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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 .
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The information disclosure statements (IDS) were submitted on 5/30/2024, 7/18/2025, and 7/18/2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (U.S. Pub. No. 20200390361) hereinafter Wang, in view of Helle et al. (U.S. Pat. No. 10871538) hereinafter Helle.
Regarding claim 1, primary reference Wang teaches:
A system for magnetic resonance imaging of water exchange processes (abstract), comprising:
acquire, from the imaging volume, at a plurality of time points, a plurality of water magnetic resonance signals, said plurality of water magnetic resonance signals comprising a first subset of signals that are labeled for a water exchange process and a second subset of signals that are not labeled ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides a labeled water in brain compartments and unlabeled control signals as a second subset of signals; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072]-[0075], labeled signals); and
a data processor configured to:
generate, from the first subset of signals, a plurality of labeled images ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides a labeled water in brain compartments and unlabeled control signals as a second subset of signals; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072]-[0075], labeled signals);
generate, from the second subset of signals, a plurality of control images corresponding to the plurality of labeled images ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides unlabeled control signals as a second subset of signals in which a control image is generated; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072]-[0075], labeled signals); and
calculate one or more parameters to characterize a water exchange process in the imaging volume between a first water compartment and a second water compartment based on the labeled images and the corresponding control images ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides unlabeled control signals as a second subset of signals in which a control image is generated; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072], “Kinetic models were proposed to map the whole-brain transcapillary water exchange based on the T2 and T2* differences in the 2 compartments”; [0073]-[0075], labeled signals and “k.sub.w as a sensitive marker of BBB water exchange).
Primary reference Wang fails to teach:
a primary magnet configured to provide a magnetic field over an imaging volume;
a magnetic gradient coil configured to generate a spatial encoding in the magnetic field;
a radiofrequency (RF) coil configured to:
However, the analogous art of Helle a magnetic resonance imaging for an arterial spin labeling scan method (abstract) teaches:
a primary magnet configured to provide a magnetic field over an imaging volume (col 6, lines 27-67, main magnet);
a magnetic gradient coil configured to generate a spatial encoding in the magnetic field (col 6, lines 27-67, local array coils form gradient coils);
a radiofrequency (RF) coil (col 6, lines 27-67, body RF coil) configured to:
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang to incorporate the magnetic resonance imaging system components as taught by Helle because it provides for a capable magnetic resonance scanner for generating a temporally constant magnetic field, apply RF pulses to saturate and excite resonance, and selected particular regions for imaging (Helle, col 6, lines 27-67). This leads to precise magnetic resonance imaging.
Regarding claim 14, the combined references of Wang and Helle teach all of the limitations of claim 1. Primary reference Wang further teaches:
wherein the parameters to characterize the water exchange process comprise at least one of a water exchange transit time expressed in units of time, and a flow rate expressed in units of volume per mass per unit time ([0008], arterial transit time and water exchange rate; [0027], exchange rate of water; [0028]; [0039], arterial transit time and water exchange rate; [0047], arterial transit time and water exchange rate; claims 10-11; [0066]).
Regarding claim 15, the combined references of Wang and Helle teach all of the limitations of claim 1. Primary reference Wang further teaches:
wherein the parameters to characterize the water exchange process are calculated using a difference of the labeled images and the corresponding control images ([0063], “Control/label images were corrected for rigid head motion offline using SPM12 (Wellcome Trust Centre for Neuroimaging, UCL, London, UK) and subtracted to obtain perfusion images.”).
Regarding claim 16, primary reference Wang teaches:
A method for magnetic resonance imaging of water exchange processes (abstract), comprising:
receiving a plurality of water magnetic resonance signals from an imaging volume at a plurality of time points, said plurality of water magnetic resonance signals comprising a first subset of signals that were labeled for a water exchange process and a second subset of signals that were not labeled ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides a labeled water in brain compartments and unlabeled control signals as a second subset of signals; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072]-[0075], labeled signals);
generating, from the first subset of signals, a plurality of labeled images ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides a labeled water in brain compartments and unlabeled control signals as a second subset of signals; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072]-[0075], labeled signals);
generating, from the second subset of signals, a plurality of control images corresponding to the plurality of labeled images ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides unlabeled control signals as a second subset of signals in which a control image is generated; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072]-[0075], labeled signals); and
calculating one or more parameters to characterize a water exchange process in the imaging volume between a first water compartment and a second water compartment based on the labeled images and the corresponding control images ([0006]-[0008], water exchange across the blood brain barrier is measured using arterial spin labeling imaging scanning, which provides unlabeled control signals as a second subset of signals in which a control image is generated; [0023], water labeling; [0024]-[0027]; [0028], control images form the unlabeled signals; [0029]-[0031]; [0039]-[0040], labeling of signals of water within brain tissue compartments; [0045]-[0047], labeled water signals across time; [0049]-[0050]; [0058], label/control; [0061], label corresponds to the labeled water and control corresponds to unlabeled signals; [0063], control and labeled images; [0072], “Kinetic models were proposed to map the whole-brain transcapillary water exchange based on the T2 and T2* differences in the 2 compartments”; [0073]-[0075], labeled signals and “k.sub.w as a sensitive marker of BBB water exchange).
