DETAILED ACTION
This office action is in response to the communication received on December 15, 2025 concerning application No. 18/044,867 filed on March 10, 2023.
Claims 1-17 are currently pending.
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 15, 2025 has been entered.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-17 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Information Disclosure Statement
The information disclosure statements filed 12/15/2025 and 01/20/2026 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Specifically, copies of the non-patent literature documents lists are not provided in the file wrapper.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 2, 4, 8-10, 12-13 and 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable by Dumoulin (US 20120253176) in view of Allen et al. (“Controlling Cavitation-Based Image Contrast in Focused Ultrasound Histotripsy Surgery”, hereinafter Allen).
Regarding claim 1, Dumoulin teaches a method of treating a patient with MR-guided histotripsy therapy ([0042] discloses MR imaging is used for MR-guided focused ultrasound treatment and thermal therapy. [0067] discloses the focused ultrasound is applied to cause cavitation, therefore the therapy is histotripsy therapy), comprising the steps of:
driving a hybrid electronic driver to emit ultrasound pulses below a cavitation threshold from a histotripsy therapy transducer ([0058] “in step 405 low-power focused ultrasound energy may be applied during the acquisition of images to test the location of the focal spot”);
identifying an ultrasound focal location of the histotripsy therapy transducer on a real-time MR image based on the emitted ultrasound pulses below the cavitation threshold ([0058] “the location of the focal spot is determined in step 406…using temperature-sensitive MR…the location of the focal spot may also be determined with acoustic radiation force imaging using MR”. [0041] discloses the MRI scanner is used to monitor the patient in real-time);
positioning the ultrasound focal location on a target tissue ([0059] discloses the focal spot is moved until it is at the desired location (target tissue));
driving the hybrid electronic driver to emit histotripsy pulses above the cavitation threshold into the target tissue to generate cavitation in the target tissue at the ultrasound focal location ([0060]-[0061] disclose at step 409 power is applied to the transducer at a level and for a period of time sufficient to have a therapeutic effect on the targeted tissue);
acquire real-time MR images of the target tissue to monitor cavitation in the target tissue ([0061] discloses at step 410 assessment of the temperature-sensitive images from the imaging scanner (MR images) is used to evaluate the efficacy of the treatment).
Dumoulin does not specifically teach transmitting histotripsy-synchronized displacement encoding gradients to induce random phases associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue.
However,
Allen in a similar field of endeavor teaches transmitting histotripsy-synchronized displacement encoding gradients to induce random phases associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue (pg. 5 “IVIM imaging” subsection discloses using intravoxel incoherent motion (IVIM) imaging which is a pulsed-gradient method for diffusion coefficient measurement. The use of an IVIM sequence induces random motions in the tissue that are captured in an IVIM image of the tissue. pgs. 205-206 “Histotripsy and IVIM imaging” further disclose “transmitting histotripsy-synchronized displacement encoding gradients to induce random phased associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue” and using “IVIM-encoding gradients”. Additionally, [0066] of the present applications specification discloses “IVIM pulse sequence used histotripsy-synchronized, displacement encoding gradients to induce random phases associated with random flow”, therefore by using an IVIM pulse sequence Allen discloses transmitting histotripsy-synchronized, displacement encoding gradients to induce random phases associated with random flow).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method disclosed by Dumoulin to transmit histotripsy-synchronized displacement encoding gradients to induce random phases associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue in order to improve the overall quality of the acquired MR image by providing a precise image of the cavitation process, as recognized by Allen (Introduction, pg. 204).
Regarding claim 2, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin further teaches identifying the ultrasound focal location comprises detecting the ultrasound energy with a MR-acoustic radiation force impulse (MR-ARFI) system ([0058] “the location of the focal spot may also be determined with acoustic radiation force imaging using MR”).
Regarding claim 4, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin further teaches identifying the ultrasound focal location comprises emitting ultrasound energy to create a 1-4 deg C temperature increase at the ultrasound focal location ([[0059] discloses raising the temperature of tissue less than 4 deg C during the determining focal spot step); and detecting the temperature increase with a MR thermometry system ([0063] disclose using MR thermal imaging or temperature mapping to identify the region of interest. Therefore the system used is an MR thermometry system).
Regarding claim 8, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Allen further teaches acquiring MR images of the target tissue further comprises acquiring MR images with an intravoxel incoherent motion (IVIM) imaging pulse sequence (pgs. 205-206 “IVIM imaging” and “Histotripsy and IVIM imaging” disclose using an IVIM imaging pulse sequence to acquire MR images).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method disclosed by Dumoulin in view of Allen to acquire MR images with an intravoxel incoherent motion (IVIM) imaging pulse sequence in order to improve the overall quality of the acquired MR image by providing a precise image of the cavitation process, as recognized by Allen (Introduction, pg. 204).
