Magnetic resonance method for assesing amide proton transfer effects between amide protons of endogenous mobile proteins and peptides and tissue water in situ and its use for imaging ph and mobile protein/peptide content

A method for determining an effect of amide proton transfer between amide protons of endogenous mobile proteins/peptides and water protons as measured by one of MRI or NMR spectroscopy or spectroscopic imaging, said effect being reflected in one of amide proton content, amide proton exchange properties or mobile protein/peptide content, said method comprising the steps of:

• irradiating a pool of amide protons of said mobile protons and peptides that is in exchange with a pool of water protons to label the amide protons if said pool if amide protons and measuring the effect on the water protons;
• determining an amide proton transfer (APT) effect corresponding to the transfer of saturation between said pool of amide protons and said pool of water protons;
• establishing a relationship between proton transfer effect of amide protons and said one of amide proton content, cellular pH or pH effects;
• and
• determining a magnitude of one of labile amide proton content, mobile protein/peptide content, pH or pH effects from the determined amide proton transfer effect and the established relationship.

A method for magnetic resonance imaging comprising the steps of:

• acquiring MR image data of a spatial region of interest;
• assessing a magnitude of or a change in one of labile amide proton content, mobile protein/peptide content or pH of endogenous or exogenous tissue the region of interest using a 1H saturation transfer technique;
• and
• adjusting contrast of the acquired MR image data based on said assessing so the adjusted acquired MR image data reflects relative differences of said one of labile amide proton content, protein/peptide content, or pH between spatial areas, tissues, and the like within the spatial region of interest.

A method of MRI comprising the steps of:

• acquiring MR image data that includes:
• placing one of a sample or subject of interest in a MRI scanner,
• selectively exciting MR signal in at least one spatial region of said sample or subject, and
• detecting signals from said spatial region to generate image data;
• assessing one of labile amide proton content of mobile endogenous proteins/peptides, mobile protein/peptide content or pH of said at least one spatial region of said sample or subject using a 1H saturation transfer technique;
• and
• adjusting the generated MRI image data based on said assessing so the adjusted generated MR image data reflects relative differences of said one of labile amide proton content, mobile protein/peptide content or pH between spatial areas, tissues, and the like within said at least one spatial region.

A method for relating amide proton exchange properties to tissue pH, comprising the steps of:

• irradiating a pool of amide protons of mobile endogenous proteins/peptides that is in exchange with a pool of water protons to label the amide protons of said pool of amide protons and measuring the effect on the water protons the amide protons are in exchange with;
• determining an amide proton transfer effect corresponding to the transfer of saturation between said pool of amide protons and said pool of protons;
• and
• determining tissue pH or pH effects of spatial areas, tissues and the like being subjected to said irradiation from the determined amide proton transfer effect.

A method for relating a water proton signal intensity to protein and peptide content, comprising the steps of:

• irradiating an endogenous pool of amide protons of mobile endogenous proteins/peptides that is in exchange with a pool of water protons to label the amide protons of said pool of amide protons and measuring the effect on the water protons the amide protons are in exchange with;
• determining a or change in an amide proton transfer effect corresponding to the transfer of saturation between said pool of amide protons and said pool of water protons for spatial areas, tissues and the like being subjected to irradiating;
• and
• determining the protein and peptide content from the determined amide proton transfer effect on the water signal intensity.

A method for relating a water proton signal intensity to protein and peptide content, comprising the steps of:

• irradiating an endogenous pool of amide protons of mobile endogenous proteins/peptides that is in exchange with a pool of water protons to label the amide protons of said pool of amide protons and measuring the effect on the water protons the amide protons are in exchange with;
• determining a magnitude of an amide proton transfer effect corresponding to the transfer of saturation between said pool of amide protons and said pool of water protons for spatial areas, tissues and the like being subjected to said irradiating;
• and
• determining the protein and peptide content from the determined amide proton transfer effect on the water signal intensity.

A method for imaging labile amide proton content and properties via exchange relationship of amide protons with the water signal, said method comprising the steps of:

• irradiating an endogenous pool of amide protons of mobile endogenous proteins/peptides that is in exchange with a pool of water protons to label the amide protons of said pool of amide protons and measuring the effect on the water protons the amide protons are in exchange with;
• determining an amide proton transfer effect corresponding to the transfer of saturation between said pool of amide protons and said pool of water protons;
• and
• determining a change in one of labile amide proton content, mobile protein/peptide content, cellular pH or pH effects from the determined amide proton transfer effect for spatial areas, tissues and the like being subjected to said irradiating.

A method for imaging labile amide proton content and properties via exchange relationship of amide protons with the water signal, said method comprising the steps of:

• irradiating an endogenous pool of amide protons of mobile endogenous proteins/peptides that is in exchange with a pool of water protons to label the amide protons of said pool of amide protons and measuring the effect on the water protons the amide protons are in exchange with;
• determining an amide proton transfer effect corresponding to the transfer of saturation between said pool of amide protons and said pool of water protons;
• and
• determining a magnitude of one of labile amide proton content, mobile protein/peptide content, cellular pH or pH effects from the determined amide proton transfer effect for spatial areas, tissues and the like being subjected to said irradiating.