Primary reference Wang fails to teach:
receiving a plurality of water magnetic resonance signals that were acquired by a radiofrequency (RF) coil from an imaging volume
However, the analogous art of Helle a magnetic resonance imaging for an arterial spin labeling scan method (abstract) teaches:
acquired by a radiofrequency (RF) coil from an imaging volume (col 6, lines 27-67, body RF coil)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang to incorporate the magnetic resonance imaging system components as taught by Helle because it provides for a capable magnetic resonance scanner for generating a temporally constant magnetic field, apply RF pulses to saturate and excite resonance, and selected particular regions for imaging (Helle, col 6, lines 27-67). This leads to precise magnetic resonance imaging.
Claims 2-3, 8-9, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, in view of Helle as applied to claims 1 or 16 above, and further in view of Nishihara et al. (U.S. Pub. No. 20120212223) hereinafter Nishihara.
Regarding claim 2, the combined references of Wang and Helle teach all of the limitations of claim 1. Primary reference Wang further fails to teach:
wherein the RF coil is further configured to null water signals from the second water compartment at a particular time
However, the analogous art of Nishihara of a magnetic resonance imaging apparatus for two-dimensional excitation of a region (abstract) teaches:
wherein the RF coil is further configured to null water signals from the region of interest at a particular time ([0089]-[0090], null time in which the echo signal is acquired for water becoming essentially zero from the second inversion pulse).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang and Helle to incorporate the null water signals as taught by Nishihara because an image of only the arterial blood is obtained by acquiring an echo signal after Null Time which is a period until an echo signal of water becomes substantially zero from the second inversion pulse (Nishihara, [0089]).
Regarding claim 3, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the RF coil is configured to null water signals from the second water compartment by applying an inversion pulse at an interval prior to the particular time, said interval being determined based on a T1 relaxation time constant associated with the second water compartment
However, the analogous art of Nishihara of a magnetic resonance imaging apparatus for two-dimensional excitation of a region (abstract) teaches:
wherein the RF coil is configured to null water signals from the water region by applying an inversion pulse at an interval prior to the particular time, said interval being determined based on a T1 relaxation time constant associated with the water region ([0089]-[0090], “Since T1, which is a time constant of the longitudinal relaxation, of fat is smaller than T1 of water, relaxation of the longitudinal magnetization of fat is earlier than relaxation of the longitudinal magnetization of water. For this reason, the size of the longitudinal magnetization becomes zero by the longitudinal relaxation. As a result, the Null Time at which a detected echo signal becomes substantially zero in fat becomes earlier than that in water.”; [0091]; combined with Wang in the combined invention teaches to the second water compartment as applied to the overall pulse sequence).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the T1 relaxation time-based inversion pulse echo signal as taught by Nishihara because at the Null Time of water, the longitudinal magnetization of fat is greatly recovered to detect echo signals from fat (Nishihara, [0090]). This leads to higher quality output images.
Regarding claim 8, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the plurality of time points are subsequent to the particular time
However, the analogous art of Nishihara of a magnetic resonance imaging apparatus for two-dimensional excitation of a region (abstract) teaches:
wherein the plurality of time points are subsequent to the particular time ([0089],. Echo signals are acquired after the null time which forms the plurality of time points for acquiring a signal; [0090]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the acquiring of time points after the null time as taught by Nishihara because an echo signal of water becomes substantially zero from the second inversion pulse (Nishihara, [0089]). This leads to improved contrast within the image and better quality output images.