Regarding claim 9, Dumoulin in view of Allen teaches the method of claim 8, as set forth above. Allen further teaches the IVIM sequence comprises a spin-echo (SE) sequence (pg. 205, “IVIM imaging” discloses using “spin-echo sequences”. Fig. 1 additionally shows an obtained spin-echo image of the target).
Regarding claim 10, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin further teaches acquiring MR thermometry images of the target tissue to monitor heating of the target tissue ([0061] discloses at step 410 assessment of the temperature-sensitive images from the imaging scanner (MR thermometry images) is used to evaluate the efficacy of the treatment).
Regarding claim 12, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin further teaches acquiring post-treatment MR images to evaluate histotripsy ablation ([0061 discloses an evaluation step is performed after the target has been treated which entails assessing temperature sensitive images, therefore post-treatment MR images are acquired).
Regarding claim 13, Dumoulin in view of Allen teaches the method of claim 12, as set forth above. Dumoulin further teaches quantitatively assessing a level of tissue disruption generated by histotripsy with the post-treatment MR images ([0070] further discloses creating temperature different images of the region of interest that provide quantitative measure of tissue in response to the therapy).
Regarding claim 16, Dumoulin in view of Allen teaches the method of claim 13, as set forth above. Dumoulin further teaches the acquiring MR images step is synchronized with the transmitting histotripsy pulses step ([0041] discloses the medical instrument (ultrasonic device) is used on the patient while the patient is in the MRI scanner, therefore the acquiring of the MR images is synchronized with the transmitting of the histotripsy pulses).
Regarding claim 17, Dumoulin teaches an ultrasound system (the system 100 shown in fig. 1), comprising:
a magnetic resonance imaging (MRI) compatible histotripsy therapy transducer configured to transmit histotripsy pulses to an ultrasound focal location in a target tissue volume ([0051] medical device 103 is an ultrasonic ablation instrument for ablating tissue);
a MRI system configured to generate MR images of the target tissue volume within a magnetic field ([0048]-[0049] MRI scanner 102 is used for generating MR images;
a hybrid electronic driver coupled to the MRI compatible histotripsy therapy transducer and placed outside the magnetic field (imaging processing system 200 in fig. 1), the hybrid electronic driver being configured to, in a first driving mode, emit ultrasound energy below a cavitation threshold from the histotripsy therapy transducer ([0058] “in step 405 low-power focused ultrasound energy may be applied during the acquisition of images to test the location of the focal spot”), and in a second mode, emit histotripsy pulses above the cavitation threshold from the histotripsy therapy transducer into the target tissue to generate cavitation in the target tissue ([0060]-[0061] disclose at step 409 power is applied to the transducer at a level and for a period of time sufficient to have a therapeutic effect on the targeted tissue);
the MRI system being further configured to identify the ultrasound focal location of on a real-time MR image of the target tissue volume when the hybrid electronic driver drives the MRI compatible histotripsy therapy transducer below the cavitation threshold ([0058] “the location of the focal spot is determined in step 406…using temperature-sensitive MR…the location of the focal spot may also be determined with acoustic radiation force imaging using MR”. [0041] discloses the MRI scanner is used to monitor the patient in real-time), the MRI system being further configured to acquire real-time MR images of the target tissue to monitor cavitation resulting from the histotripsy pulses in the target tissue with pulse-sequences synchronized to histotripsy pulses when the hybrid electronic driver drives the MRI compatible histotripsy therapy transducer above the cavitation threshold ([0061] discloses at step 410 assessment of the temperature-sensitive images from the imaging scanner (MR images) is used to evaluate the efficacy of the treatment. [0041] further discloses the medical instrument (ultrasonic device) is used on the patient while the patient is in the MRI scanner, therefore the acquiring of the MR images is synchronized with the transmitting of the histotripsy pulses).
Dumoulin does not specifically teach the MRI system is further configured to transmit histotripsy-synchronized displacement encoding gradients to induce random phases associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue.
However,
Allen in a similar field of endeavor teaches transmitting histotripsy-synchronized displacement encoding gradients to induce random phases associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue (pg. 5 “IVIM imaging” subsection discloses using intravoxel incoherent motion (IVIM) imaging which is a pulsed-gradient method for diffusion coefficient measurement. The use of an IVIM sequence induces random motions in the tissue that are captured in an IVIM image of the tissue. pgs. 205-206 “Histotripsy and IVIM imaging” further disclose “transmitting histotripsy-synchronized displacement encoding gradients to induce random phased associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue” and using “IVIM-encoding gradients”. Additionally, [0066] of the present applications specification discloses “IVIM pulse sequence used histotripsy-synchronized, displacement encoding gradients to induce random phases associated with random flow”, therefore by using an IVIM pulse sequence Allen discloses transmitting histotripsy-synchronized, displacement encoding gradients to induce random phases associated with random flow).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the system disclosed by Dumoulin to transmit histotripsy-synchronized displacement encoding gradients to induce random phases associated with random flow in the target tissue to acquire real-time MR images of the random flow in the target tissue in order to improve the overall quality of the acquired MR image by providing a precise image of the cavitation process, as recognized by Allen (Introduction, pg. 204).
