at a speed of 50 µL per 5 seconds.)
acquiring a post-contrast image immediately after the injection of the fluid; (¶ 0046 and 0104-0105 teach acquiring ‘after’ images/post-contrast images, which includes the initial after image acquired immediately after the injection of the fluid that is shown at Fig. 1, numeral 104, labeled image “1” and discussed at ¶ 0105.)
acquiring a plurality of post-contrast images after a fixed time interval; (0104-0105 teach acquiring ‘after’ images/post-contrast images, which includes the images acquired subsequent to the initial image “1” in Fig. 1, numeral 103, labeled images “2” through “m”. ¶ 0159 and 0166 teach that these images are acquired successively at fixed specified time intervals.)
processing of the pre-contrast image, the post-contrast image and the plurality of post-contrast images; and (¶ 0113 and Fig. 1 teach processing that includes subtraction of the post-contrast image and the plurality of post-contrast images from the pre-contrast reference image.)
In the field of digital subtraction angiography Sultan teaches what White does not expressly disclose, namely, a technique for thermal digital subtraction angiography, that said images are thermal images, that said contrast agent is a thermally controlled fluid and generating a thermogram, and (Sultan teaches a technique for an enhanced thermal digital subtraction angiography. This includes injection of a thermally controlled warm fluid (¶ 0055) and imaging via an infrared thermal camera (¶ 0058). ¶ 0031 and 0065 teach subtraction of this image from a reference image that is created to exclude the warm fluid.)
injecting an area distant from the target area and circulating the thermally controlled fluid through the blood vessel via the heart, wherein the heart facilitates thermo-dilution of the thermally controlled fluid with blood while maintaining a thermal contrast between the thermally controlled fluid and the blood vessel. (Sultan teaches that its thermal digital subtraction angiography includes a pulmonary arterial angiography, see ¶ 0079-0080. This includes injection of a thermally controlled warm fluid into a vein or directly into the right ventricle in order to allow the thermally controlled fluid to flow from the heart into the lungs for pulmonary arterial angiography.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined White’s digital subtraction angiography with Sultan’s digital subtraction angiography. White teaches a system for medical image enhancement via injection of a contrast agent and comparing post-contrast images with a pre-contrast reference image. White does not expressly teach a detailed process for thermal imaging and injecting a thermal contrast agent. However, White ¶ 0039-0040 does teach that its process is generic to multiple contrast imaging modalities including thermography and that the type of contrast agent isn’t limited. ¶ 0104 expressly mentions using a temperature change as the contrast event. Sultan teaches a technique for a thermal digital subtraction angiography that includes injection of a thermally controlled warm fluid. The combination constitutes the repeatable and predictable result of simply applying Sultan’s teachings for using a thermally controlled fluid as the contrast agent, for the purpose of avoiding other contrast agents which may have toxicity and have higher expenses (Sultan ¶ 0009 and 0030). Simply using a thermal contrast agent cannot be considered a non-obvious improvement in view of the relevant prior art here. Using known engineering design, no “fundamental” operating principle of the teachings are changed; they continue to perform the same functions as originally taught prior to being combined.
In the field of digital thermal angiography Mohr teaches what the above combination does not expressly disclose, namely, injecting said thermally controlled fluid into a blood vessel at a speed ranging from 60 to 260 ml/min wherein the thermally controlled fluid has a temperature between 4o C to 47o C. (Mohr teaches thermal coronary angiography (TCA)-for real-time assessment of coronary anatomy and flow. Abstract teaches temperatures ranging from 10 to 40 degrees C and injection rates of 60-150 ml/min (1-2.5 ml/s).)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the above combination’s digital thermal angiography with Mohr’s digital thermal angiography. White teaches a system for medical image enhancement via injection including including thermography. Sultan teaches a technique for a thermal digital subtraction angiography that includes injection of a thermally controlled warm fluid. Sultan ¶ 0075 teaches the controlling the flow and temperature of the warm fluid but does not explicitly note the rate and temperature used. Mohr teaches thermal coronary angiography for real-time assessment of coronary anatomy and notes the flow rate and temperature. Simply injecting at a certain flow rate and temperature cannot be considered a non-obvious improvement in view of the relevant prior art here. Using known engineering design, no “fundamental” operating principle of the teachings are changed; they continue to perform the same functions as originally taught prior to being combined.
Regarding claim 2, the above combination discloses the method of claim 1 further comprises comparing and superimposing the post-contrast thermal image and the plurality of post-contrast thermal images with the pre-contrast thermal image; and (White ¶ 0032 teaches setting up an image difference overlay/superimposed image “to highlight differences in intensity between a reference image and a data image.” ¶ 0107-0108 teach superimposing the pre-contrast reference images with the post-contrast data set to perform a pixel-wise comparison of the images’ similarity, represented with their difference error. This includes the post-contrast image and the plurality of post-contrast images. The best superimposed image pair can thus be chosen.)
subtracting the superimposed portions of the post-contrast thermal image and the plurality of post-contrast thermal images with the pre-contrast thermal image. (As above, White ¶ 0107-0108 teach generating the superimposed image pairs. ¶ 0113 and Fig. 1 teach comparing via subtraction the pre-contrast reference images superimposed with the post-contrast image and the plurality of post-contrast images.)
Regarding claim 4, the above combination discloses the method of claim 1, wherein the IV fluid is ringer lactate, saline or dextrose solution and the temperature of the IV fluid is different from the normal body temperature. (Sultan ¶ 0032 teaches using intravenous fluid injectate that is ringer lactate or saline. ¶ 0035 teaches that the fluid is warmed above body temperature.)
