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 .
Applicant' s arguments, 2/17/2026, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Applicants have amended their claims, filed 2/17/2026, and therefore rejections newly made in the instant office action have been necessitated by amendment.
Claims 1-21 are the pending with claims 1-4, 6-8, 10-13, 15-17, and 19-21 being under examination. Claims 5, 9, 14, and 18 have previously been withdrawn.
Claim Objections
Claim 3 is objected to because of the following informalities:
In claim 3, lines 1-2: “wherein the capturing the one or more first MRI images” is grammatically incorrect since it is missing the word “of” and should be: “wherein the capturing of the one or more first MRI images”.
Appropriate correction is required.
Claim Interpretation
The Office notes that amended claim 1 now recites that “each coil of the plurality of coils in the coil array is supplied with a different direct current” (lines 11-12). For clarity, under the broadest reasonable interpretation consistent with the specification, the term “different” is interpreted to mean that the plurality of coils are independently driven with respective DC currents from a first set of DC currents, such that at least some coils receive DC currents that differ from at least some other coils. The claim does not require that all coils receive mutually unique current magnitudes, nor does it require that every coil have a current value different from every other coil. The specification describes that “different coils in the shim array receive different DC currents 46, each having a predetermined magnitude” (Spec., ¶[0042]) and further explains that “[t]he set of DC currents generally includes different values for each coil in the array” (Spec., ¶[0050]). These passages support an interpretation in which the coils are independently supplied with DC currents determined on a per-coil basis, but do not require strict pairwise uniqueness of every current magnitude. Accordingly, the Office applies this broadest reasonable interpretation in evaluating the applied prior art. (Similarly recited in claims 10 and 19).
Additionally, for clarity, claim 1 recites “different” (line 19) which is interpreted under its broadest reasonable construction to include any change in current magnitudes, polarities, spatial weighting, or subset of driven coil elements between the first (labeling) and second (imaging) sets. (Similarly recited in claims 10 and 19).
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.
Claims 1-4, 7-8, 10-13, 16-17, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Stockmann et al. (Stockmann, Jason P, and Lawrence L Wald. “In Vivo B0 Field Shimming Methods for MRI at 7 T.” NeuroImage (Orlando, Fla.) 168 (2018): 71–87. Web.), hereto referred as Stockmann, and further in view of Zhao et al. (Zhao, Li et al. “Improving the Robustness of Pseudo‐continuous Arterial Spin Labeling to Off‐resonance and Pulsatile Flow Velocity.” Magnetic resonance in medicine 78.4 (2017): 1342–1351. Web.), hereto referred as Zhao, and further in view of Juchem et al. (Juchem, Christoph et al. “Multi-Coil Shimming of the Mouse Brain.” Magnetic resonance in medicine 66.3 (2011): 893–900), hereto referred as Juchem, and further in view of Helle et al. (Helle M, Norris DG, Rüfer S, Alfke K, Jansen O, van Osch MJ. Superselective Pseudocontinuous Arterial Spin Labeling. Magn Reson Med. 2010 Sep;64(3):777-86. doi: 10.1002/mrm.22451. PMID: 20597127.), hereto referred as Helle, and further in view of Hernandez-Garcia et al. (Hernandez-Garcia, Luis, Anish Lahiri, and Jonas Schollenberger. “Recent Progress in ASL.” NeuroImage (Orlando, Fla.) 187 (2019): 3–16. Web.), hereto referred as Hernandez-Garcia.
Regarding claim 1, Stockmann teaches that a method for perfusion magnetic resonant imaging (MRI) within an MRI system having at least one RF coil configured to transmit an RF signal (Stockmann, p. 10, Abstract: "We discuss and compare several promising hardware approaches for static and dynamic B0 shimming using either higher-order spherical harmonic shim coils or multi-coil shim arrays..."; Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil': "In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse...", showing that the method is implemented within an MRI system using advanced coil arrays and RF excitation pulses are transmitted by the system).
Stockmann does not explicitly teach that the method comprises providing a coil array configured for placement on a patient in the MRI system at a labeling plane that bisects a plurality of arteries. Rather, Stockmann describes a close-fitting coil array shaped to conform to the head of a subject during MRI, with the array used for both RF and shim functions (Stockmann, p. 12, 'Integrating B0 shim field generation into the RF receive coil': "A departure of the integrated ΔBO/Rx approach was to utilize the same close-fitting helmets used in RF arrays..."). It does depict bisection of arteries (Stockmann Figs. 1-2), which illustrate the positioning of the coil array relative to vascular anatomy, but does not explain or highlight that feature as part of the labeling configuration or imaging strategy. Zhao, who looks at spin labeling, identifies multiple positions used for pseudo-continuous arterial spin labeling, including one (L2) located above the carotid artery bifurcation and below the V3 segment, selected to encompass both the carotid and vertebral arteries (Zhao, p. 7, 'Volunteer Experiments and Evaluations': "Three locations were chosen based on the angiogram and inferior brain anatomy. As illustrated in Figure 3: L1: on the inferior border of the cerebellum (6); L2: above the carotid artery bifurcation and below the V3 segment..."). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the multi-coil shim array of Stockmann for use during the ASL labeling operation of Zhao such that the generated shim field modifies B0 conditions at the labeling plane selected in Zhao, because Zhao teaches the anatomical location of the labeling plane intersecting major feeding arteries and Stockmann teaches generating spatially controlled B0 fields in patient anatomy using a conformal multi-coil array (Zhao, p. 6, 'Volunteer Experiments and Evaluations': “All imaging was performed… using the body coil for transmission and an eight-channel head array for reception. PCASL was performed with repeated Hann RF pulses….”). Configuring Stockmann’s multi-coil shim array for use during Zhao’s ASL labeling operation would result in generation of a controlled B0 field at the labeling plane selected in Zhao, because Stockmann teaches spatially shaping B0 within a region of interest using a conformal coil array and Zhao teaches selection of a labeling plane intersecting the targeted arteries. The predictable result would be the ability to shape the magnetic field at the labeling plane location taught by Zhao. The benefit of the combination is a compact, anatomically conforming array (Stockmann) that enables effective arterial spin labeling across multiple targeted arteries (Zhao).
The combined Stockmann and Zhao does not fully teach capturing one or more first MRI images of the patient anatomy at a first imaging plane that is different from the labeling plane. Rather, the combined art shows acquisition of EPI and anatomical reference images across multiple imaging slices (Stockmann, p. 28, Fig. 5), supporting image quality assessment and shimming performance. It does not explicitly describe the relationship between those slices and any RF labeling plane. Zhao independently defines a labeling plane using anatomical landmarks (Zhao, p. 7, 'Volunteer Experiments'; Fig. 3), which is spatially distinct from the imaging slices used for capturing perfusion effects. The separate identification of the labeling plane and imaging plane is a core aspect of pseudo-continuous arterial spin labeling (PCASL). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have interpreted the combined Stockmann and Zhao's imaging slices as being distinct from Zhao's labeling plane, as this reflects standard ASL imaging configurations. The benefit of this combination is enhanced accuracy in perfusion quantification by enabling imaging at a site spatially separated from the RF tagging region, reducing interference and improving contrast reliability.
The combined Stockmann and Zhao does not fully teach applying a series of RF pulses to the at least one RF coil, to create an RF labeling field in the labeling plane. Rather, the combined art describes that RF pulses are transmitted by an RF coil of the MRI system while the shim array currents are applied concurrently. In particular, it notes that excitation pulses are coordinated with current application, beginning 500 µs before the RF event (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil': "In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse ..."). It does not describe the use of repeated RF pulses for arterial spin labeling. Zhao specifies that pseudo-continuous ASL was implemented using repeated Hann RF pulses, with each pulse lasting 500 us and separated by a 700 µs gap (Zhao, p. 6, 'Volunteer Experiments and Evaluations': "PCASL was performed with repeated Hann RF pulses.... RF duration was 500us and the gap between RFs was 700us."). Zhao illustrates a standard and clinically accepted PCASL configuration, including the timing, labeling geometry, and pulse pattern required for accurate perfusion labeling. This clearly discloses the type of repeated RF labeling structure required for generating the labeling field. Although Stockmann describes RF pulses and shim fields in the context of image acquisition, the structure and timing are compatible with ASL labeling sequences when combined with Zhao's pulse parameters. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann and Zhao to apply Zhao’s PCASL pulse train at the labeling plane while concurrently operating Stockmann’s independently driven multi-coil shim array, because Zhao teaches the RF labeling sequence and Stockmann teaches timed DC shim control relative to RF excitation events. The benefit of the combination is concurrent application of PCASL labeling RF pulses and tailored B0 conditions at the labeling plane for improved labeling robustness.
The combined Stockmann and Zhao does not fully teach applying a first set of direct currents to a plurality of coils in the coil array while the series of RF pulses are applied, each coil of the plurality of coils in the coil array being supplied with a different direct current such that a first resulting field in the labeling plane is a non-uniform magnetic field. Rather, the combined Stockmann and Zhao teaches a multi-coil (MC) shim array having independently driven channels with per-channel current control (Stockmann, p. 13, “In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse…”). Stockmann further teaches that “By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum” (Stockmann, p. 6), and that “Efforts toward further improvement by dynamically switching the SH shims on a slice-by-slice basis have also been pursued” (Stockmann, p. 8). Stockmann also demonstrates slice-optimized multi-coil shimming during RF operation (Stockmann, p. 34, Fig. 10; p. 35, Fig. 10). Thus, Stockmann shows per-channel hardware. However, the combined art does not expressly describe applying such independently controlled per-coil direct currents during a pseudo-continuous arterial spin labeling RF pulse train at a labeling plane.