Claim(s) 3 and 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dumoulin and Allen as applied to claims 2 and 13 above and further in view of Partanen et al. (US 20170000376, hereinafter Partanen).
Regarding claim 3, Dumoulin in view of Allen teaches the method of claim 2, as set forth above.
Dumoulin in view of Allen does not specifically teach detecting the ultrasound energy with the MR-ARFI system comprises detecting displacement at the ultrasound focal location.
However,
Partanen in a similar field of endeavor teaches detecting the ultrasound energy with the MR-ARFI system comprises detecting displacement at the ultrasound focal location ([0112] discloses MR-ARFI is used to localize the focal point by “capturing HIFU-induced tissue displacement in the MR image”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the MR-ARFI system of Dumoulin in view of Allen for the MR-ARFI system of Partanen in order to allow for the predictable results of determining the focal location.
Regarding claim 14, Dumoulin in view of Allen teaches the method of claim 13, as set forth above. Dumoulin in view of Allen does not specifically teach applying diffusion weighted MRI.
However,
Partanen in a similar field of endeavor teaches applying diffusion weighted MRI ([0113] discloses the acquired MR data includes “diffusion-weighted images”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the MR scanning of Dumoulin in view of Allen for the diffusion weighted MRI of Partanen in order to allow for the predictable results of detecting the histotripsy induced cavitation.
Regarding claim 15, Dumoulin in view of Allen teaches the method of claim 13, as set forth above.
Dumoulin in view of Allen does not specifically teach applying MR elastography.
However,
Partanen in a similar field of endeavor teaches applying MR elastography ([0113] discloses the acquired MR data includes “magnetic resonance elastography (MRE)”. Also [0149]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the MR scanning of Dumoulin in view of Allen for the MR elastography of Partanen in order to allow for the predictable results of evaluating the histotripsy induced cavitation.
Claim(s) 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dumoulin and Allen as applied to claim 1 above and further in view of in view of Mei (US 20190320904).
Regarding claim 5, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin in view of Allen does not specifically teach the histotripsy pulses are transmitted through a skull of a patient.
However,
Mei in a similar field of endeavor teaches transmitting histotripsy pulses through a skull of a patient ([043] “the ultrasound energy transcranially delivered by the focused ultrasound system through the patient’s skull”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method disclosed by Dumoulin in view of Allen to have the histotripsy pulses be transmitted through a skull of a patient in order to non-invasively apply therapy to the target region.
Regarding claim 6, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin in view of Allen does not specifically teach the target tissue is in a brain of a patient.
However,
Mei in a similar field of endeavor teaches the target tissue is in a brain of a patient ([0043] discloses the thalamus in the patient’s brain is the target).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method disclosed by Dumoulin in view of Allen to have the target tissue be in a brain of a patient in order to increase the number of regions the system can be used to treat, thereby making the system more versatile.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dumoulin and Allen as applied to claim 1 above and further in view of Jang et al. (US 20200254285, hereinafter Jang).
Regarding claim 7, Dumoulin in view of Allen teaches the method of claim 1, as set forth above. Dumoulin in view of Allen does not specifically teach acquiring images further comprises acquiring images of bubble expansion and collapse events and not the cavitation itself.
However,
Jang in a similar field of endeavor teaches acquiring images comprises acquiring images of bubble expansion and collapse events and not the cavitation itself ([0030] discloses the bubble is imaged at a time of formation (expansion) of the bubble and a time of collapse of the bubble).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method disclosed by Dumoulin in view of Allen to have acquiring the images further comprises acquiring images of bubble expansion and collapse events and not the cavitation itself in order to be able to measure the efficacy of the therapy, as recognized by Jang ([0085]).
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dumoulin and Allen as applied to claim 1 above and further in view of Vahala (US 20150148659).
Regarding claim 11, Dumoulin in view of Allen teaches the method of claim 10, as set forth above. Dumoulin in view of Allen does not specifically teach acquiring MR thermometry images interleaved with acquiring MR images.
However,
Vahala in a similar field of endeavor teaches acquiring MR thermometry images interleaved with acquiring MR images ([0036] discloses acquiring the MR thermometry data and the MR morphological data (MR images) with an interleaved pulse sequence).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method disclosed by Dumoulin in view of Allen to have acquired MR thermometry images interleaved with acquiring MR images in order to provide high spatial resolution data to accurately measure the temperature distribution and resolution data, as recognized by Vahala ([0037]).
Conclusion
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/ANDREW W BEGEMAN/Examiner, Art Unit 3798