US5201311A
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Spatially-localized chemical-reaction-rate NMR spectroscopic imaging
Assignee: General Electric Co
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Filing: 1992-08-10
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Granted: 1993-04-13
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Expires: 2012-08-10
Abstract
Abstract A method for providing information about the rate of a selected chemical reaction in each of at least one selected volume elements (voxels) in a sample includes the steps of: exciting a reaction-rate-dependent chemical-shift spectrum, by a selected stimulus (such as one of saturation-transfer and inversion-transfer RF signal pulses) to label the NMR signal of a first reaction constituent; spatially localizing the NMR response signal, provided by the excited resonance, to a selected voxel within the sample; and acquiring and processing the NMR response data from the localized voxel. The excitation, localization and data acquisition subsequences are repeated to generate data substantially proportional, or equal, to the reaction rate constants in the selected voxels, and in planes and/or volumes thereof.
Inventors
- 👤 Paul A. Bottomley
- 👤 Christopher J. Hardy
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 10:08
CPC Classifications
G; G01; G01R; G01R33/00; G01R33/20; G01R33/44; G01R33/48; G01R33/483; G01R33/485
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
253 words
A method for providing information about a rate of a selected chemical reaction in each of at least one selected voxel of a sample, comprising the steps of: (a) immersing the sample having at least a first reaction constituent and a second reaction constituent in a static magnetic field; (b) labeling the second reaction constituent by applying a chemically-selective RF stimulus to the sample in the absence of a magnetic field gradient, said labeling including the step of substantially inverting resonance magnetization from the second reaction constituent, the chemically-selective RF stimulus being an RF pulse having a frequency substantially centered at a selected characteristic peak of an NMR chemical shift spectrum of the second reaction constituent, and having a bandwidth substantially the width of the selected characteristic peak; (c) exciting an NMR response signal from the first constituent resonance, and spacially localizing the NMR response signal to a desired one of the at least one selected voxel; (d) acquiring and storing data characterizing a magnetization amplitude M A of the NMR response signal from the desired voxel; (e) substantially inverting a complementary control portion of the NMR spectrum of the second reaction constituent, with respect to the resonance of the second reaction constituent, and (f) repeating the steps (c) and (d), for the same desired voxel, to obtain data characterizing an inverted magnetization amplitude M' 0A ; and (g) calculating from the M A and M' 0A data a quantity substantially proportionate to a reaction rate constant k A in that desired voxel.
Claim 2
Independent Claim
253 words
A method for providing information about a rate of a selected chemical reaction in each of at least one selected voxel of a sample, comprising the steps of: (a) immersing the sample having at least a first reaction constituent and a second reaction constituent in a static magnetic field; (b) labeling the second reaction constituent by applying a chemically-selective RF stimulus to the sample in the absence of a magnetic field gradient, said labeling including the step of substantially inverting resonance magnetization from the second reaction constituent, the chemically-selective RF stimulus being an RF pulse having a frequency substantially centered at a selected characteristic peak of an NMR chemical shift spectrum of the second reaction constituent, and having a bandwidth substantially the width of the selected characteristic peak; (c) exciting an NMR response signal from the first constituent resonance, and spacially localizing the NMR response signal to a desired one of the at least one selected voxel; (d) acquiring and storing data characterizing a magnetization amplitude M A of the NMR response signal from the desired voxel; (e) substantially inverting a complementary control portion of the NMR spectrum of the second reaction constituent, with respect to the resonance of the second reaction constituent, and (f) repeating the steps (c) and (d), for the same desired voxel, to obtain data characterizing an inverted magnetization amplitude M' 0A ; and (g) calculating from the M A and M' 0A data a quantity substantially proportionate to a reaction rate constant k A in that desired voxel.
Claim 3
Dependent Claim
43 words
The method of claim 1 wherein the step of labeling the second reaction constituent comprises the step of applying an RF pulse having a frequency and bandwidth that substantially avoids inversion of major peaks of the NMR spectrum of the first reaction constituent.