Juchem explicitly teaches, during multi-coil shimming, loading “a single set of 48 individual current values” and that “[t]he corresponding currents were generated by 48 individual amplifiers”, which evidences supplying different DC current values across a plurality of coils/channels (Juchem , p. 4, 'Global and Slice-Specific Shimming of the Mouse Brain').
Zhao, as shown above, teaches applying a series of RF pulses at a defined labeling plane for pseudo-continuous arterial spin labeling (Zhao, p. 6–7). When Zhao’s labeling RF pulse train is applied at the labeling plane, and Stockmann’s independently driven per-coil direct currents are applied during RF operation as taught by Stockmann, the resulting field in the labeling plane would be non-uniform due to the spatially varying shim field produced by the different per-coil direct currents (Stockmann, p. 6; p. 8; p. 34, Fig. 10).
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Stockmann and Zhao in view of Juchem and Zhao to apply independently controlled, per-coil direct currents during Zhao’s PCASL labeling RF pulse sequence at the labeling plane, because Stockmann teaches hardware capable of independently driving shim currents on a per-channel basis and coordinating those currents temporally with RF excitation events, Zhao teaches applying a PCASL RF pulse train at a defined labeling plane, and Juchem expressly teaches implementing multi-coil shimming evidencing coil-specific current settings across a plurality of coils (as shown above). Combining these teachings would have involved applying the known per-channel current-setting methodology of Juchem to the multi-coil hardware platform of Stockmann while operating the known PCASL labeling sequence of Zhao, which represents the predictable use of prior art elements according to their established functions. The predictable result would be generation of a spatially tailored, non-uniform magnetic field at the labeling plane through different direct current values supplied to different coils of the array, enabling controlled manipulation of local B0 conditions during labeling. The benefit of the combination is improved control of magnetic field homogeneity and spatial selectivity at the labeling plane, which would enhance labeling efficiency and robustness in arterial spin labeling applications.
The combined Stockmann, Zhao, and Juchem does not fully teach that the RF labeling field labels a nuclear spin of blood in at least one artery of the plurality of arteries, while substantially not labeling the nuclear spin of blood in a remainder of the plurality of arteries. Rather, the combined art teaches that RF pulses are applied in temporal alignment with shim currents that alter the B0 field in space (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil'). While this enables magnetic field shaping during labeling, Stockmann does not disclose how this leads to selective labeling of one artery within a group. Helle teaches a modification to PCASL (Pseudo-Continuous Artery-Selective Spin Labeling) in which the RF pulse phase is adjusted in concert with additional gradient fields to ensure efficient inversion only at the center of a targeted artery, while surrounding vessels experience minimal labeling (Helle, Abstract; p. 778, 'MATERIALS AND METHODS': “This procedure leads to maximum labeling efficiency… The size of the labeling spot can be adjusted…”). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, and Juchem in view of Helle to apply Helle's spatially selective RF phase and gradient scheme during Stockmann's labeling sequence, because Stockmann's coil array provides the hardware and timing structure needed to support localized labeling based on B0 variation. The benefit of this combination is an MRI system capable of achieving precise, vessel-selective perfusion labeling using a single coil array that supports both RF transmission and programmable shim field generation.
The combined Stockmann, Zhao, Juchem, and Helle does not fully teach capturing one or more second MRI images of the patient anatomy at the first imaging plane after a perfusion delay while applying a second set of direct currents to the plurality of coils in the coil array, the second set of direct currents being different than the first set of direct currents. As shown in the combined art (Stockmann FIG. 9-10), dynamic shimming is performed during EPI acquisition corresponding to the imaging step, which reinforces that the shimming operation occurs concurrently with image capture, satisfying the temporal relationship of the imaging phase in the claim. The combined art also shows a pulse sequence that captures co-registered EPI slices at an imaging plane and further teaches dynamic shimming capability during acquisition (e.g., Stockmann, p. 6, Problems caused by static B0 inhomogeneity: "By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum", and p. 8, Dynamic spherical harmonic shimming: "Efforts toward further improvement by dynamically switching the SH shims on a slice-by-slice basis have also been pursued"), which provides the express means to apply a second (different) DC shim pattern during the imaging phase as compared to any DC pattern used during labeling. However, the combined art does not teach that the second set of direct currents is applied concurrently with acquisition of the second images at the first imaging plane after a perfusion delay in an ASL/PCASL context, nor that the second set is expressly defined as different from the first labeling-phase set, nor that these two sets are coordinated across distinct labeling and imaging planes linked by a PLD.
Zhao discloses a standard ASL/PCASL workflow in which (1) labeling is performed at a dedicated labeling plane using repeated RF pulses, (ii) labeling is followed by a post-labeling delay (PLD) (e.g.. 1.8 s) to allow tagged blood to traverse to the imaging slab, and (iii) images are then acquired at a first imaging plane that is different from the labeling plane (Zhao, p. 6-7, Volunteer Experiments and Evaluations; FIG. 3). Zhao further explains that labeling parameters were optimized for robustness and on-resonance inversion efficiency in the presence of off-resonance and pulsatile flow (e.g., B1, gradient waveform/ratio), and reports paired acquisitions comparing standard versus optimized (Optimal B1 and Gradient) labeling settings at the same location. Because Zhao performs labeling at a dedicated labeling plane, then waits a PLD (e.g., 1.8 s) and acquires images at a distinct imaging plane, the B0 objective at readout (distortion control in the imaging slab) is different from the B0 objective at labeling (on-resonance inversion at the labeling plane), motivating a different DC shim set during the second images. These teachings fill the gaps as follows: Zhao supplies the PLD requirement and the explicit separation of labeling and imaging planes, and establishes that labeling has different B0 demands (on-resonance at the labeling plane) than imaging (distortion control in the imaging slab). Consequently, when combined with Stockmann's dynamic slice-wise shimming at readout, Zhao's workflow and optimization guidance motivate using a second, different DC set during the second images than any DC set used during labeling, meeting the amended limitation. Moreover, Zhao's optimization of labeling parameters demonstrates the broader principle of parameter optimization across different sequence phases (labeling and imaging) providing direct motivation to separately tune DC shims for each phase, consistent with Stockmann's slice-by-slice optimization of B0 homogeneity during EPI acquisition. This combined approach would have been recognized by one of ordinary skill in the art as beneficial for maintaining field uniformity through temporal transitions from labeling to imaging to ensure accurate perfusion quantification.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined Stockmann, Zhao, Juchem, and Helle in view of Zhao by (i) performing PCASL labeling at the labeling plane with a first DC current set appropriate for labeling and then (ii) after the PLD, acquiring the second images at the imaging plane while concurrently applying a different, slice-optimized DC shim set during readout to reduce B0 inhomogeneity, thereby meeting the amended limitation. Under KSR, the tasks present a finite set of predictable choices (reuse the labeling DC pattern at readout vs. compute a slice-optimized imaging DC pattern); Stockmann teaches dynamic changes during acquisition and shows predictable improvement in slice homogeneity, yielding a reasonable expectation of success. Zhao (labeling) and Stockmann (imaging) each explicitly teach optimization for their respective tasks; adopting different DC sets for those distinct tasks would have been routine and expected. The benefit of the combination is twofold. Zhao provides improved labeling robustness by teaching optimized pseudo-continuous arterial spin labeling (PCASL) parameters that enhance on-resonance inversion efficiency and vessel selectivity at the labeling plane. Stockmann provides improved image quality by using dynamic, slice-specific B0 correction during acquisition of the second images, which reduces distortion and enhances signal-to-noise ratio. Together, the combined teachings yield predictable and complementary improvements in inversion efficiency, perfusion accuracy, and image fidelity across the respective labeling and imaging phases.
The combined Stockmann, Zhao, Juchem, and Helle does not fully teach comparing the one or more first MRI images and the one or more second MRI images to generate a map of perfusion associated with the at least one artery. Rather, the combined art demonstrates the use of EPI and anatomical images across imaging slices for evaluating the spatial uniformity of B0 shim performance (Stockmann, p. 34, Fig. 9). While this confirms image comparison is part of the system's diagnostic workflow, the combined art does not describe using label/control pairs or computing perfusion. Hernandez-Garcia, who investigates Arterial Spin Labeling, explicitly teaches the use of subtraction between control and labeled images to quantify the amount of blood entering tissue during an ASL labeling period, providing a direct method for generating perfusion maps (Hernandez-Garcia, p. 3, 'Introduction', FIG. 1). This process implicitly reflects perfusion through arterial pathways, such that the resulting maps represent blood flow associated with at least one artery contributing to the labeled region. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, and Helle in view of Hernandez-Garcia to apply image subtraction techniques to labeled and control ASL images to generate perfusion maps. The benefit of this combination is the integration of physiologic blood flow mapping with Stockmann's high-fidelity anatomical imaging and shim-optimized field performance.
Regarding claim 2, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not teach that the perfusion delay is 1–3 seconds after the applying the series of RF pulses. Rather, the combined art shows EPI image acquisition and pulse sequences for shimmed imaging using RF excitation but does not describe the inclusion of a perfusion delay following RF labeling (Stockmann, p. 29, Fig. 5). Zhao provides a detailed pseudo-continuous ASL protocol in which a 2-second labeling duration is followed by a 1.8-second post-labeling delay before image acquisition (Zhao, p. 6, 'Volunteer Experiments and Evaluations', ¶[1]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to implement a post-labeling delay between 1 and 3 seconds, because Zhao demonstrates this timing as standard for ASL perfusion imaging and Stockmann already provides the underlying imaging and shim hardware compatible with such timing structures. One of ordinary skill would have recognized that combining the well-established timing protocol from Zhao with Stockmann’s imaging system would enable accurate perfusion measurements without requiring any significant hardware changes. The benefit of the combination is a clinically validated timing sequence layered onto the precise image acquisition and shim control framework disclosed by Stockmann, resulting in a system capable of reliable and physiologically accurate perfusion imaging.