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over White (US PGPub 2007/0238954) in view of Sultan (US PGPub 20220156920), Mohr (“Digital thermo-coronary angiography”) and Case (US PGPub 2016/0287088).
Regarding claim 3, the above combination discloses the method of claim 1, including analysing the thermogram for assessing the pathophysiological state of the subject or individual or assessing the heart rate for determining the core body temperature of the individual. (Sultan ¶ 0038 teaches using its thermogram technique for assessing in cases in which pathophysiological state may be acute chest pain secondary to pulmonary embolism.)
In the field of thermal angiography Case teaches determining a change in the rate of temperature recovery of the target area; and (Case teaches a technique for mapping vascular structures by selectively introducing heat into blood vessels relative to the surrounding tissue and using this thermal contrast to depict vascular structures, see Abstract. ¶ 0030-0034 teach determining a change in the rate of temperature recovery of the target area. ¶ 0070 teaches that these temperature changes are mapped in order to depict the blood vessels clearly.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the above combination’s thermal angiography with Case’s thermal angiography. Sultan teaches a technique for a thermal digital subtraction angiography that includes injection of a thermally controlled warm fluid for assessing vasculature circulation. Sultan does not describe details such as mapping changes in temperature recovery rate to generate the thermogram. Case teaches a technique for mapping vascular structures by selectively introducing heat into blood vessels to depict vascular structures and teaches determining a change in the rate of temperature recovery in order to depict the blood vessels clearly. The combination constitutes the repeatable and predictable result of simply applying Case’s teachings for using the change in temperature recovery rate as a tool in order to clearly depict the blood vessels in the thermogram (¶ 0070). Simply using this technique to generate a thermogram cannot be considered a non-obvious improvement in view of the relevant prior art here. Using known engineering design, no “fundamental” operating principle of the teachings are changed; they continue to perform the same functions as originally taught prior to being combined.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Achilefu (US PGPub 2019/0328238) in view of Leschinsky (US PGPub 2014/0236020).
Regarding claim 16, the above combination discloses a method for performing thermal digital subtraction angiography to identify microvascular health, the method comprising: (Achilefu teaches a system for medical image enhancement via thermal stimulation of tissue (such as heating or cooling) to create a contrast enhancement and comparing post-contrast images with a pre-contrast reference image, see Abstract and ¶ 0109. ¶ 0058 teaches subtraction for generating contrast with the reference image and ¶ 0064 teaches blood vessel segmentation/angiography. The main embodiment teaches using a laser stimulation to heat but ¶ 0109 teaches that the thermal stimulation can also be via cooling, since the temperature difference can be depicted with either.)
a. acquiring a pre-contrast thermal image of a target area; (¶ 0056 and Fig. 12, numeral 1202 teach thermal imaging to obtain a pre-contrast/baseline thermal image of the tissue.)
b. exposing the target area to temperature change ((¶ 0056 and Fig. 12, numeral 1204 teach applying thermal stimulation. ¶ 0055 teaches using a laser stimulation to heat and ¶ 0109 teaches that the thermal stimulation can also be via cooling. See the step of spraying evaporative fluid to cool the skin area.)
c. acquiring a post-contrast thermal image immediately after the temperature change at the target area; (¶ 0056 and Fig. 12, numeral 1206 teach thermal imaging to obtain a post-contrast thermal image of the tissue.)
d. acquiring a plurality of post-contrast thermal images after a fixed time interval; (¶ 0056 teaches that two or more additional thermal images may be obtained at 1206 at two or more time intervals.)
e. processing of the pre-contrast thermal image, the post-contrast thermal image and the plurality of post-contrast thermal images, and (¶ 0056 and Fig. 12, numeral 1208, 1210 and 1212 teach creating temperature plots, determining diffusion parameters and classifying tissue using the pre- and post-contrast thermal images.)
f. generating a thermogram. (¶ 0058 teaches that the thermal diffusion profile/ thermogram may be created at 1208 by pixel-wise subtraction of the pre-contrast images from the post-contrast images.)
In the field of thermal angiography Leschinsky teaches what Achilefu does not expressly disclose, namely, that said thermal stimulation includes spraying an evaporative fluid (Leschinsky teaches a technique for thermographic assessment of tissue viability by applying cooling to tissue and imaging the response, see Abstract. ¶ 0063 teaches that the source of a cooling stimulus is an evaporating fluid. ¶ 0081 teaches spraying liquid onto the tissue.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined Achilefu’s thermal angiography with Leschinsky’s thermal angiography. Achilefu teaches a system for medical image enhancement via thermal stimulation of tissue (such as heating or cooling) to create a contrast enhancement and comparing post-contrast images with a pre-contrast reference image. The main embodiment teaches using a laser stimulation to heat but ¶ 0109 teaches that the thermal stimulation can also be via cooling, since the temperature difference can be depicted with either. Leschinsky likewise teaches a technique for thermographic assessment of tissue and teaches applying cooling to tissue by applying an evaporating fluid. The combination constitutes the repeatable and predictable result of simply applying Leschinsky’s teachings for using an evaporative fluid for cooling, for the purpose of using cooling to apply the thermal stimulus in situations where cooling may be more tolerated by the patient, or to alternate heating/cooling cycles, as described at Leschinsky ¶ 0039. Simply using thermal cooling, especially when Achilefu already mentions this option, cannot be considered a non-obvious improvement in view of the relevant prior art here. Using known engineering design, no “fundamental” operating principle of the teachings are changed; they continue to perform the same functions as originally taught prior to being combined.
Conclusion
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/RAPHAEL SCHWARTZ/ Examiner, Art Unit 2671