# US 10,120,049 B2 · System and method of obtaining spatially-encoded NMR parameters from arbitrarily-shaped compartments and linear algebraic modeling

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- Number: US 10,120,049 B2
- Document ID: US10120049B2
- Status: Granted
- Kind: B2
- Application number: 14/715,367
- Filed: 2015-05-18
- Published: 2016-11-24
- Granted: 2018-11-06
- Earliest claimed: 2015-05-18
- Assignees: The Johns Hopkins University
- Applicants: The Johns Hopkins University
- Inventors: Yi Zhang; Jinyuan Zhou; Paul A. Bottomley
- Web page: https://patentgrep.com/patent/US10120049B2

## CPC

- G01R 33/483: with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
- G01R 33/485: based on chemical shift information {[CSI] or spectroscopic imaging, e.g. to acquire the spatial distributions of metabolites}
- G01R 33/50: based on the determination of relaxation times {, e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences}
- G01R 33/5605: {by transferring coherence or polarization from a spin species to another, e.g. creating magnetization transfer contrast [MTC], polarization transfer using nuclear Overhauser enhancement [NOE]}
- G01R 33/56341: {Diffusion imaging}
- G01R 33/56366: {Perfusion imaging}
- G01R 33/5611: {Parallel magnetic resonance imaging, e.g. sensitivity encoding [SENSE], simultaneous acquisition of spatial harmonics [SMASH], unaliasing by Fourier encoding of the overlaps using the temporal dimension [UNFOLD], k-t-broad-use linear acquisition speed-up technique [k-t-BLAST], k-t-SENSE (structural details of arrays of sub-coils G01R33/3415)}
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

An NMR method and system for acquiring and reconstructing a value of an NMR parameter spatially localized to a compartment of interest including performing a first MM of a portion of a sample with a first MRI pulse sequence using the NMR system and using a set of k-space spatial encoding gradients or coil sensitivity encoding maps to obtain a first magnetic resonance image to identify a compartment of interest; generating a second MRI pulse sequence that encodes the NMR parameter with a subset of the set of k-space spatial encoding gradients or the coil sensitivity encoding maps; applying the second MRI pulse sequence using the NMR system to acquire spatial information relating to the NMR parameter from the compartment of interest; segmenting the first magnetic resonance image into a plurality of compartments that includes the compartment of interest; and reconstructing a value of the NMR parameter in the compartment.

## Claims

### Claim 1

A method of localizing a nuclear magnetic resonance (NMR) parameter to at least one compartment of interest of a sample undergoing an NMR examination, comprising:
placing said sample in an NMR system;
performing a first magnetic resonance imaging (MRI) of at least a portion of said sample with a first MRI pulse sequence using said NMR system and using at least one of a set of k-space spatial encoding gradients or coil sensitivity encoding maps to obtain a first magnetic resonance image to identify at least one compartment of interest;
generating a second MRI pulse sequence that encodes said NMR parameter with a subset of said at least one of said set of k-space spatial encoding gradients or said coil sensitivity encoding maps;
applying said second MRI pulse sequence using said NMR system to acquire spatial information relating to said NMR parameter from said at least one compartment of interest;
segmenting said first magnetic resonance image into a plurality of compartments that includes said at least one compartment of interest; and
reconstructing a value of said NMR parameter in said at least one compartment of interest,
wherein said NMR parameter is one of a nuclear spin density, a relaxation time T1, T1ρ, T2, or T2*, a diffusion coefficient, a perfusion measure, a functional measure, a spectral parameter, a chemical reaction rate, or a chemical exchange saturation transfer (CEST) index.

### Claim 2 (depends on 1)

The method of claim 1, wherein said at least one of said set of k-space spatial encoding gradients or coil sensitivity encoding maps is said coil sensitivity encoding maps.

### Claim 3 (depends on 1)

The method of claim 1, wherein said subset of said set of k-space spatial encoding gradients are chosen from a center of k-space.

### Claim 4 (depends on 1)

The method of claim 1, wherein said value of said NMR parameter obtained from said at least one compartment of interest, substantially represents an average value of said NMR parameter in said at least one compartment of interest.