Regarding claim 3, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not explicitly teach that wherein the capturing the one or more first MRI images, the applying of the series of RF pulses, the applying of the first set of direct currents and the capturing of the one or more second images are repeated for a second imaging plane. Rather, the combined art discloses image acquisition across multiple slices (Stockmann, p. 28, Fig. 5), confirming that the imaging process is repeated for different anatomical planes, but does not clearly disclose that the labeling and acquisition process (including RF pulse train and direct currents) is repeated for each imaging plane in the context of perfusion imaging. Zhao describes an imaging sequence involving repeated application of labeling and image acquisition across a 3D volume composed of many slices (Zhao, p. 6, 'Volunteer Experiments and Evaluations', ¶[2]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to repeat the labeling and image acquisition steps for multiple imaging planes, because Zhao confirms that such repetition is standard for volumetric ASL imaging and Stockmann’s system is already capable of multi-slice acquisition. The benefit of the combination is the ability to generate perfusion maps across an extended volume of tissue using familiar and technically compatible imaging hardware.
Regarding claim 4, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia teaches that the coil array is a device placed on the head of the patient (Stockmann, p. 12, 'Integrating B0 shim field generation into the RF receive coil', ¶3: "A departure of the integrated ΔB0/Rx approach was to utilize the same close-fitting helmets used in RF arrays ..."; Stockmann describes a close-fitting coil array designed to be worn on the head of the subject, showing that the device is placed on the patient’s head).
Regarding claim 7, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia collectively teaches that the method comprises applying a second set of direct currents to the plurality of coils in the coil array, such that a second resulting field in the first imaging plane is a magnetic field that is more uniform than without the second set of direct currents.
Specifically, as shown above in claim 1, the combined art teaches labeling at a labeling plane, post-labeling delay (PLD), and acquisition of second images at a distinct imaging plane while applying a second, different set of direct currents. However, it does not specifically teach that the second magnetic field is more uniform than without the second set of direct currents.
The combined art teaches that applying slice-optimized multi-coil shim currents during EPI acquisition at the imaging plane reduces the standard deviation of ΔB0 within each slice, i.e., produces a more uniform B0 field than without those currents (Stockmann, p. 6, “By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum”; p. 34, Fig. 9 and p. 35, Fig. 10: “MC shimming reduces the standard deviation of ΔB0 in each slice, σB0 Local, by as much as 55%,” showing that applying slice-optimized shim currents, representing a second set of direct currents, results in improved uniformity of the magnetic field in the imaging plane; “Compared to global 1st–2nd shimming alone, the MC shim reduces the standard deviation in each slice … and brings the A-P and P-A phase encoded images into closer alignment,” confirming that the second, localized current configuration produces a more uniform magnetic field across the slice; This demonstrates that the second resulting field generated by the second set of direct currents during imaging is more uniform than without the second set).
In view of Zhao (Zhao, p. 6–7; FIG. 3) establishing the labeling-plane → PLD → imaging-plane sequence for the “second images” context of claim 1, it would have been obvious to apply the second, imaging-phase DC set as taught by Stockmann to improve B₀ uniformity during readout, thereby satisfying the added requirement that the second resulting field be more uniform than without the second DC set.
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to have the second resulting field in the first imaging plane be a magnetic field that is more uniform than without the second set of direct currents. The combination is technically feasible because both references operate in compatible MRI contexts using RF coils and controlled DC shim currents within standard pulse sequences. A person of ordinary skill would not need undue experimentation to implement Stockmann’s dynamic, slice-specific shimming during the imaging step of Zhao’s PCASL workflow. The motivation is that Stockmann demonstrates predictable improvement in B₀ homogeneity during readout, which directly complements Zhao’s perfusion labeling; the benefit is reduced distortion and improved SNR in the second images, yielding more accurate perfusion measurements.
Regarding claim 8, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not teach that the at least one artery includes a carotid artery. Rather, the combined art teaches the use of integrated RF and shim coil arrays for improving magnetic field uniformity during perfusion MRI. It demonstrates in vivo imaging using shimmed EPI slices in the brain but does not identify which arteries are labeled or mention the carotid artery (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil', ¶6). Zhao, on the other hand, explicitly defines labeling planes based on anatomical landmarks of the carotid artery, including its bifurcation, and Figure 3 shows that one of the labeling planes intersects the carotid arteries (Zhao, p. 16, Fig. 3; p. 7, 'Volunteer Experiments', ¶4; Fig. 3). This provides direct support for the inclusion of the carotid artery in the labeling field. One of ordinary skill in the art would have recognized that combining Stockmann’s field-shaping capabilities with Zhao’s anatomy-based labeling guidance would enable a more targeted and physiologically meaningful imaging setup. Since Stockmann already implements localized shim control in the brain, adapting the labeling position using Zhao’s established anatomical landmarks would have been a straightforward and logical integration of existing techniques. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to position the labeling plane such that it includes a carotid artery. The benefit of this combination is improved anatomical coverage of key cerebral inflow vessels, supporting more accurate and interpretable perfusion measurements without requiring structural changes to the imaging system.
Regarding claim 10, Stockmann teaches that a system for magnetic resonant imaging (MRI), the system comprising: at least one RF coil configured to transmit an RF signal (Stockmann, p. 10, Abstract: "We discuss and compare several promising hardware approaches for static and dynamic B0 shimming using either higher-order spherical harmonic shim coils or multi-coil shim arrays..."; Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil': "In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse...", showing that the method is implemented within an MRI system using advanced coil arrays and RF excitation pulses are transmitted by the system).
Stockmann does not explicitly teach that the system comprises a coil array configured for placement on a patient in an MRI imaging system at a labeling plane that bisects a plurality of arteries. Rather, Stockmann describes a close-fitting coil array shaped to conform to the head of a subject during MRI, with the array used for both RF and shim functions (Stockmann, p. 12, 'Integrating B0 shim field generation into the RF receive coil': "A departure of the integrated ΔBO/Rx approach was to utilize the same close-fitting helmets used in RF arrays..."). It does depict bisection of arteries (Stockmann Figs. 1-2), which illustrate the positioning of the coil array relative to vascular anatomy, but does not explain or highlight that feature as part of the labeling configuration or imaging strategy. Zhao, who looks at spin labeling, identifies multiple positions used for pseudo-continuous arterial spin labeling, including one (L2) located above the carotid artery bifurcation and below the V3 segment, selected to encompass both the carotid and vertebral arteries (Zhao, p. 7, 'Volunteer Experiments and Evaluations': "Three locations were chosen based on the angiogram and inferior brain anatomy. As illustrated in Figure 3: L1: on the inferior border of the cerebellum (6); L2: above the carotid artery bifurcation and below the V3 segment..."). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the multi-coil shim array of Stockmann for use during the ASL labeling operation of Zhao such that the generated shim field modifies B0 conditions at the labeling plane selected in Zhao, because Zhao teaches the anatomical location of the labeling plane intersecting major feeding arteries and Stockmann teaches generating spatially controlled B0 fields in patient anatomy using a conformal multi-coil array (Zhao, p. 6, 'Volunteer Experiments and Evaluations': “All imaging was performed… using the body coil for transmission and an eight-channel head array for reception. PCASL was performed with repeated Hann RF pulses….”). Configuring Stockmann’s multi-coil shim array for use during Zhao’s ASL labeling operation would result in generation of a controlled B0 field at the labeling plane selected in Zhao, because Stockmann teaches spatially shaping B0 within a region of interest using a conformal coil array and Zhao teaches selection of a labeling plane intersecting the targeted arteries. The predictable result would be the ability to shape the magnetic field at the labeling plane location taught by Zhao. The benefit of the combination is a compact, anatomically conforming array (Stockmann) that enables effective arterial spin labeling across multiple targeted arteries (Zhao).
The combined Stockmann and Zhao does not fully teach that the system comprises a computer configured to capture one or more first MRI images of patient anatomy at a first imaging plane that is different from the labeling plane. Rather, the combined art shows acquisition of EPI and anatomical reference images across multiple imaging slices (Stockmann, p. 28, Fig. 5), supporting image quality assessment and shimming performance. It does not explicitly describe the relationship between those slices and any RF labeling plane. Zhao independently defines a labeling plane using anatomical landmarks (Zhao, p. 7, 'Volunteer Experiments'; Fig. 3), which is spatially distinct from the imaging slices used for capturing perfusion effects. The separate identification of the labeling plane and imaging plane is a core aspect of pseudo-continuous arterial spin labeling (PCASL). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have interpreted the combined Stockmann and Zhao's imaging slices as being distinct from Zhao's labeling plane, as this reflects standard ASL imaging configurations, which implicitly uses a computer. The benefit of this combination is enhanced accuracy in perfusion quantification by enabling imaging at a site spatially separated from the RF tagging region, reducing interference and improving contrast reliability.