Regarding claim 9, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 8. Primary reference Wang further fails to teach:
wherein the water magnetic resonance signals are acquired at the plurality of time points using a pulse sequence that suppresses water signals from the first water compartment to provide improved contrast for water signals from the second water compartment
However, the analogous art of Nishihara of a magnetic resonance imaging apparatus for two-dimensional excitation of a region (abstract) teaches:
wherein the water magnetic resonance signals are acquired at the plurality of time points using a pulse sequence that suppresses water signals from the first water compartment to provide improved contrast for water signals from the second water compartment ([0089],. Echo signals are acquired after the null time which forms the plurality of time points for acquiring a signal; [0090]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the acquiring of time points after the null time as taught by Nishihara because an echo signal of water becomes substantially zero from the second inversion pulse (Nishihara, [0089]). This leads to improved contrast within the image and better quality output images.
Regarding claim 17, the combined references of Wang and Helle teach all of the limitations of claim 16. Primary reference Wang further fails to teach:
wherein water signals from the second water compartment were nulled by the RF coil at a particular time
However, the analogous art of Nishihara of a magnetic resonance imaging apparatus for two-dimensional excitation of a region (abstract) teaches:
wherein water signals from the second water compartment were nulled by the RF coil at a particular time ([0089]-[0090], null time in which the echo signal is acquired for water becoming essentially zero from the second inversion pulse).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang and Helle to incorporate the null water signals as taught by Nishihara because an image of only the arterial blood is obtained by acquiring an echo signal after Null Time which is a period until an echo signal of water becomes substantially zero from the second inversion pulse (Nishihara, [0089]).
Regarding claim 18, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 17. Primary reference Wang further fails to teach:
wherein water signals from the second water compartment were nulled by the RF coil by applying an inversion pulse at an interval prior to the particular time, said interval being determined based on a T1 relaxation time constant associated with the second water compartment
However, the analogous art of Nishihara of a magnetic resonance imaging apparatus for two-dimensional excitation of a region (abstract) teaches:
wherein water signals from the water region were nulled by the RF coil by applying an inversion pulse at an interval prior to the particular time, said interval being determined based on a T1 relaxation time constant associated with the water region ([0089]-[0090], “Since T1, which is a time constant of the longitudinal relaxation, of fat is smaller than T1 of water, relaxation of the longitudinal magnetization of fat is earlier than relaxation of the longitudinal magnetization of water. For this reason, the size of the longitudinal magnetization becomes zero by the longitudinal relaxation. As a result, the Null Time at which a detected echo signal becomes substantially zero in fat becomes earlier than that in water.”; [0091]; combined with Wang in the combined invention teaches to the second water compartment as applied to the overall pulse sequence).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the T1 relaxation time-based inversion pulse echo signal as taught by Nishihara because at the Null Time of water, the longitudinal magnetization of fat is greatly recovered to detect echo signals from fat (Nishihara, [0090]). This leads to higher quality output images.
Claims 4 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, in view of Helle, in further view of Nishihara as applied to claims 2 or 17 above, and further in view of Qin (U.S. Pat. No. 10330762) hereinafter Qin.
Regarding claim 4, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the RF coil is configured to null water signals from the second water compartment by applying a diffusion pulse with at least one b-value prior to the particular time, said b-value being determined based on an apparent diffusion coefficient (ADC) of the second water compartment
However, the analogous art of Qin of a system and method for measuring blood volume using a labeling method (abstract) teaches:
wherein the RF coil is configured to null water signals from the water compartment by applying a diffusion pulse with at least one b-value prior to the particular time, said b-value being determined based on an apparent diffusion coefficient (ADC) of the water compartment (col 7, lines 1-50, includes apparent diffusion coefficient of the water compartment and includes the VS pulse trains for diffusion weighting gradient with a b-vlue for the blood water signal in the labeled compartment).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the diffusion pulse with b-time based on ADC as taught by Qin because with different flowing velocities in individual segments of the microvasculature and also limited gradient performance on the clinical scanners, the percentage of blood being suppressed in each microvascular compartment, or the labeling efficiency varies. Using the additional signal processing accounts for the signal characteristics and leads to higher quality output images (Qin, col 7, lines 1-50).
Regarding claim 19, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 17. Primary reference Wang further fails to teach:
wherein water signals from the second water compartment were nulled by the RF coil by applying a diffusion pulse with at least one b-value prior to the particular time, said b-value being determined based on an apparent diffusion coefficient (ADC) of the second water compartment
However, the analogous art of Qin of a system and method for measuring blood volume using a labeling method (abstract) teaches:
wherein water signals from the water compartment were nulled by the RF coil by applying a diffusion pulse with at least one b-value prior to the particular time, said b-value being determined based on an apparent diffusion coefficient (ADC) of the water compartment (col 7, lines 1-50, includes apparent diffusion coefficient of the water compartment and includes the VS pulse trains for diffusion weighting gradient with a b-vlue for the blood water signal in the labeled compartment).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the diffusion pulse with b-time based on ADC as taught by Qin because with different flowing velocities in individual segments of the microvasculature and also limited gradient performance on the clinical scanners, the percentage of blood being suppressed in each microvascular compartment, or the labeling efficiency varies. Using the additional signal processing accounts for the signal characteristics and leads to higher quality output images (Qin, col 7, lines 1-50).