### Claim 5 (depends on 1)

The method of claim 1, wherein said at least one compartment of interest has an irregular shape.

### Claim 6 (depends on 1)

The method of claim 1, further comprising applying said second MRI pulse sequence a plurality of times,
wherein each of said plurality of applications of said second MRI pulse sequence is encoded to cause a corresponding MRI signal to be sensitive to a plurality of parameters selected from a nuclear spin density, a relaxation time T1, T1ρ, T2, or T2*, a diffusion coefficient, a perfusion measure, a functional measure, a spectral parameter, a chemical reaction rate, or a chemical exchange saturation transfer (CEST) index, said corresponding MRI signal thereby being a parameter-sensitive MRI signal.

### Claim 7 (depends on 6)

The method of claim 6, further comprising reconstructing for each of said plurality of applications of said second MRI pulse sequence a corresponding compartment average measure of said parameter-sensitive MRI signal,
wherein each said compartment average measure of the said parameter-sensitive MRI signal is used to determine a compartment average measure of one of a nuclear spin density, a relaxation time T1, T1ρ, T2, or T2*, a diffusion coefficient, a perfusion measure, a functional measure, a spectral parameter, a chemical reaction rate, or a chemical exchange saturation transfer (CEST) index.

### Claim 8 (depends on 6)

The method of claim 6, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a relaxation time is one of a pulse sequence timing parameter.

### Claim 9 (depends on 8)

The method of claim 8, wherein said pulse sequence timing parameter is one of a pulse sequence repetition period, an inversion time, or an echo time.

### Claim 10 (depends on 6)

The method of claim 6, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a diffusion coefficient is a pulsed magnetic field gradient or oscillating magnetic field gradient.

### Claim 11 (depends on 6)

The method of claim 6, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to perfusion is a slice selective MRI pulse applied to one of inflowing or outflowing blood.

### Claim 12 (depends on 6)

The method of claim 6, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a chemical reaction rate is a chemical selective irradiation pulse applied to a chemical specie participating in a corresponding chemical reaction.

### Claim 13 (depends on 6)

The method of claim 6, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a CEST index is a frequency selective saturation NMR pulse with an offset frequency.

### Claim 14 (depends on 13)

The method of claim 13, wherein said MRI signal is corrected for inhomogeneity in a main magnetic field (B0) by a correction process, said correction process comprising:
stacking CEST parameter sensitive MRI data for each offset frequency such that corresponding data sets are aligned in a saturation frequency dimension;
linearly interpolating image k-space data in a saturation frequency domain;
incorporating a regular B0 map into a correction matrix that accounts for spatial and temporal variations in applied magnetic fields; and
reconstructing a compartment-average CEST sensitive parameter for each B0-corrected offset frequency.

### Claim 15 (depends on 13)

The method of claim 13, wherein an additional MRI data set is acquired in which no frequency-selective saturation is applied, and
wherein a CEST sensitive MRI signal at each offset frequency is normalized by dividing by a signal acquired without frequency-selective saturation for said at least one compartment.

### Claim 16

An NMR system for acquiring and reconstructing a value of an NMR parameter spatially localized to at least one compartment of interest, said NMR system employing an applied static magnetic field B0, and NMR excitation and detection systems, and comprising an MRI apparatus configured to accommodate a sample of interest,
wherein said MRI apparatus is configured to:
perform a first magnetic resonance imaging (MRI) of at least a portion of said sample with a first MRI pulse sequence using said NMR system and using at least one of a set of k-space spatial encoding gradients or coil sensitivity encoding maps to obtain a first magnetic resonance image to identify at least one compartment of interest;
generate a second MRI pulse sequence that encodes said NMR parameter with a subset of said at least one of said set of k-space spatial encoding gradients or said coil sensitivity encoding maps;
apply said second MRI pulse sequence using said NMR system to acquire spatial information relating to said NMR parameter from said at least one compartment of interest;
segment said first magnetic resonance image into a plurality of compartments that includes said at least one compartment of interest; and
reconstruct a value of said NMR parameter in said at least one compartment of interest,
wherein said NMR parameter is one of a nuclear spin density, a relaxation time T1, T1ρ, T2, or T2*, a diffusion coefficient, a perfusion measure, a functional measure, a spectral parameter, a chemical reaction rate, or a chemical exchange saturation transfer (CEST) index.