The combined Stockmann and Zhao does not fully teach that the system comprises a computer configured to apply a series of RF pulses to the at least one RF coil, to create an RF labeling field in the labeling plane. Rather, the combined art describes that RF pulses are transmitted by an RF coil of the MRI system while the shim array currents are applied concurrently. In particular, it notes that excitation pulses are coordinated with current application, beginning 500 µs before the RF event (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil': "In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse ..."). It does not describe the use of repeated RF pulses for arterial spin labeling. Zhao specifies that pseudo-continuous ASL was implemented using repeated Hann RF pulses, with each pulse lasting 500 us and separated by a 700 µs gap (Zhao, p. 6, 'Volunteer Experiments and Evaluations': "PCASL was performed with repeated Hann RF pulses.... RF duration was 500us and the gap between RFs was 700us."). Zhao illustrates a standard and clinically accepted PCASL configuration, including the timing, labeling geometry, and pulse pattern required for accurate perfusion labeling. This clearly discloses the type of repeated RF labeling structure required for generating the labeling field. Although Stockmann describes RF pulses and shim fields in the context of image acquisition, the structure and timing are compatible with ASL labeling sequences when combined with Zhao's pulse parameters. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann and Zhao to apply Zhao’s PCASL pulse train at the labeling plane while concurrently operating Stockmann’s independently driven multi-coil shim array, because Zhao teaches the RF labeling sequence and Stockmann teaches timed DC shim control relative to RF excitation events. The benefit of the combination is concurrent application of PCASL labeling RF pulses and tailored B0 conditions at the labeling plane for improved labeling robustness.
The combined Stockmann and Zhao does not fully teach that the system comprises a computer configured to apply a first set of direct currents to a plurality of coils in the coil array while the series of RF pulses are applied, each coil of the plurality of coils in the coil array being supplied with a different direct current of the first set of direct currents such that a first resulting field in the labeling plane is a non-uniform magnetic field. Rather, the combined Stockmann and Zhao teaches a multi-coil (MC) shim array having independently driven channels with per-channel current control (Stockmann, p. 13, “In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse…”). Stockmann further teaches that “By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum” (Stockmann, p. 6), and that “Efforts toward further improvement by dynamically switching the SH shims on a slice-by-slice basis have also been pursued” (Stockmann, p. 8). Stockmann also demonstrates slice-optimized multi-coil shimming during RF operation (Stockmann, p. 34, Fig. 10; p. 35, Fig. 10). Thus, Stockmann shows per-channel hardware. However, the combined art does not expressly describe applying such independently controlled per-coil direct currents during a pseudo-continuous arterial spin labeling RF pulse train at a labeling plane.
Juchem explicitly teaches, during multi-coil shimming, loading “a single set of 48 individual current values” and that “[t]he corresponding currents were generated by 48 individual amplifiers”, which evidences supplying different DC current values across a plurality of coils/channels (Juchem , p. 4, 'Global and Slice-Specific Shimming of the Mouse Brain').
Zhao, as shown above, teaches applying a series of RF pulses at a defined labeling plane for pseudo-continuous arterial spin labeling (Zhao, p. 6–7). When Zhao’s labeling RF pulse train is applied at the labeling plane, and Stockmann’s independently driven per-coil direct currents are applied during RF operation as taught by Stockmann, the resulting field in the labeling plane would be non-uniform due to the spatially varying shim field produced by the different per-coil direct currents (Stockmann, p. 6; p. 8; p. 34, Fig. 10).
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Stockmann and Zhao in view of Juchem and Zhao to apply independently controlled, per-coil direct currents during Zhao’s PCASL labeling RF pulse sequence at the labeling plane, because Stockmann teaches hardware capable of independently driving shim currents on a per-channel basis and coordinating those currents temporally with RF excitation events, Zhao teaches applying a PCASL RF pulse train at a defined labeling plane, and Juchem expressly teaches implementing multi-coil shimming evidencing coil-specific current settings across a plurality of coils (as shown above). Combining these teachings would have involved applying the known per-channel current-setting methodology of Juchem to the multi-coil hardware platform of Stockmann while operating the known PCASL labeling sequence of Zhao, which represents the predictable use of prior art elements according to their established functions. The predictable result would be generation of a spatially tailored, non-uniform magnetic field at the labeling plane through different direct current values supplied to different coils of the array, enabling controlled manipulation of local B0 conditions during labeling. The benefit of the combination is improved control of magnetic field homogeneity and spatial selectivity at the labeling plane, which would enhance labeling efficiency and robustness in arterial spin labeling applications.
The combined Stockmann, Zhao, and Juchem does not teach that the RF labeling field labels a nuclear spin of blood in at least one artery of the plurality of arteries, while substantially not labeling the nuclear spin of blood in a remainder of the plurality of arteries. Rather, the combined art teaches that RF pulses are applied in temporal alignment with shim currents that alter the B0 field in space (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil'). While this enables magnetic field shaping during labeling, Stockmann does not disclose how this leads to selective labeling of one artery within a group. Helle teaches a modification to PCASL (Pseudo-Continuous Artery-Selective Spin Labeling) in which the RF pulse phase is adjusted in concert with additional gradient fields to ensure efficient inversion only at the center of a targeted artery, while surrounding vessels experience minimal labeling (Helle, Abstract; p. 778, 'MATERIALS AND METHODS': “This procedure leads to maximum labeling efficiency… The size of the labeling spot can be adjusted…”). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, and Juchem in view of Helle to apply Helle's spatially selective RF phase and gradient scheme during Stockmann's labeling sequence, because Stockmann's coil array provides the hardware and timing structure needed to support localized labeling based on B0 variation. The benefit of this combination is an MRI system capable of achieving precise, vessel-selective perfusion labeling using a single coil array that supports both RF transmission and programmable shim field generation.
The combined Stockmann, Zhao, Juchem, and Helle does not fully teach that the system comprises a computer configured to capture one or more second MRI images of the patient anatomy at the first imaging plane after a perfusion delay while applying a second set of direct currents to the plurality of coils in the coil array, the second set of direct currents being different than the first set of direct currents. As shown in the combined art (Stockmann FIG. 9-10), dynamic shimming is performed during EPI acquisition corresponding to the imaging step, which reinforces that the shimming operation occurs concurrently with image capture, satisfying the temporal relationship of the imaging phase in the claim. The combined art also shows a pulse sequence that captures co-registered EPI slices at an imaging plane and further teaches dynamic shimming capability during acquisition (e.g., Stockmann, p. 6, Problems caused by static B0 inhomogeneity: "By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum", and p. 8, Dynamic spherical harmonic shimming: "Efforts toward further improvement by dynamically switching the SH shims on a slice-by-slice basis have also been pursued"), which provides the express means to apply a second (different) DC shim pattern during the imaging phase as compared to any DC pattern used during labeling. However, the combined art does not teach that the second set of direct currents is applied concurrently with acquisition of the second images at the first imaging plane after a perfusion delay in an ASL/PCASL context, nor that the second set is expressly defined as different from the first labeling-phase set, nor that these two sets are coordinated across distinct labeling and imaging planes linked by a PLD.
Zhao discloses a standard ASL/PCASL workflow in which (1) labeling is performed at a dedicated labeling plane using repeated RF pulses, (ii) labeling is followed by a post-labeling delay (PLD) (e.g.. 1.8 s) to allow tagged blood to traverse to the imaging slab, and (iii) images are then acquired at a first imaging plane that is different from the labeling plane (Zhao, p. 6-7, Volunteer Experiments and Evaluations; FIG. 3). Zhao further explains that labeling parameters were optimized for robustness and on-resonance inversion efficiency in the presence of off-resonance and pulsatile flow (e.g., B1, gradient waveform/ratio), and reports paired acquisitions comparing standard versus optimized (Optimal B1 and Gradient) labeling settings at the same location. Because Zhao performs labeling at a dedicated labeling plane, then waits a PLD (e.g., 1.8 s) and acquires images at a distinct imaging plane, the B0 objective at readout (distortion control in the imaging slab) is different from the B0 objective at labeling (on-resonance inversion at the labeling plane), motivating a different DC shim set during the second images. These teachings fill the gaps as follows: Zhao supplies the PLD requirement and the explicit separation of labeling and imaging planes, and establishes that labeling has different B0 demands (on-resonance at the labeling plane) than imaging (distortion control in the imaging slab). Consequently, when combined with Stockmann's dynamic slice-wise shimming at readout, Zhao's workflow and optimization guidance motivate using a second, different DC set during the second images than any DC set used during labeling, meeting the amended limitation. Moreover, Zhao's optimization of labeling parameters demonstrates the broader principle of parameter optimization across different sequence phases (labeling and imaging) providing direct motivation to separately tune DC shims for each phase, consistent with Stockmann's slice-by-slice optimization of B0 homogeneity during EPI acquisition. This combined approach would have been recognized by one of ordinary skill in the art as beneficial for maintaining field uniformity through temporal transitions from labeling to imaging to ensure accurate perfusion quantification.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined Stockmann, Zhao, Juchem, and Helle in view of Zhao by (i) performing PCASL labeling at the labeling plane with a first DC current set appropriate for labeling and then (ii) after the PLD, acquiring the second images at the imaging plane while concurrently applying a different, slice-optimized DC shim set during readout to reduce B0 inhomogeneity, thereby meeting the amended limitation. Under KSR, the tasks present a finite set of predictable choices (reuse the labeling DC pattern at readout vs. compute a slice-optimized imaging DC pattern); Stockmann teaches dynamic changes during acquisition and shows predictable improvement in slice homogeneity, yielding a reasonable expectation of success, all of which implicitly uses a computer. Zhao (labeling) and Stockmann (imaging) each explicitly teach optimization for their respective tasks; adopting different DC sets for those distinct tasks would have been routine and expected. The benefit of the combination is twofold. Zhao provides improved labeling robustness by teaching optimized pseudo-continuous arterial spin labeling (PCASL) parameters that enhance on-resonance inversion efficiency and vessel selectivity at the labeling plane. Stockmann provides improved image quality by using dynamic, slice-specific B0 correction during acquisition of the second images, which reduces distortion and enhances signal-to-noise ratio. Together, the combined teachings yield predictable and complementary improvements in inversion efficiency, perfusion accuracy, and image fidelity across the respective labeling and imaging phases.
