A novel non-invasive method for using carbon-13 magnetization transfer effects to determine and evaluate in vivo aspartate transaminase (AST) activity and levels in an organ, as a biomarker of disease and certain neurological disorders.

This invention describes a method for non-invasively diagnosing various diseases using magnetic resonance spectroscopy of aspartate transaminase (AST). The diagnostic market is a multi- billion dollar market, with a need for more efficient non-invasive techniques, markers and methods of diagnosis. In particular, this is a novel non-invasive method for using carbon- 13 magnetization transfer effects to determine and evaluate in vivo aspartate transaminase (AST) activity and levels in an organ, including the brain, as a biomarker of disease and certain neurological disorders. This comprises performing in vivo magnetization transfer spectroscopy, and determining the change in magnetic resonance signal intensity of reactants in AST catalyzed reaction. AST activity is known to change as a result of tissue damage and necrosis in a variety of diseases. AST activity is routinely assessed in serum of patients as a non-invasive means of identifying and following up on disease progression. Furthermore, brain levels of AST are altered in certain diseases such as Huntington's Disease, olivopontocerebellar atrophy and epilepsy, but the blood-brain barrier prevents AST from entering serum and being readily measured. Brain AST levels in living patients can be measured by brain biopsies, which are expensive and dangerous. This invention overcomes this problem by measuring AST activity in the brain by using magnetization transfer effect. This can help diagnose or follow up on the progress of a variety of diseases, including Huntington's Disease, olivopontocerebellar atrophy, epilepsy, schizophrenia, as well as hepatitis, cirrhosis, cholangitis, Gilbert's diseases, muscular dystrophy, leukemia, kidney inflammation, cardiac infarction, or the presence of a tumor. Thus, tissue AST activity may become a novel marker of brain disorders which has been inaccessible using current clinical technologies. Applications: Diagnosis and monitoring disease status in a variety of diseases, including Huntington's Disease, olivopontocerebellar atrophy, epilepsy, schizophrenia, as well as hepatitis, cirrhosis, cholangitis, Gilbert's diseases, muscular dystrophy, leukemia, kidney inflammation, cardiac infarction, or the presence of a tumor. Market: The diagnostic market is a multi-billion dollar market, with a need for more efficient non-invasive techniques, markers and new methods of diagnosis. Publication: J Shen. In vivo carbon-13 magnetization transfer effect: detection of aspartate aminotransferase reaction. Magn Reson Med. 2005 Dec; 54(6):1321-1326.

U.S. Patent Application No. 11/356,214 filed 21 Feb 2006 (HHS Reference No. E-231-2005/0-US-02) Inventor: Dr. Jun Shen (NIMH)

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