Claim 4
Independent Claim
259 words
A method for providing information about a rate of a selected chemical reaction in each of at least one selected voxel of a sample, comprising the steps of: (a) immersing the sample having at least a first reaction constituent and a second reaction constituent in a static magnetic field; (b) labeling the second reaction constituent by applying a chemically-selective RF stimulus to the sample in the absence of a magnetic field gradient, said labeling including the step of substantially saturating a resonance of the second reaction constituent, the chemically-selective RF stimulus being an RF pulse having a frequency substantially centered at a selected characteristic peak of an NMR chemical shift spectrum of the second reaction constituent, and having a bandwidth substantially the width of the selected characteristic peak; (c) exciting an NMR response signal from the first reaction constituent resonance, and spacially localizing the NMR response signal to a desired one of the at least one selected voxel; (d) acquiring and storing data characterizing a magnetization amplitude M A of the NMR response signal from the desired voxel; (e) substantially saturating the resonance of the second reaction constituent with an RF stimulus having a frequency matching a complementary control portion of the NMR spectrum of the second reaction constituent, and (f) repeating the steps (c) and (d), for the same desired voxel, to obtain data characterizing an saturation magnetization amplitude M' 0A ; and (g) calculating from the M A and M' 0A data a quantity substantially proportionate to a reaction rate constant k A in that desired voxel.
Claim 5
Independent Claim
259 words
A method for providing information about a rate of a selected chemical reaction in each of at least one selected voxel of a sample, comprising the steps of: (a) immersing the sample having at least a first reaction constituent and a second reaction constituent in a static magnetic field; (b) labeling the second reaction constituent by applying a chemically-selective RF stimulus to the sample in the absence of a magnetic field gradient, said labeling including the step of substantially saturating a resonance of the second reaction constituent, the chemically-selective RF stimulus being an RF pulse having a frequency substantially centered at a selected characteristic peak of an NMR chemical shift spectrum of the second reaction constituent, and having a bandwidth substantially the width of the selected characteristic peak; (c) exciting an NMR response signal from the first reaction constituent resonance, and spacially localizing the NMR response signal to a desired one of the at least one selected voxel; (d) acquiring and storing data characterizing a magnetization amplitude M A of the NMR response signal from the desired voxel; (e) substantially saturating the resonance of the second reaction constituent with an RF stimulus having a frequency matching a complementary control portion of the NMR spectrum of the second reaction constituent, and (f) repeating the steps (c) and (d), for the same desired voxel, to obtain data characterizing an saturation magnetization amplitude M' 0A ; and (g) calculating from the M A and M' 0A data a quantity substantially proportionate to a reaction rate constant k A in that desired voxel.
Claim 6
Dependent Claim
43 words
The method of claim 3 wherein the step of labeling the second reaction constituent comprises the step of applying an RF pulse having a frequency and bandwidth that substantially avoids saturation of major peaks of the NMR spectrum of the first reaction constituent.
Claim 7
Dependent Claim
22 words
The method of claim 3, further comprising the step of repeating steps (b)-(g) for at least one other voxel in the sample.
Claim 8
Dependent Claim
26 words
The method of claim 5, further comprising the step of providing data for a plurality of voxels all located in a single plane of the sample.
Claim 9
Dependent Claim
26 words
The method of claim 5, further comprising the step of providing data for a plurality of voxels all located in a selected volume of the sample.
Claim 10
Dependent Claim
46 words
The method of claim 3, further comprising the steps of: acquiring an image of the sample having a plurality of voxels; and superimposing upon each voxel of the sample image a selected one of the an intensity representing reaction rate constant k A for that voxel.
Claim 11
Dependent Claim
24 words
The method of claim 3, wherein the sample is a portion of a living organism, and the selected chemical reaction is a metabolic reaction.
Claim 12
Dependent Claim
13 words
The method of claim 9, wherein the metabolic reaction is a creatine-kinase reaction.