The combined Stockmann, Zhao, Juchem, and Helle does not fully teach that the system comprises a computer configured to compare the one or more first MRI images and the one or more second MRI images to generate a map of perfusion associated with the at least one artery. Rather, the combined art demonstrates the use of EPI and anatomical images across imaging slices for evaluating the spatial uniformity of B0 shim performance (Stockmann, p. 34, Fig. 9). While this confirms image comparison is part of the system's diagnostic workflow, the combined art does not describe using label/control pairs or computing perfusion. Hernandez-Garcia, who investigates Arterial Spin Labeling, explicitly teaches the use of subtraction between control and labeled images to quantify the amount of blood entering tissue during an ASL labeling period, providing a direct method for generating perfusion maps (Hernandez-Garcia, p. 3, 'Introduction', FIG. 1). This process implicitly reflects perfusion through arterial pathways, such that the resulting maps represent blood flow associated with at least one artery contributing to the labeled region. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, and Helle in view of Hernandez-Garcia to apply image subtraction techniques to labeled and control ASL images to generate perfusion maps. The benefit of this combination is the integration of physiologic blood flow mapping with Stockmann's high-fidelity anatomical imaging and shim-optimized field performance.
Regarding claim 11, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not teach that the perfusion delay is 1–3 seconds after the series of RF pulses are applied. Rather, the combined art shows EPI image acquisition and pulse sequences for shimmed imaging using RF excitation but does not describe the inclusion of a perfusion delay following RF labeling (Stockmann, p. 29, Fig. 5). Zhao provides a detailed pseudo-continuous ASL protocol in which a 2-second labeling duration is followed by a 1.8-second post-labeling delay before image acquisition (Zhao, p. 6, 'Volunteer Experiments and Evaluations', ¶[1]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to implement a post-labeling delay between 1 and 3 seconds, because Zhao demonstrates this timing as standard for ASL perfusion imaging and Stockmann already provides the underlying imaging and shim hardware compatible with such timing structures. One of ordinary skill would have recognized that combining the well-established timing protocol from Zhao with Stockmann’s imaging system would enable accurate perfusion measurements without requiring any significant hardware changes. The benefit of the combination is a clinically validated timing sequence layered onto the precise image acquisition and shim control framework disclosed by Stockmann, resulting in a system capable of reliable and physiologically accurate perfusion imaging.
Regarding claim 12, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not explicitly teach that the computer is further configured to repeat the capturing of the one or more first MRI images, the applying of the series of RF pulses, the applying of the first set of direct currents and the capturing of the one or more second MRI images for a second imaging plane. Rather, the combined art discloses image acquisition across multiple slices (Stockmann, p. 28, Fig. 5), confirming that the imaging process is repeated for different anatomical planes, but does not clearly disclose that the labeling and acquisition process (including RF pulse train and direct currents) is repeated for each imaging plane in the context of perfusion imaging, nor that a computer is configured to coordinate this repetition. Zhao describes an imaging sequence involving repeated application of labeling and image acquisition across a 3D volume composed of many slices (Zhao, p. 6, 'Volunteer Experiments and Evaluations', ¶[2]), and such a protocol necessarily requires computer control, including the repeated application of direct currents for each imaging plane, as described above. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to repeat the labeling and image acquisition steps for multiple imaging planes using computer coordination, because Zhao confirms that such repetition is standard for volumetric ASL imaging and Stockmann’s system is already capable of multi-slice acquisition. The benefit of the combination is the ability to generate perfusion maps across an extended volume of tissue using familiar and technically compatible imaging hardware under automated system control.
Regarding claim 13, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia teaches that the system comprises a coil array that is a device placed on the head of the patient (Stockmann, p. 12, 'Integrating B0 shim field generation into the RF receive coil', ¶3: "A departure of the integrated ΔB0/Rx approach was to utilize the same close-fitting helmets used in RF arrays ..."; Stockmann describes a close-fitting coil array designed to be worn on the head of the subject, showing that the device is placed on the patient’s head).
Regarding claim 16, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia mostly teaches that applying a second set of direct currents to the plurality of coils in the coil array, such that a second resulting field in the first imaging plane is a magnetic field that is more uniform than without the second set of direct currents.
Specifically, as shown above in claim 10, the combined art teaches labeling at a labeling plane, post-labeling delay (PLD), and acquisition of second images at a distinct imaging plane while applying a second, different set of direct currents. However, it does not specifically teach that the second magnetic field is more uniform than without the second set of direct currents.
The combined art teaches that applying slice-optimized multi-coil shim currents during EPI acquisition at the imaging plane reduces the standard deviation of ΔB0 within each slice, i.e., produces a more uniform B0 field than without those currents (Stockmann, p. 6, “By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum”; p. 34, Fig. 9 and p. 35, Fig. 10: “MC shimming reduces the standard deviation of ΔB0 in each slice, σB0 Local, by as much as 55%,” showing that applying slice-optimized shim currents, representing a second set of direct currents, results in improved uniformity of the magnetic field in the imaging plane; “Compared to global 1st–2nd shimming alone, the MC shim reduces the standard deviation in each slice … and brings the A-P and P-A phase encoded images into closer alignment,” confirming that the second, localized current configuration produces a more uniform magnetic field across the slice; This demonstrates that the second resulting field generated by the second set of direct currents during imaging is more uniform than without the second set).
In view of Zhao (Zhao, p. 6–7; FIG. 3) establishing the labeling-plane → PLD → imaging-plane sequence for the “second images” context of claim 1, it would have been obvious to apply the second, imaging-phase DC set as taught by Stockmann to improve B₀ uniformity during readout, thereby satisfying the added requirement that the second resulting field be more uniform than without the second DC set.
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Zhao to have the second resulting field in the first imaging plane be a magnetic field that is more uniform than without the second set of direct currents. The combination is technically feasible because both references operate in compatible MRI contexts using RF coils and controlled DC shim currents within standard pulse sequences. A person of ordinary skill would not need undue experimentation to implement Stockmann’s dynamic, slice-specific shimming during the imaging step of Zhao’s PCASL workflow. The motivation is that Stockmann demonstrates predictable improvement in B₀ homogeneity during readout, which directly complements Zhao’s perfusion labeling; the benefit is reduced distortion and improved SNR in the second images, yielding more accurate perfusion measurements.
Regarding claim 17, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not explicitly teach that the system comprises a computer configured such that the at least one artery includes a carotid artery. Rather, the combined art teaches the use of integrated RF and shim coil arrays for improving magnetic field uniformity during perfusion MRI. It demonstrates in vivo imaging using shimmed EPI slices in the brain but does not identify which arteries are labeled or mention the carotid artery (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil', ¶6). Zhao, on the other hand, explicitly defines labeling planes based on anatomical landmarks of the carotid artery, including its bifurcation, and Figure 3 shows that one of the labeling planes intersects the carotid arteries (Zhao, p. 16, Fig. 3; p. 7, 'Volunteer Experiments', ¶4; Fig. 3). This provides direct support for the inclusion of the carotid artery in the labeling field. One of ordinary skill in the art would have recognized that combining the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia’s field-shaping capabilities with Zhao’s anatomy-based labeling guidance would enable a more targeted and physiologically meaningful imaging setup. Since Stockmann already implements localized shim control in the brain, adapting the labeling position using Zhao’s established anatomical landmarks would have been a straightforward and logical integration of existing techniques.
Regarding claim 21, the combined Stockmann, Zhao, Juchem, and Helle does not explicitly teach pausing the first set of direct currents while a main body coil of the MRI system applies background field suppression pulses. Rather, the art teaches time coordination of applied direct currents relative to RF excitation events (Stockmann, p. 13, “In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse…”). However, it does not teach pausing the first set of direct currents while a main body coil of the MRI system applies background field suppression pulses, that is, temporarily discontinuing the application of the first set of direct currents during the interval in which the background field suppression pulses are applied.
Zhao teaches the missing timing context by expressly teaching that background suppression is interleaved with labeling in the PCASL sequence, stating: “Interleaved labeling and background suppression was used…” (Zhao, p. 6, 'Volunteer Experiments and Evaluations'). Thus, Zhao teaches that background field suppression pulses occur as a defined portion of the PCASL pulse program, providing an identifiable interval during which the first set of direct currents can be paused using Stockmann’s taught timing control of current application relative to RF events (Stockmann, p. 13).
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Stockmann, Zhao, Juchem, and Helle in view of Zhao to pause the first set of direct currents during the background field suppression pulses, because Stockmann teaches that the direct currents are computer-controlled and time-coordinated relative to RF events (Stockmann, p. 13) and Zhao teaches inclusion of background suppression pulses in the PCASL sequence timing (Zhao, p. 6). Combining these teachings would have involved using Stockmann’s existing timing control over direct current application to temporarily discontinue the direct currents during the known background suppression pulse intervals in Zhao’s sequence, which represents the predictable use of prior art timing control according to its established function. The predictable result would be that background suppression pulses are applied without contemporaneous direct current application, while still permitting application of the first set of direct currents during other portions of the PCASL sequence. The benefit of the combination is improved robustness of the ASL acquisition by avoiding interference between background suppression pulses and applied direct currents.
