US 6,617,169 B2Granted

Two-dimensional MR spectroscopy techniques

AssigneeThe McLean Hospital Corporation

InventorsYong Ke, Perry F. Renshaw, Bruce Cohen

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Abstract

The invention features methods of selecting chemical peaks from two-dimensional magnetic resonance spectra for one-dimensional extraction and quantification methods using these one-dimensional extractions. The methods permit enhanced differentiation of particular peaks in two-dimensional magnetic resonance spectroscopy and allow for quantification of chemical concentrations in test samples, such as human brain tissue, having complex magnetic resonance spectra due to the presence of numerous chemicals. These new techniques can be used to provide information about the concentrations of a variety of chemicals, including metabolites, in both biological and non-biological media.

Claims19

Dependent claims

A method for obtaining a relative measure of concentrations of metabolites in vivo comprising:

(a) subjecting a first reference sample comprising a known concentration of a first metabolite and a known concentration of a reference metabolite to a magnetic resonance spectroscopy sequence;
(b) obtaining a two-dimensional magnetic resonance spectrum of the first reference sample;
(c) extracting a one-dimensional magnetic resonance slice comprising a peak for the first metabolite and a peak for the reference metabolite, wherein the peak M the first metabolite is identified by comparing peaks in the two-dimensional magnetic resonance spectrum of the first reference sample to select a peak that is substantially distinct from other peaks in the two-dimensional magnetic resonance spectrum;
(d) calculating a correlation factor for the first metabolite, wherein the correlation factor is a ratio of a peak integral for the first metabolite to a peak integral for the reference metabolite, multiplied by a ratio of the concentration of the reference metabolite to the concentration of the first metabolite;
(e) subjecting a second reference sample comprising a known concentration of a second metabolite and a known concentration of the reference metabolite to the magnetic resonance spectroscopy sequence;
(f) obtaining a two-dimensional magnetic resonance spectrum of the second reference sample;
(g) extracting a one-dimensional magnetic resonance slice comprising a peak for the second metabolite and a peak for the reference metabolite, wherein the peak for the second metabolite is identified by comparing peaks in the two-dimensional magnetic resonance spectrum of the second reference sample to select a peak that is substantially distinct from other peaks in the two-dimensional magnetic resonance spectrum;
(h) calculating a correlation factor for the second metabolite, wherein the correlation factor is a ratio of a peak integral for the second metabolite to a peak integral the reference metabolite multiplied by a ratio of the concentration of the reference metabolite to the concentration of the second metabolite;
(i) calculating a comparison ratio, wherein the comparison ratio is the ratio of the correlation factor for the second metabolite in the second reference sample to the correlation factor for the first metabolite in the first reference sample;
(j) subjecting a test sample comprising the first metabolite and the second metabolite to the magnetic resonance spectroscopy sequence;
(k) obtaining a two-dimensional magnetic resonance spectrum of the test sample;
(l) extracting a one-dimensional magnetic resonance slice front the two-dimensional magnetic resonance spectrum of the test sample comprising the peak for the first metabolite;
(m) extracting a one-dimensional magnetic resonance slice from the two-dimensional magnetic resonance spectrum of the test sample comprising the peak for the second metabolite;
(n) calculating a test sample ratio, wherein the test sample ratio is the ratio of a peak integral or the second metabolite in the extracted one-dimensional slice for the second metabolite in the test sample to a peak integral of the first metabolite in the extracted one-dimensional slice for the first metabolite in the test sample;
and
(o) obtaining a relative measure of the concentration of the second metabolite in the test sample compared to the concentration of the first metabolite in the test sample by dividing the test sample ratio by the comparison ratio.

13 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/823,613Filed 30 Mar 2001
Published: US 2002/0142367 A13 Oct 2002
Granted: 9 Sep 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

G01R 33/4633
NMR spectroscopy: sequences for multi-dimensional NMR
G01N 33/9426
Neurotransmitters: gABA, i.e. gamma-amino-butyrate
G01N 33/946
Involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors: cNS-stimulants, e.g. cocaine, amphetamines
Y10T 436/24
Chemistry: analytical and immunological testing: nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

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US 2002/0142367 A1Pre-grant publication · published 3 Oct 2002
US 6,617,169 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A method for obtaining a relative measure of concentrations of metabolites in vivo comprising:

(a) subjecting a first reference sample comprising a known concentration of a first metabolite and a known concentration of a reference metabolite to a magnetic resonance spectroscopy sequence;
(b) obtaining a two-dimensional magnetic resonance spectrum of the first reference sample;
(c) extracting a one-dimensional magnetic resonance slice comprising a peak for the first metabolite and a peak for the reference metabolite, wherein the peak M the first metabolite is identified by comparing peaks in the two-dimensional magnetic resonance spectrum of the first reference sample to select a peak that is substantially distinct from other peaks in the two-dimensional magnetic resonance spectrum;
(d) calculating a correlation factor for the first metabolite, wherein the correlation factor is a ratio of a peak integral for the first metabolite to a peak integral for the reference metabolite, multiplied by a ratio of the concentration of the reference metabolite to the concentration of the first metabolite;
(e) subjecting a second reference sample comprising a known concentration of a second metabolite and a known concentration of the reference metabolite to the magnetic resonance spectroscopy sequence;
(f) obtaining a two-dimensional magnetic resonance spectrum of the second reference sample;
(g) extracting a one-dimensional magnetic resonance slice comprising a peak for the second metabolite and a peak for the reference metabolite, wherein the peak for the second metabolite is identified by comparing peaks in the two-dimensional magnetic resonance spectrum of the second reference sample to select a peak that is substantially distinct from other peaks in the two-dimensional magnetic resonance spectrum;
(h) calculating a correlation factor for the second metabolite, wherein the correlation factor is a ratio of a peak integral for the second metabolite to a peak integral the reference metabolite multiplied by a ratio of the concentration of the reference metabolite to the concentration of the second metabolite;
(i) calculating a comparison ratio, wherein the comparison ratio is the ratio of the correlation factor for the second metabolite in the second reference sample to the correlation factor for the first metabolite in the first reference sample;
(j) subjecting a test sample comprising the first metabolite and the second metabolite to the magnetic resonance spectroscopy sequence;
(k) obtaining a two-dimensional magnetic resonance spectrum of the test sample;
(l) extracting a one-dimensional magnetic resonance slice front the two-dimensional magnetic resonance spectrum of the test sample comprising the peak for the first metabolite;
(m) extracting a one-dimensional magnetic resonance slice from the two-dimensional magnetic resonance spectrum of the test sample comprising the peak for the second metabolite;
(n) calculating a test sample ratio, wherein the test sample ratio is the ratio of a peak integral or the second metabolite in the extracted one-dimensional slice for the second metabolite in the test sample to a peak integral of the first metabolite in the extracted one-dimensional slice for the first metabolite in the test sample;
and
(o) obtaining a relative measure of the concentration of the second metabolite in the test sample compared to the concentration of the first metabolite in the test sample by dividing the test sample ratio by the comparison ratio.

13 more elements

Facts

Application

09/823,613Filed 30 Mar 2001

Published

US 2002/0142367 A13 Oct 2002

Granted

9 Sep 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

G01R 33/4633
NMR spectroscopy: sequences for multi-dimensional NMR
G01N 33/9426
Neurotransmitters: gABA, i.e. gamma-amino-butyrate
G01N 33/946
Involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors: cNS-stimulants, e.g. cocaine, amphetamines
Y10T 436/24
Chemistry: analytical and immunological testing: nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry