Magnetic resonance imaging
Assignee1C Targets AS
InventorsPer Jynge, Arne Skjold, Henrik W. Larsson
Life of this patent
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Abstract
A method of determining the amount of intracellular manganese in the myocardium of an individual pre-administered with a manganese contrast agent, or a pharmaceutically acceptable salt thereof, comprising subjecting, the individual to a MRI procedure to assess the signal intensity (SI) of images, or more preferably the longitudinal relaxation rate, R1 throughout the myocardium.
Claims32
A method of diagnosing cardiac remodeling and likelihood of arrhythmias and of heart failure, by a single examination in a human individual weeks to months after said individual has suffered an acute myocardial infarction, said method consisting of four consecutive steps:
- (i) administering intravenously to said individual a manganese contrast agent capable of releasing manganese ions or an intact manganese contrast agent, or pharmaceutically acceptable salts thereof, for enabling uptake of manganese in cardiomyocytes of said individual;
- (ii) thereafter subjecting said individual to one MRI procedure measuring a longitudinal relaxation rate, R1, or its reciprocal a longitudinal relaxation time, T1, throughout sectors and layers of the myocardium and expressing the measured R1 or T1 values in maps of said myocardium;
- (iii) detecting the presence of a continuous gradient of R1 or T1 in the myocardium from a site of infarction to a region remote from said site, wherein the R1 values correlate positively and the T1 values correlate negatively to the function and viability of cardiomyocytes;
- and
- (iv) diagnosing the individual with cardiac remodeling and likelihood of arrhythmias and heart failure when the presence of said continuous gradient in R1 or T1 is detected;
- wherein the step (iii) comprises:
- (a) determining whether the R1 values of the sectors or layers exhibit the continuous gradient from subnormal values at a site of infarction to supernormal values at a region remote from said site, wherein the R1 values correlate positively to the function and viability of cardiomyocytes;
- or
- (b) determining whether the T1 values of the sectors or layers exhibit the continuous gradient from supernormal values at a site of infarction to subnormal values at a region remote from said site, wherein the T1 values correlate negatively to the function and viability of cardiomyocytes.
A method of diagnosing cardiac remodeling and likelihood of arrhythmias and of heart failure, by a single examination in a human individual weeks to months after said individual has suffered an acute myocardial infarction, said method consisting of four consecutive steps:
- (i) administering intravenously to said individual a manganese contrast agent capable of releasing manganese ions or an intact manganese contrast agent, or pharmaceutically acceptable salts thereof, for enabling uptake of manganese in cardiomyocytes of said individual;
- (ii) thereafter subjecting said individual to one MRI procedure measuring a signal intensity in R1 weighted images throughout sectors and layers of the myocardium and expressing the measured signal intensity in images of said myocardium;
- (iii) detecting the presence of a continuous gradient of signal intensity in the myocardium from a site of infarction to a region remote from said site, wherein the signal intensity correlates positively to the function and viability of cardiomyocytes;
- and
- (iv) diagnosing the individual with cardiac remodeling and likelihood of arrhythmias and heart failure when the presence of said continuous gradient in signal intensity is detected;
- wherein the step (iii) comprises determining whether the signal intensity of the sectors or layers exhibit the continuous gradient from subnormal values at a site of infarction to supernormal values at a region remote from said site.
A method of detecting a continuous gradient of a longitudinal relaxation rate or a longitudinal relaxation time in a myocardium from a site of infarction to a region remote from said site in a human individual in a single examination, said method consisting of:
- (i) administering intravenously over 1 to 30 minutes a dose of 0.5 to 40 μmol/kg body weight of a chelated manganese contrast agent capable of releasing manganese ions with a Ka value in the range of 107 to 1025, or a pharmaceutically acceptable salt thereof, to said individual weeks to months after said individual has suffered an acute myocardial infarction;
- (ii) subjecting said individual to one MRI procedure measuring a longitudinal relaxation rate, R1, or its reciprocal the longitudinal relaxation time, T1, throughout sectors and layers of the myocardium of said individual and expressing the measured R1 or T1 values in maps of said myocardium;
- (iii) dividing the maps of R1 or T1 into transmural sectors or layers to create a composite distribution plot of R1 or T1;
- (iv) detecting the presence of the continuous gradient of the R1 or T1 values of the sectors or layers in the myocardium from a site of infarction to a region remote from said site, wherein the R1 values correlate positively or the T1 values correlate negatively to the function and viability of cardiomyocytes;
- and
- (v) diagnosing the individual with cardiac remodeling and an increased risk of arrhythmia or heart failure when the presence of said continuous gradient in R1 or T1 is detected;
- wherein the step (iv) comprises:
- (a) determining whether the R1 values of the sectors or layers exhibit the continuous gradient from subnormal values at a site of infarction to supernormal values at a region remote from said site, wherein the R1 values correlate positively to the function and viability of cardiomyocytes;
- or
- (b) determining whether the T1 values of the sectors or layers exhibit the continuous gradient from supernormal values at a site of infarction to subnormal values at a region remote from said site, wherein the T1 values correlate negatively to the function and viability of cardiomyocytes.
A method of assessing the risk of arrhythmias or heart failure in an individual, examined weeks to months after suffering an acute myocardial infarction, by subjecting said individual to a single diagnostic procedure to determine the presence and extent of remodeling of myocardium, said method consisting of the following four steps:
- (i) administering intravenously a manganese contrast agent capable of releasing manganese ions or an intact manganese chelate contrast agent for cardiomyocyte uptake, or a pharmaceutically acceptable salt thereof, to said individual;
- (ii) subjecting said individual to an MRI procedure to determine viability and function of cardiomyocytes by measuring a longitudinal relaxation rate, R1, or its reciprocal a longitudinal relaxation time, T1, throughout sectors and layers of the myocardium and mapping the measured R1 or T1 values throughout said myocardium;
- (iii) detecting remodeling of myocardium by observing a continuous gradient of R1 or T1 in the myocardium from a site of infarction to a region remote from said site wherein the R1 values correlate positively and the T1 values correlate negatively to the function and viability of cardiomyocytes;
- and
- (iv) quantifying the extent of remodeling and the risk of arrhythmias or heart failure by measuring the continuous gradient in R1 or T1;
- wherein the step (iii) comprises:
- (a) determining whether the R1 values of the sectors or layers exhibit the continuous gradient from subnormal values at a site of infarction to supernormal values at a region remote from said site, wherein the R1 values correlate positively to the function and viability of cardiomyocytes;
- or
- (b) determining whether the T1 values of the sectors or layers exhibit the continuous gradient from supernormal values at a site of infarction to subnormal values at a region remote from said site, wherein the T1 values correlate negatively to the function and viability of cardiomyocytes.
Dependencies are inferred from the claim text.