Claims 6 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Stockmann et al. (Stockmann, Jason P, and Lawrence L Wald. “In Vivo B0 Field Shimming Methods for MRI at 7 T.” NeuroImage (Orlando, Fla.) 168 (2018): 71–87. Web.), hereto referred as Stockmann, and further in view of Zhao et al. (Zhao, Li et al. “Improving the Robustness of Pseudo‐continuous Arterial Spin Labeling to Off‐resonance and Pulsatile Flow Velocity.” Magnetic resonance in medicine 78.4 (2017): 1342–1351. Web.), hereto referred as Zhao, and further in view of Juchem et al. (Juchem, Christoph et al. “Multi-Coil Shimming of the Mouse Brain.” Magnetic resonance in medicine 66.3 (2011): 893–900), hereto referred as Juchem, and further in view of Helle et al. (Helle M, Norris DG, Rüfer S, Alfke K, Jansen O, van Osch MJ. Superselective pseudocontinuous arterial spin labeling. Magn Reson Med. 2010 Sep;64(3):777-86. doi: 10.1002/mrm.22451. PMID: 20597127.), hereto referred as Helle, and further in view of Hernandez-Garcia et al. (Hernandez-Garcia, Luis, Anish Lahiri, and Jonas Schollenberger. “Recent Progress in ASL.” NeuroImage (Orlando, Fla.) 187 (2019): 3–16. Web.), hereto referred as Hernandez-Garcia, and further in view of Jahanian et al. (Jahanian H, Noll DC, Hernandez-Garcia L. B0 field inhomogeneity considerations in pseudo-continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy. NMR Biomed. 2011 Dec;24(10):1202-9. doi: 10.1002/nbm.1675. Epub 2011 Mar 8. PMID: 21387447), hereto referred as Jahanian.
The combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia teaches claims 1 and 10 as described above.
Regarding claim 6, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not explicitly teach that the non-uniform magnetic field includes one or more regions where nuclear spins are at least 100 Hz off-resonance of the RF labeling field at a location of the remainder of the plurality of arteries. Rather, the combined art discloses the use of direct currents during the RF excitation pulse to shape a magnetic field in the labeling region (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil', ¶5). It does not specify that the resulting magnetic field includes one or more regions that shift the nuclear spins by at least 100 Hz off-resonance from the RF labeling field or where these shifts occur in relation to other arteries. Jahanian reports measured off-resonance values across multiple arteries in human subjects, including the left vertebral (LV), right vertebral (RV), left carotid (LC), and right carotid (RC) arteries. Table 2 shows that several of these arteries experience frequency shifts greater than ±100 Hz at the tagging plane (Jahanian, p. 1207, Table 2, 'In vivo results'). Moreover, Jahanian clarifies that off-resonance was calculated individually for each artery based on its anatomical location (Jahanian, p. 1205, 'In vivo results', ¶[4]). This confirms that such high off-resonance regions were not only present but occurred at distinct arterial locations relative to others in the labeling plane. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Jahanian to produce a non-uniform magnetic field that includes one or more regions where nuclear spins are at least 100 Hz off-resonance of the RF labeling field at a location of the remainder of the plurality of arteries. The benefit of this combination is improved understanding and management of off-resonance field effects in ASL imaging environments, enabling more robust and reliable labeling strategies across anatomically diverse arterial structures.
Regarding claim 15, the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia does not explicitly teach that the non-uniform magnetic field includes one or more regions where nuclear spins are at least 100 Hz off-resonance of the RF labeling field at a location of the remainder of the plurality of arteries. Rather, the combined art discloses the use of direct currents during the RF excitation pulse to shape a magnetic field in the labeling region (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil', ¶5). It does not specify that the resulting magnetic field includes one or more regions that shift the nuclear spins by at least 100 Hz off-resonance from the RF labeling field or where these shifts occur in relation to other arteries. Jahanian reports measured off-resonance values across multiple arteries in human subjects, including the left vertebral (LV), right vertebral (RV), left carotid (LC), and right carotid (RC) arteries. Table 2 shows that several of these arteries experience frequency shifts greater than ±100 Hz at the tagging plane (Jahanian, p. 1207, Table 2, 'In vivo results'). Moreover, Jahanian clarifies that off-resonance was calculated individually for each artery based on its anatomical location (Jahanian, p. 1205, 'In vivo results', ¶[4]). This confirms that such high off-resonance regions were not only present but occurred at distinct arterial locations relative to others in the labeling plane. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, Helle, and Hernandez-Garcia in view of Jahanian to produce a non-uniform magnetic field that includes one or more regions where nuclear spins are at least 100 Hz off-resonance of the RF labeling field at a location of the remainder of the plurality of arteries. The benefit of this combination is improved understanding and management of off-resonance field effects in ASL imaging environments, enabling more robust and reliable labeling strategies across anatomically diverse arterial structures.
Claims 19 is rejected under 35 U.S.C. 103 as being unpatentable over Stockmann et al. (Stockmann, Jason P, and Lawrence L Wald. “In Vivo B0 Field Shimming Methods for MRI at 7 T.” NeuroImage (Orlando, Fla.) 168 (2018): 71–87. Web.), hereto referred as Stockmann, and further in view of Zhao et al. (Zhao, Li et al. “Improving the Robustness of Pseudo‐continuous Arterial Spin Labeling to Off‐resonance and Pulsatile Flow Velocity.” Magnetic resonance in medicine 78.4 (2017): 1342–1351. Web.), hereto referred as Zhao, and further in view of Juchem et al. (Juchem, Christoph et al. “Multi-Coil Shimming of the Mouse Brain.” Magnetic resonance in medicine 66.3 (2011): 893–900), hereto referred as Juchem, and further in view of Hernandez-Garcia et al. (Hernandez-Garcia, Luis, Anish Lahiri, and Jonas Schollenberger. “Recent Progress in ASL.” NeuroImage (Orlando, Fla.) 187 (2019): 3–16. Web.), hereto referred as Hernandez-Garcia.
Regarding claim 19, Stockmann teaches a method for perfusion magnetic resonant imaging (MRI) within an MRI system having at least one RF coil configured to transmit an RF signal (Stockmann, p. 10, Abstract: "We discuss and compare several promising hardware approaches for static and dynamic B0 shimming using either higher-order spherical harmonic shim coils or multi-coil shim arrays..."; p. 13, 'Integrating B0 shim field generation into the RF receive coil', 15: "In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse...", showing that the method is implemented within an MRI system using advanced coil arrays and RF excitation pulses are transmitted by the system).
Stockmann does not explicitly teach that the method comprises providing a coil array configured for placement on a patient in the MRI system at a labeling plane that bisects a plurality of arteries. Rather, Stockmann describes a close-fitting coil array shaped to conform to the head of a subject during MRI, with the array used for both RF and shim functions (Stockmann, p. 12, 'Integrating B0 shim field generation into the RF receive coil': "A departure of the integrated ΔB0/Rx approach was to utilize the same close-fitting helmets used in RF arrays..."). It does depict bisection of arteries (Stockmann Figs. 1-2), which illustrate the positioning of the coil array relative to vascular anatomy, but does not explain or highlight that feature as part of the labeling configuration or imaging strategy. Zhao, who looks at spin labeling, identifies multiple positions used for pseudo-continuous arterial spin labeling, including one (L2) located above the carotid artery bifurcation and below the V3 segment, selected to encompass both the carotid and vertebral arteries (Zhao, p. 7, 'Volunteer Experiments and Evaluations': "Three locations were chosen based on the angiogram and inferior brain anatomy. As illustrated in Figure 3: L1: on the inferior border of the cerebellum (6); L2: above the carotid artery bifurcation and below the V3 segment..."). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the multi-coil shim array of Stockmann for use during the ASL labeling operation of Zhao such that the generated shim field modifies B0 conditions at the labeling plane selected in Zhao, because Zhao teaches the anatomical location of the labeling plane intersecting major feeding arteries and Stockmann teaches generating spatially controlled B0 fields in patient anatomy using a conformal multi-coil array (Zhao, p. 6, 'Volunteer Experiments and Evaluations': “All imaging was performed… using the body coil for transmission and an eight-channel head array for reception. PCASL was performed with repeated Hann RF pulses….”). Configuring Stockmann’s multi-coil shim array for use during Zhao’s ASL labeling operation would result in generation of a controlled B0 field at the labeling plane selected in Zhao, because Stockmann teaches spatially shaping B0 within a region of interest using a conformal coil array and Zhao teaches selection of a labeling plane intersecting the targeted arteries. The predictable result would be the ability to shape the magnetic field at the labeling plane location taught by Zhao. The benefit of the combination is a compact, anatomically conforming array (Stockmann) that enables effective arterial spin labeling across multiple targeted arteries (Zhao).
The combined Stockmann and Zhao does not fully teach capturing one or more first MRI images of the patient anatomy at a first imaging plane that is different from the labeling plane. Rather, the combined art shows acquisition of EPI and anatomical reference images across multiple imaging slices (Stockmann, p. 28, Fig. 5), supporting image quality assessment and shimming performance. It does not explicitly describe the relationship between those slices and any RF labeling plane. Zhao independently defines a labeling plane using anatomical landmarks (Zhao, p. 7, 'Volunteer Experiments'; Fig. 3), which is spatially distinct from the imaging slices used for capturing perfusion effects. The separate identification of the labeling plane and imaging plane is a core aspect of pseudo-continuous arterial spin labeling (PCASL). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have interpreted the combined Stockmann and Zhao's imaging slices as being distinct from Zhao's labeling plane, as this reflects standard ASL imaging configurations. The benefit of this combination is enhanced accuracy in perfusion quantification by enabling imaging at a site spatially separated from the RF tagging region, reducing interference and improving contrast reliability.