Claim 13
Dependent Claim
75 words
The method of claim 3, wherein the reaction-rate k A constant is calculated from k A =(1-R·M A /M 0A )/T' 1A where R is a factor accounting for the use of a NMR repetition time interval T R which will not permit full T 1 relaxation of the magnetization of reactant A, and T' 1A is the T 1 relaxation time constant of the reactant A in the presence of irradiation of readout B.
Claim 14
Dependent Claim
16 words
The method of claim 11, wherein a value of T' 1A is measured in each voxel.
Claim 15
Dependent Claim
15 words
The method of claim 11, wherein a spatially-averaged average value of T' 1A is used.
Claim 16
Dependent Claim
71 words
The method for providing information about a rate of a selected chemical reaction of claim 3 wherein step (c) comprises the step of applying at least one spatially selected RF stimulus with an NMR flip-angle of less than or substantially comparable to 90° applied in the presence of a first magnetic field gradient pulse, followed by a second gradient pulse having polarity opposite that of the first magnetic field gradient pulse.
Claim 17
Dependent Claim
60 words
The method for providing information about a rate of a selected chemical reaction of claim 3 wherein step (c) comprises the step of applying at least one spatially RF inversion pulse applied in the presence of a magnetic field gradient pulse followed by a substantially non-selective RF stimulus having an NMR flip-angle of less than or substantially comparable to 90°.
Claim 18
Dependent Claim
73 words
The method of claim 3 wherein step (c) comprises the steps of: (c1) applying an RF stimulus to the sample to excite an NMR response signal from at least the first reaction constituent in the sample; and (c2) applying a phase-encoding magnetic field gradient pulse in at least one spatial dimension in order to spatially localize the NMR response signal from at least the first reaction constituent to at least one desired voxel.
Claim 19
Dependent Claim
46 words
The method for providing information about a rate of a selected chemical reaction of claim 16 wherein step (c1) comprises the step of applying an RF stimulus having an amplitude and duration chosen to produce an NMR flip-angle of less than or substantially comparable to 90°.
Claim 20
Dependent Claim
35 words
The method for providing information about a rate of a selected chemical reaction of claim 16 wherein step (c2) comprises the step of applying three phase-encoding magnetic gradients pulses in three substantially orthogonal spatial dimensions.
Claim 21
Dependent Claim
83 words
The method of claim 3 wherein step (c) comprises the steps of: (c1) applying a spatially selective RF stimulus to the sample to excite an NMR response signal from at least the first reaction constituent localized in at least one spatial dimension in the sample; and (c2) applying a phase-encoding magnetic field gradient pulse in at least a second spatial dimension in order to spatially localize the NMR response signal from at least the first reaction constituent to at least one desired voxel.
Claim 22
Dependent Claim
58 words
The method for providing information about a rate of a selected chemical reaction of claim 19 wherein the step (c1) comprises the step of applying a time-changing, at least two-dimensional spatially selective pulse in the presence of a magnetic field gradient pulse to create a magnetic field gradient whose direction is reoriented in two spatial dimensions over time.
Claim 23
Dependent Claim
33 words
The method for providing information about a rate of a selected chemical reaction of claim 19 further comprising the step of applying a phase-encoding magnetic field gradient pulse in a third spatial dimension.
Claim 24
Dependent Claim
59 words
The method of providing information about a rate of a selected chemical reaction of claim 19 wherein step (c1) comprises the step of applying at least one spatially selective excitation pulse having an NMR flip-angle less than or substantially comparable to 90° in the presence of a magnetic field gradient pulse, followed by a gradient pulse of opposite polarity.
Claim 25
Dependent Claim
39 words
The method for providing information about a rate of a selected chemical reaction of claim 19 wherein step (b) comprises applying an RF stimulus having a sinc pulse shape having an amplitude defined by: sin(t)/t where t is time.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-04-12 | 1996-10-12 | 1997-04-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-04-12 | 2000-10-12 | 2001-04-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-04-12 | 2004-10-12 | 2005-04-13 | $7700.00 | Window Closed / Lapsed |