### Claim 17 (depends on 16)

The NMR system of claim 16, wherein said at least one of said set of k-space spatial encoding gradients or coil sensitivity encoding maps is said coil sensitivity encoding maps.

### Claim 18 (depends on 16)

The NMR system of claim 16, wherein said subset of said set of k-space spatial encoding gradients are chosen from a center of k-space.

### Claim 19 (depends on 16)

The NMR system of claim 16, wherein said value of said NMR parameter obtained from said at least one compartment of interest, substantially represents an average value of said NMR parameter in said at least one compartment of interest.

### Claim 20 (depends on 16)

The NMR system of claim 16, wherein said at least one compartment of interest has an irregular shape.

### Claim 21 (depends on 16)

The NMR system of claim 16, further comprising applying said second MRI pulse sequence a plurality of times,
wherein each of said plurality of applications of said second MRI pulse sequence is encoded to cause a corresponding MRI signal to be sensitive to a plurality of parameters selected from a nuclear spin density, a relaxation time T1, T1ρ, T2, or T2*, a diffusion coefficient, a perfusion measure, a functional measure, a spectral parameter, a chemical reaction rate, or a chemical exchange saturation transfer (CEST) index, said corresponding MRI signal thereby being a parameter-sensitive MRI signal.

### Claim 22 (depends on 21)

The NMR system of claim 21, further comprising reconstructing for each of said plurality of applications of said second MRI pulse sequence a corresponding compartment average measure of said parameter-sensitive MRI signal,
wherein each said compartment average measure of the said parameter-sensitive MRI signal is used to determine a compartment average measure of one of a nuclear spin density, a relaxation time T1, T1ρ, T2, or T2*, a diffusion coefficient, a perfusion measure, a functional measure, a spectral parameter, a chemical reaction rate, or a chemical exchange saturation transfer (CEST) index.

### Claim 23 (depends on 22)

The NMR system of claim 22, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a relaxation time is one of a pulse sequence timing parameter.

### Claim 24 (depends on 23)

The NMR system of claim 23, wherein said pulse sequence timing parameter is one of a pulse sequence repetition period, an inversion time, or an echo time.

### Claim 25 (depends on 22)

The NMR system of claim 22, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a diffusion coefficient is a pulsed magnetic field gradient or oscillating magnetic field gradient.

### Claim 26 (depends on 22)

The NMR system of claim 22, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to perfusion is a slice selective MRI pulse applied to one of inflowing or outflowing blood.

### Claim 27 (depends on 22)

The NMR system of claim 22, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a chemical reaction rate is a chemical selective irradiation pulse applied to a chemical specie participating in a corresponding chemical reaction.

### Claim 28 (depends on 22)

The NMR system of claim 22, wherein an agent by which said MRI signal from said second MRI pulse sequence is rendered sensitive to a CEST index is a frequency selective saturation NMR pulse with an offset frequency.

### Claim 29 (depends on 28)

The NMR system of claim 28, wherein said MRI signal is corrected for inhomogeneity in a main magnetic field (B0) by a correction process, said correction process comprising:
stacking CEST parameter sensitive MRI data for each offset frequency such that corresponding data sets are aligned in a saturation frequency dimension;
linearly interpolating image k-space data in a saturation frequency domain;
incorporating a regular B0 map into a correction matrix that accounts for spatial and temporal variations in the applied magnetic fields; and
reconstructing a compartment-average CEST sensitive parameter for each B0-corrected offset frequency.

### Claim 30 (depends on 28)

The NMR system of claim 28, wherein an additional MRI data set is acquired in which no frequency-selective saturation is applied, and
wherein a CEST sensitive MRI signal at each offset frequency is normalized by dividing by a signal acquired without frequency-selective saturation for said at least one compartment.