The combined Stockmann and Zhao does not fully teach applying a series of RF pulses to the at least one RF coil, to create an RF labeling field in the labeling plane. Rather, the combined art describes that RF pulses are transmitted by an RF coil of the MRI system while the shim array currents are applied concurrently. In particular, it notes that excitation pulses are coordinated with current application, beginning 500 µs before the RF event (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil': "In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse ..."). It does not describe the use of repeated RF pulses for arterial spin labeling. Zhao specifies that pseudo-continuous ASL was implemented using repeated Hann RF pulses, with each pulse lasting 500 us and separated by a 700 µs gap (Zhao, p. 6, 'Volunteer Experiments and Evaluations': "PCASL was performed with repeated Hann RF pulses.... RF duration was 500us and the gap between RFs was 700us."). Zhao illustrates a standard and clinically accepted PCASL configuration, including the timing, labeling geometry, and pulse pattern required for accurate perfusion labeling. This clearly discloses the type of repeated RF labeling structure required for generating the labeling field. Although Stockmann describes RF pulses and shim fields in the context of image acquisition, the structure and timing are compatible with ASL labeling sequences when combined with Zhao's pulse parameters. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann and Zhao to apply Zhao’s PCASL pulse train at the labeling plane while concurrently operating Stockmann’s independently driven multi-coil shim array, because Zhao teaches the RF labeling sequence and Stockmann teaches timed DC shim control relative to RF excitation events. The benefit of the combination is concurrent application of PCASL labeling RF pulses and tailored B0 conditions at the labeling plane for improved labeling robustness.
The combined Stockmann and Zhao does not fully or explicitly teach that the method comprises applying a first set of direct currents to a plurality of coils in the coil array while the series of RF pulses are applied, each coil of the plurality of coils in the coil array being supplied with a different direct current such that a first resulting field in the labeling plane results in a labeling region where a nuclear spin of blood is more on-resonance with the RF labeling field than without the first set of direct currents.
Rather, the combined art teaches a multi-coil (MC) shim array having independently driven channels with per-channel current control (Stockmann, p. 13, “In single-channel tests the output was ramped from 0 to 2 A starting 500 µs before the beginning of the RF excitation pulse…”). Stockmann further teaches that “By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum” (Stockmann, p. 6), and that “Efforts toward further improvement by dynamically switching the SH shims on a slice-by-slice basis have also been pursued” (Stockmann, p. 8). Stockmann also demonstrates slice-optimized multi-coil shimming during RF operation (Stockmann, p. 34, Fig. 10; p. 35, Fig. 10). Thus, Stockmann shows per-channel hardware and timed coordination of direct current application relative to RF excitation events. However, Stockmann does not expressly describe applying such independently controlled per-coil direct currents during a pseudo-continuous arterial spin labeling (PCASL) RF pulse train at a labeling plane, and does not expressly describe doing so to shift a labeling region toward on-resonance with a PCASL RF labeling field.
Juchem explicitly teaches, during multi-coil shimming, loading “a single set of 48 individual current values” and that “[t]he corresponding currents were generated by 48 individual amplifiers”, which evidences supplying different DC current values across a plurality of coils/channels (Juchem, p. 4, “Global and Slice-Specific Shimming of the Mouse Brain”).
Zhao teaches applying a series of RF pulses at a defined labeling plane for pseudo-continuous arterial spin labeling (Zhao, p. 6–7). Zhao further teaches that off-resonance conditions affect PCASL labeling such that frequency offsets reduce labeling performance (Zhao, p. 4, “Off-Resonance Effects on PCASL”, 13), and explains on-resonance labeling efficiency behavior (Zhao, p. 5, “On Resonance Efficiency and Flow Velocity”; Fig. 1). These teachings establish that bringing spins closer to on-resonance with the RF labeling field increases labeling efficiency relative to off-resonant conditions.
Accordingly, when Zhao’s labeling RF pulse train is applied at the labeling plane, and Stockmann’s independently driven per-coil direct currents are applied during RF operation using coil-specific current values as taught by Juchem, the resulting field in the labeling plane is spatially shaped by the per-coil direct currents (Stockmann, p. 6; p. 8; p. 34, Fig. 10). Because multi-coil DC shimming alters the local B0 magnetic field within a selected region of interest (Stockmann, p. 6; p. 8), the corresponding local resonance frequency offset at the labeling plane is modified relative to the unshimmed condition. In view of Zhao’s teaching that off-resonance conditions reduce PCASL labeling performance (Zhao, p. 4) and that on-resonance behavior governs labeling efficiency (Zhao, p. 5; Fig. 1), shaping the B0 field at the labeling plane using different per-coil direct currents produces a labeling region in which blood spins are more on-resonance with the applied RF labeling field than without the applied direct currents.
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Stockmann and Zhao in view of Juchem to apply independently controlled, per-coil direct currents during Zhao’s PCASL labeling RF pulse sequence at the labeling plane, because Stockmann teaches per-channel shim current drive capability with timing coordination relative to RF excitation events (Stockmann, p. 13), Zhao teaches applying the PCASL RF labeling pulse train at a defined labeling plane and teaches that off-resonance reduces labeling effectiveness (Zhao, p. 6–7; p. 4), and Juchem expressly teaches implementing multi-coil shimming using coil-specific current settings across a plurality of coils/channels (Juchem, p. 4). Combining these teachings would have involved applying the known per-channel current-setting methodology of Juchem to the multi-coil hardware platform of Stockmann while operating the known PCASL labeling sequence of Zhao, which represents the predictable use of prior art elements according to their established functions. The predictable result would be generation of a spatially tailored labeling field environment at the labeling plane through different direct current values supplied to different coils of the array, producing a labeling region in which blood spins are more on-resonance with the RF labeling field than without the applied direct currents, thereby improving labeling efficiency in view of Zhao’s off-resonance and on-resonance efficiency teachings (Zhao, p. 4; p. 5; Fig. 1). The benefit of the combination is improved labeling efficiency and robustness by reducing off-resonance effects in the labeling region during PCASL, thereby enhancing perfusion signal quality using established multi-coil shimming control.
The combined Stockmann, Zhao, and Juchem does not fully teach capturing one or more second MRI images of the patient anatomy at the first imaging plane after a perfusion delay while applying a second set of direct currents to the plurality of coils in the coil array, the second set of direct currents being different than the first set of direct currents. As shown in the combined art (Stockmann FIG. 9-10), dynamic shimming is performed during EPI acquisition corresponding to the imaging step, which reinforces that the shimming operation occurs concurrently with image capture, satisfying the temporal relationship of the imaging phase in the claim. The combined art also shows a pulse sequence that captures co-registered EPI slices at an imaging plane and further teaches dynamic shimming capability during acquisition (e.g., Stockmann, p. 6, Problems caused by static B0 inhomogeneity: "By using the available degrees of freedom to shim a much smaller ROI, dynamic shimming can achieve superior B0 homogeneity compared to a global optimum", and p. 8, Dynamic spherical harmonic shimming: "Efforts toward further improvement by dynamically switching the SH shims on a slice-by-slice basis have also been pursued"), which provides the express means to apply a second (different) DC shim pattern during the imaging phase as compared to any DC pattern used during labeling. However, the combined art does not teach that the second set of direct currents is applied concurrently with acquisition of the second images at the first imaging plane after a perfusion delay in an ASL/PCASL context, nor that the second set is expressly defined as different from the first labeling-phase set, nor that these two sets are coordinated across distinct labeling and imaging planes linked by a PLD.