Claims 5 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, in view of Helle, in further view of Nishihara as applied to claims 2 or 17 above, and further in view of Lowery et al. (CA2710191A1) hereinafter Lowery (see attached FOR reference for citations).
Regarding claim 5, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the RF coil is configured to null water signals from the second water compartment by applying a Carr-Purcell-Meiboom-Gill (CPMG) pulse with an echo time ending at the particular time, said echo time being determined based on a T2 relaxation time constant associated with the second water compartment
However, the analogous art of Lowery of a nuclear magnetic resonance sample analysis system (abstract) teaches:
wherein the RF coil is configured to null water signals from the water compartment by applying a Carr-Purcell-Meiboom-Gill (CPMG) pulse with an echo time ending at the particular time, said echo time being determined based on a T2 relaxation time constant associated with the water compartment ([079], CPMG sequence based on a T2 relaxation time constant for the sample; [081]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the CPMG pulse based on T2 as taught by Lowery because optimization of pulse lengths and pulse parameters for a CPMG sequence enables magnetization at a null time during the readout and precise detection of a first or second sample as desired (Lowery, [081]). This leads to less signal noise and higher output quality.
Regarding claim 20, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 17. Primary reference Wang further fails to teach:
wherein water signals from the second water compartment were nulled by the RF coil by applying a Carr-Purcell-Meiboom-Gill (CPMG) pulse with an echo time ending at the particular time, said echo time being determined based on a T2 relaxation time constant associated with the second water compartment
However, the analogous art of Lowery of a nuclear magnetic resonance sample analysis system (abstract) teaches:
wherein water signals from the water compartment were nulled by the RF coil by applying a Carr-Purcell-Meiboom-Gill (CPMG) pulse with an echo time ending at the particular time, said echo time being determined based on a T2 relaxation time constant associated with the water compartment ([079], CPMG sequence based on a T2 relaxation time constant for the sample; [081]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the CPMG pulse based on T2 as taught by Lowery because optimization of pulse lengths and pulse parameters for a CPMG sequence enables magnetization at a null time during the readout and precise detection of a first or second sample as desired (Lowery, [081]). This leads to less signal noise and higher output quality.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, in view of Helle, in further view of Nishihara as applied to claim 2 above, and further in view of Guenther (U.S. Pub. No. 20210124000) hereinafter Guenther.
Regarding claim 6, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the RF coil is further configured to acquire the first subset of signals by applying, at the particular time, a first 90-degree pulse and a second 90- degree pulse, wherein the second 90-degree pulse has an opposite phase from the first 90-degree pulse
However, the analogous art of Guenther of a magnetic resonance imaging system for spin labeling of fluid signals (abstract) teaches:
wherein the RF coil is further configured to acquire the first subset of signals by applying, at the particular time, a first 90-degree pulse and a second 90- degree pulse, wherein the second 90-degree pulse has an opposite phase from the first 90-degree pulse ([0091], the 90 degree phase pulse of the ASL pulse is opposite for every other TR which forms the second pulse in opposite phase as the first pulse).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the opposite phase pulse as taught by Guenther because by canceling the effect of the ASL pulses the residual signal of static spins after subtraction of label and control states can be eliminated (Guenther, [0090]). This leads to improved quality of generated subtraction images, leading to better clinical diagnostics.
Regarding claim 7, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the RF coil is further configured to acquire the second subset of signals by applying, at the particular time, a first 90-degree pulse and a second 90- degree pulse, wherein the second 90-degree pulse has a same phase as the first 90-degree pulse
However, the analogous art of Guenther of a magnetic resonance imaging system for spin labeling of fluid signals (abstract) teaches:
wherein the RF coil is further configured to acquire the second subset of signals by applying, at the particular time, a first 90-degree pulse and a second 90- degree pulse, wherein the second 90-degree pulse has a same phase as the first 90-degree pulse ([0091], the 90 degree phase pulse of the ASLIF pulse is the same for every other TR which forms the second pulse in same phase as the first pulse).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the same phase pulse as taught by Guenther because by canceling the effect of the ASL pulses the residual signal of static spins after subtraction of label and control states can be eliminated (Guenther, [0090]). This leads to improved quality of generated subtraction images, leading to better clinical diagnostics.
