Method for enhancing contrast produced by MRI

Abstract

A method for obtaining an image by MRI, comprising: administering at least one contrast agent to a subject in amounts effective to perform CEDST MRI analysis; and performing CEDST MRI analysis to produce an image of the subject. A number of different contrast agents can be used to practice the present method including, without limitation, sugars, amino acids, nitrogen-containing heterocycles, purines and pyrimidines, nucleosides; imidazole and derivatives thereof, imino acids, barbituric acid and analogs thereof, and miscellaneous materials, such as guanidine hydantoin, parabanic acid, and biologically active salts thereof.

1 - 42 . (canceled) 
     
     
         43 : A method for determining pH by CEDST MRI, comprising:
 determining by CEDST MRI analysis a ratio of (M O −M S ) Site 1 /(M O −M S ) Site 2  for a contrast agent having two exchangeable protons; and   comparing the (M O −M S ) Site 1 /(M O −M S ) Site 2  ratio to a standard curve to determine pH.   
     
     
         44 : The method according to  claim 43  where the contrast agent is dihydrouracil. 
     
     
         45 : The method according to  claim 43  where the contrast agent is administered as an aqueous composition. 
     
     
         46 : The method according to  claim 45  where the composition comprises about 62.5 mM contrast agent. 
     
     
         47 : The method according to  claim 43  where the standard curve is prepared by:
 selecting a contrast agent having two different exchangeable protons to perform CEDST MRI in vivo analysis as a function of pH;   performing CEDST MRI in vitro analysis as a function of pH using the contrast agent; and   plotting ratios of (M O −M S ) Site  1/(M O −M S ) Site 2  to obtain a standard curve.   
     
     
         48 : A method for determining pH of physiological tissues in vivo, comprising:
 selecting a contrast agent having two different exchangeable protons to perform CEDST MRI in vitro analysis as a function of pH;   performing CEDST MRI in vitro analysis as a function of pH using the contrast agent;   plotting ratios of (M O −M S ) Site  1/(M O −M S ) Site 2  to obtain a standard curve;   administering the contrast agent to a subject;   allowing the contrast agent sufficient time to locate in tissue of interest;   determining in vivo by CEDST MRI analysis a ratio of (M O −M S ) Site  1/(M O −M S ) Site 2  using the contrast agent; and   comparing the (M O −M S ) Site  1/(M O −M S ) Site 2  ratio to a standard curve to determine pH of the tissue.   
     
     
         49 : The method according to  claim 48  where the contrast agent is dihydrouracil. 
     
     
         50 : A method for performing MRI analysis, comprising:
 administering an amino acid to a subject in amounts effective to perform CEDST MRI;   performing CEDST MRI analysis on the subject.   
     
     
         51 : The method according to  claim 50  where the contrast agent is 5-hydroxy tryptophan. 
     
     
         52 : A method for determining physiological temperature, comprising:
 performing CEDST MRI analysis in vivo; and   comparing in vivo CEDST MRI results to a standard curve to determine physiological temperature.   
     
     
         53 : The method according to  claim 52  where the standard curve is made by:
 selecting one or more contrast agents with a single exchangeable proton to perform CEDST MRI in vitro analysis as a function of temperature;   performing CEDST MRI in vitro analysis as a function of temperature using the one or more contrast agents; and   line-fitting a shape of the entire ST spectrum or a portion thereof relative to temperature and generating a temperature calibration curve.   
     
     
         54 : The method according to  claim 52  where the contrast agent is barbituric acid. 
     
     
         55 - 59 . (canceled) 
     
     
         60 : A method for determining pH by CEDST MRI, comprising:
 determining by CEDST MRI analysis a ratio of M S   Site 2 (M O −M S ) Site 1 /[M S   Site 1 (M O −M S ) Site 2 ] for one or more contrast agents having two exchangeable protons; and   comparing the M S   Site 2 (M O −M S ) Site 1 /[M S   Site 1 (M O −M S ) Site 2 ] ratio to a standard curve to determine pH.   
     
     
         61 : The method according to  claim 60  where the one or more contrast agents is selected from the group consisting of 5,6-dihydrouracil, 5-hydroxy-tryptophan and 2-imidzaolidinethione, polymers thereof, and mixtures thereof. 
     
     
         62 : The method according to  claim 60  where the one or more contrast agents is administered as an aqueous composition. 
     
     
         63 : The method according to  claim 62  where the composition comprises about 62.5 mM of the one or more contrast agents. 
     
     
         64 : The method according to  claim 43  where the standard curve is prepared by:
 selecting one or more contrast agents having two different exchangeable protons to perform CEDST MRI in vivo analysis as a function of pH;   performing CEDST MRI in vitro analysis as a function of pH using the one or more contrast agents; and   plotting ratios of M S   Site 2 (M O −M S ) Site 1 /[M S   Site 1 (M O −M S ) Site 2 ] to obtain a standard curve.   
     
     
         65 : A method for determining pH of physiological tissues in vivo, comprising:
 selecting one or more contrast agents having two different exchangeable protons to perform CEDST MRI in vitro analysis as a function of pH;   performing CEDST MRI in vitro analysis as a function of pH using the contrast agent;   plotting ratios of M S   Site 2 (M O −M S ) Site 1 /[M S   Site 1 (M O −M S ) Site 2 ] to obtain a standard curve;   administering the one or more contrast agents to a subject;   allowing the one or more contrast agents sufficient time to locate in tissue of interest;   determining in vivo by CEDST MRI analysis a ratio of M S   Site 2 (M O −M S ) Site 1 /[M S   Site 1 (M O −M S ) Site 2 ] using the one or more contrast agents; and   comparing the M S   Site 2 (M O −M S ) Site 1 /[M S   Site 1 (M O −M S ) Site 2 ] ratio to a standard curve to determine pH of the tissue.   
     
     
         66 : The method according to  claim 65  where the one or more contrast agents is selected from the group consisting of 5,6-dihydrouracil, 5-hydroxy-tryptophan and 2-imidzaolidinethione, polymers thereof, and mixtures thereof. 
     
     
         67 : A composition for analyzing tissues and physiological conditions by CEDST MRI, comprising an aqueous mixture of at least one contrast agent in amounts sufficient to perform CEDST MRI analysis, the contrast agent being selected from the group consisting of sugars and oligomers and polymers thereof, amino acids and oligomers and polymers thereof, nitrogen-containing heterocycles, nucleosides, imidazole and derivatives thereof, imino acids and analogs thereof, barbituric acid and analogs thereof, guanidine, hydantoin, parabanic acid, biologically active salts of the contrast agents, and mixtures of contrast agents. 
     
     
         68 : The composition of  claim 67  wherein the contrast agent is selected from the group consisting of mannitol, sorbitol, fructose, dextrose, galactose, sucrose, maltose, lactose, and mixtures thereof. 
     
     
         69 : The composition of  claim 67  wherein the contrast agent is selected from the group consisting of alanine, arginine, lysine, glutamine, tryptophan, and mixtures thereof. 
     
     
         70 : The composition of  claim 67  wherein the contrast agent is 5-hydroxy-tryptophan. 
     
     
         71 : The composition of  claim 67  further comprising a physiologically acceptable carrier.