Zhao discloses a standard ASL/PCASL workflow in which (1) labeling is performed at a dedicated labeling plane using repeated RF pulses, (ii) labeling is followed by a post-labeling delay (PLD) (e.g.. 1.8 s) to allow tagged blood to traverse to the imaging slab, and (iii) images are then acquired at a first imaging plane that is different from the labeling plane (Zhao, p. 6-7, Volunteer Experiments and Evaluations; FIG. 3). Zhao further explains that labeling parameters were optimized for robustness and on-resonance inversion efficiency in the presence of off-resonance and pulsatile flow (e.g., B1, gradient waveform/ratio), and reports paired acquisitions comparing standard versus optimized (Optimal B1 and Gradient) labeling settings at the same location. Because Zhao performs labeling at a dedicated labeling plane, then waits a PLD (e.g., 1.8 s) and acquires images at a distinct imaging plane, the B0 objective at readout (distortion control in the imaging slab) is different from the B0 objective at labeling (on-resonance inversion at the labeling plane), motivating a different DC shim set during the second images. These teachings fill the gaps as follows: Zhao supplies the PLD requirement and the explicit separation of labeling and imaging planes, and establishes that labeling has different B0 demands (on-resonance at the labeling plane) than imaging (distortion control in the imaging slab). Consequently, when combined with Stockmann's dynamic slice-wise shimming at readout, Zhao's workflow and optimization guidance motivate using a second, different DC set during the second images than any DC set used during labeling, meeting the amended limitation. Moreover, Zhao's optimization of labeling parameters demonstrates the broader principle of parameter optimization across different sequence phases (labeling and imaging) providing direct motivation to separately tune DC shims for each phase, consistent with Stockmann's slice-by-slice optimization of B0 homogeneity during EPI acquisition. This combined approach would have been recognized by one of ordinary skill in the art as beneficial for maintaining field uniformity through temporal transitions from labeling to imaging to ensure accurate perfusion quantification.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined Stockmann, Zhao, and Juchem, in view of Zhao by (i) performing PCASL labeling at the labeling plane with a first DC current set appropriate for labeling and then (ii) after the PLD, acquiring the second images at the imaging plane while concurrently applying a different, slice-optimized DC shim set during readout to reduce B0 inhomogeneity, thereby meeting the amended limitation. Under KSR, the tasks present a finite set of predictable choices (reuse the labeling DC pattern at readout vs. compute a slice-optimized imaging DC pattern); Stockmann teaches dynamic changes during acquisition and shows predictable improvement in slice homogeneity, yielding a reasonable expectation of success. Zhao (labeling) and Stockmann (imaging) each explicitly teach optimization for their respective tasks; adopting different DC sets for those distinct tasks would have been routine and expected. The benefit of the combination is twofold. Zhao provides improved labeling robustness by teaching optimized pseudo-continuous arterial spin labeling (PCASL) parameters that enhance on-resonance inversion efficiency and vessel selectivity at the labeling plane. Stockmann provides improved image quality by using dynamic, slice-specific B0 correction during acquisition of the second images, which reduces distortion and enhances signal-to-noise ratio. Together, the combined teachings yield predictable and complementary improvements in inversion efficiency, perfusion accuracy, and image fidelity across the respective labeling and imaging phases.
The combined Stockmann, Zhao, and Juchem does not fully teach comparing the one or more first MRI images and the one or more second MRI images to generate a map of perfusion. Rather, the combined art demonstrates the use of EPI and anatomical images across imaging slices for evaluating the spatial uniformity of B0 shim performance (Stockmann, p. 34, Fig. 9). While this confirms image comparison is part of the system's diagnostic workflow, it does not describe using label/control pairs or computing perfusion. Hernandez-Garcia, who investigates Arterial Spin Labeling, explicitly teaches the use of subtraction between control and labeled images to quantify the amount of blood entering tissue during an ASL labeling period, providing a direct method for generating perfusion maps (Hernandez-Garcia, p. 3, 'Introduction', FIG. 1). This process implicitly reflects perfusion through arterial pathways, such that the resulting maps represent blood flow associated with at least one artery contributing to the labeled region. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann and Zhao in view of Hernandez-Garcia to apply image subtraction techniques to labeled and control ASL images to generate perfusion maps. The benefit of this combination is the integration of physiologic blood flow mapping with Stockmann's high-fidelity anatomical imaging and shim-optimized field performance.
Claims 20 is rejected under 35 U.S.C. 103 as being unpatentable over Stockmann et al. (Stockmann, Jason P, and Lawrence L Wald. “In Vivo B0 Field Shimming Methods for MRI at 7 T.” NeuroImage (Orlando, Fla.) 168 (2018): 71–87. Web.), hereto referred as Stockmann, and further in view of Zhao et al. (Zhao, Li et al. “Improving the Robustness of Pseudo‐continuous Arterial Spin Labeling to Off‐resonance and Pulsatile Flow Velocity.” Magnetic resonance in medicine 78.4 (2017): 1342–1351. Web.), hereto referred as Zhao, and further in view of Juchem et al. (Juchem, Christoph et al. “Multi-Coil Shimming of the Mouse Brain.” Magnetic resonance in medicine 66.3 (2011): 893–900), hereto referred as Juchem, and further in view of Hernandez-Garcia et al. (Hernandez-Garcia, Luis, Anish Lahiri, and Jonas Schollenberger. “Recent Progress in ASL.” NeuroImage (Orlando, Fla.) 187 (2019): 3–16. Web.), hereto referred as Hernandez-Garcia, and further in view of Jahanian et al. (Jahanian H, Noll DC, Hernandez-Garcia L. B0 field inhomogeneity considerations in pseudo-continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy. NMR Biomed. 2011 Dec;24(10):1202-9), hereto referred as Jahanian.
The combined Stockmann, Zhao, Juchem, and Hernandez-Garcia teaches claim 19 as described above.
Regarding claim 20, the combined Stockmann, Zhao, Juchem, and Hernandez-Garcia do not explicitly teach that the first resulting field in the labeling plane includes one or more regions where nuclear spins are at least 100 Hz off-resonance of the RF labeling field. Rather, the combined art describes field shaping via direct current application during RF excitation (Stockmann, p. 13, 'Integrating B0 shim field generation into the RF receive coil', ¶5), and provides the resonance efficiency context for ASL labeling (Zhao, p. 5, ‘On Resonance Efficiency and Flow Velocity’, ¶5; Zhao, p. 4, 'Off-Resonance Effects on PCASL', ¶3). Together, they show how local magnetic fields in the labeling plane may be adjusted to enhance resonance alignment. However, it does not teach that specific regions become off-resonance by at least 100 Hz. Jahanian, who measured off-resonance values for multiple arteries in vivo, reports that several regions within the tagging plane exhibit nuclear spin resonance frequencies that differ from the labeling frequency by over 100 Hz (Jahanian, Table 2, p. 1207, 'In vivo results'). It also details the anatomical basis for these differences (Jahanian, p. 1205, 'In vivo results', ¶[4]), confirming that distinct arterial regions experience large shifts in resonance. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Stockmann, Zhao, Juchem, and Hernandez-Garcia in view of Jahanian to produce a labeling plane where nuclear spins in at least one region are off-resonance from the RF labeling field by at least 100 Hz. Jahanian confirms the physiological likelihood of this outcome, and Stockmann provides the programmable control needed to realize it through targeted current configuration. The benefit is precise spatial modulation of spin resonance within the labeling plane, enabling vessel-specific tagging or suppression based on frequency alignment.
Response to Arguments
35 U.S.C. §103
Applicant's arguments filed 2/17/2026, page 8-10, regarding the previous 103 Rejections of claims 1-4, 7-8, 10-13, 16-17, and 19-20 have been fully considered but 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 (that is, there are new grounds of rejection).
Applicant's arguments filed 2/17/2026, page 8-10,, regarding the previous 103 Rejection of claim 1, 10, 19, and 21 has been fully considered but are not persuasive as shown below.
Applicant’s Argument: Applicants argue that Stockmann does not describe applying a different direct current to each coil of a plurality of coils, and that Zhao, Helle, and Hernandez-Garcia do not remedy this asserted deficiency.
Examiner’s Response: The argument is not persuasive because the rejection has been clarified to rely on Juchem for the expressly recited limitation of each coil of the plurality of coils in the coil array being supplied with a different direct current. Juchem expressly teaches, during multi-coil shimming, loading "a single set of 48 individual current values" and that "[t]he corresponding currents were generated by 48 individual amplifiers," which evidences coil-specific or channel-specific direct current values across a plurality of coils or channels. As set forth in the amended rejection, these Juchem teachings are applied to the multi-coil shim hardware platform and time coordination of Stockmann, in combination with Zhao’s PCASL labeling pulse train at a defined labeling plane, to meet the amended limitation.
Applicant’s Argument: Applicants further argue that because amended claim 1 is not shown to be obvious, then claims dependent therefrom similarly are not shown to be obvious.
Examiner’s Response: The argument is not persuasive because it is premised on the alleged deficiency that Stockmann, Zhao, Helle, and Hernandez-Garcia do not teach per-coil different direct currents. As discussed above, the amended rejection relies on Juchem for coil-specific current settings and thus addresses the asserted deficiency. Therefore, the dependency-based argument does not establish error in the amended rejection.
Applicant’s Argument: Applicants assert that claim 10 and claim 19 were amended similarly to claim 1 and, for the same reasons asserted for claim 1, are not shown to be obvious, and that their dependent claims accordingly are not shown to be obvious.
Examiner’s Response: The argument is not persuasive for the same reasons set forth above. The amended rejections of claims 10 and 19 rely on Juchem for the coil-specific current values limitation and therefore are not defeated by the asserted deficiency directed to Stockmann alone.
Applicant’s Argument: Applicants present new claim 21, but do not provide a separate, claim-specific argument directed to the added limitation of pausing the first set of direct currents while a main body coil of the MRI system applies background field suppression pulses.
Examiner’s Response: To the extent Applicants rely on the foregoing arguments for claim 1 to support allowability of new claim 21, those arguments are not persuasive for the reasons set forth above. Further, claim 21 is rejected under 35 U.S.C. § 103 on the basis that, in view of the combined teachings applied to claim 1 (including applying a first set of direct currents during Zhao’s labeling RF pulse sequence), it would have been obvious to pause the shim-array direct currents during background field suppression pulses as a routine sequencing and interference-avoidance measure during interleaved ASL acquisitions, as background suppression pulses are known to be interleaved with labeling and can create transient fields or interactions that would undesirably interfere with the shim field during labeling. Thus, the amended rejection maintains that claim 21 is unpatentable over the applied combination.
Applicant’s Argument: Applicant requests a rejoinder upon Allowance.
Examiner’s Response: The request is not persuasive. The rejections set forth in the Office Action are maintained as to the currently pending claims. The amendments and arguments have been fully considered. The Office does not find that the present application is in condition for allowance and therefore a rejoinder is not appropriate.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/AARON MERRIAM/Examiner, Art Unit 3791
/MATTHEW KREMER/Primary Examiner, Art Unit 3791