Claims 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, in view of Helle, in further view of Nishihara as applied to claim 2 above, and further in view of Nedergaard et al. (U.S. Pub. No. 20160000945) hereinafter Nedergaard.
Regarding claim 10, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the first water compartment is interstitial fluid (ISF) and ependyma, the second water compartment is cerebrospinal fluid (CSF), and the water exchange process is a flow from ISF and ependyma to CSF
However, the analogous art of Nedergaard of a measuring of the exchange between brain compartments of CSF-ISF exchange (abstract) teaches:
wherein the first water compartment is interstitial fluid (ISF) and ependyma, the second water compartment is cerebrospinal fluid (CSF), and the water exchange process is a flow from ISF and ependyma to CSF ([0145], CSF-ISF exchange assessed by MRI imaging; [0193], exchange between CSF and ISF compartments; [0455]; [0308] ependyma; the analysis of the exchange forms a teaching to either of the compartments as first and second compartments are interchangeable in light of the recitation in claim 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the CSF-ISF exchange analysis as taught by Nedergaard because it provides quantitative analysis of measuring glio-vascular pathway function in the mammalian brain (Nedergaard, [0003]). This leads to additional insight into cerebral health.
Regarding claim 11, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the second water compartment is interstitial fluid (ISF), the first water compartment is cerebrospinal fluid (CSF), and the water exchange process is a flow from CSF to ISF
However, the analogous art of Nedergaard of a measuring of the exchange between brain compartments of CSF-ISF exchange (abstract) teaches:
wherein the second water compartment is interstitial fluid (ISF), the first water compartment is cerebrospinal fluid (CSF), and the water exchange process is a flow from CSF to ISF ([0145], CSF-ISF exchange assessed by MRI imaging; [0193], exchange between CSF and ISF compartments; [0455]; [0308] ependyma; the analysis of the exchange forms a teaching to either of the compartments as first and second compartments are interchangeable in light of the recitation in claim 1)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the CSF-ISF exchange analysis as taught by Nedergaard because it provides quantitative analysis of measuring glio-vascular pathway function in the mammalian brain (Nedergaard, [0003]). This leads to additional insight into cerebral health.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, in view of Helle, in further view of Nishihara as applied to claim 2 above, and further in view of Russell et al. (U.S. Pat. No. 10551460) hereinafter Russell.
Regarding claim 12, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the second water compartment is white matter (WM), the first water compartment is gray matter (GM), and the water exchange process is a flow from GM to WM
However, the analogous art of Russell of a magnetic resonance imaging system for obtaining quantitative data of a region of interest (abstract) teaches:
wherein the second water compartment is white matter (WM), the first water compartment is gray matter (GM), and the water exchange process is a flow from GM to WM (col 10, line 57 through col 11, line 6, teaches to Pool A as gray matter and Pool B as white matter with the compartment exchange between the two pools determined; the analysis of the exchange forms a teaching to either of the compartments as first and second compartments are interchangeable in light of the recitation in claim 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the white matter and gray matter compartments with exchange as taught by Russell because hydrogen nuclei attached to water molecules and those attached to lipid chains in fat precess at observably different frequencies and therefore white and gray matter, with different compositions can be analyzed to determine brain state characteristics (Russell, col 6, lines 39-52).
Regarding claim 13, the combined references of Wang, Helle, and Nishihara teach all of the limitations of claim 2. Primary reference Wang further fails to teach:
wherein the second water compartment is gray matter (GM), the first water compartment is white matter (WM), and the water exchange process is a flow from WM to GM
However, the analogous art of Russell of a magnetic resonance imaging system for obtaining quantitative data of a region of interest (abstract) teaches:
wherein the second water compartment is gray matter (GM), the first water compartment is white matter (WM), and the water exchange process is a flow from WM to GM (col 10, line 57 through col 11, line 6, teaches to Pool A as gray matter and Pool B as white matter with the compartment exchange between the two pools determined; the analysis of the exchange forms a teaching to either of the compartments as first and second compartments are interchangeable in light of the recitation in claim 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the water exchange labeling and measurement magnetic resonance imaging system of Wang, Helle, and Nishihara to incorporate the white matter and gray matter compartments with exchange as taught by Russell because hydrogen nuclei attached to water molecules and those attached to lipid chains in fat precess at observably different frequencies and therefore white and gray matter, with different compositions can be analyzed to determine brain state characteristics (Russell, col 6, lines 39-52).
Conclusion
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/SEAN A FRITH/Primary Examiner, Art Unit 3798