# US 2018/0020947 A1 · Methods and tools for diagnosing insulin resistance and assessing health status using nmr relaxation times for water > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0020947 A1 - Document ID: US20180020947A1 - Status: Published application - Kind: A1 - Application number: 15/548,442 - Filed: 2016-02-06 - Published: 2018-01-25 - Earliest claimed: 2015-02-06 - Assignees: University of North Texas Health Science Center at Fort Worth - Applicants: University of North Texas Health Science Center At Fort Worth - Inventors: DAVID P. CISTOLA; MICHELLE D. ROBINSON - Web page: https://patentgrep.com/patent/US20180020947A1 ## CPC - A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging - A61B 5/14532: {for measuring glucose, e.g. by tissue impedance measurement} - A61B 5/4866: {Evaluating metabolism (using breath test A61B5/083)} - G01N 24/08: by using nuclear magnetic resonance (G01N24/12 takes precedence) - G01R 33/448: {Relaxometry, i.e. quantification of relaxation times or spin density (G01R33/50 takes precedence)} - G16H 50/30: for calculating health indices; for individual health risk assessment - A61B 5/145: Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value {; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue} (non-radiation detecting or locating of foreign bodies in blood A61B5/06) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract The subject invention pertains to a method that involves at least three steps: (1) acquisition of a NMR data set or spin relaxation curve for plasma, serum or whole blood samples, or for tissues monitored from outside the body, (2) analysis of the NMR data or relaxation curve to extract the T2 and/or T1 relaxation times for water (or surrogates thereof), and (3) conversion of the water T2 and/or T1 values (or surrogates thereof) into a measure of someone's health status (referred to as a T2 or T1 health score depending on the value (T1 or T2 or both T1 and T2) associated with the score). The T1 and/or T2 health score utilizes a statistical database derived from previous studies of subjects ranging from normal, healthy individuals to those having varying degrees of hidden or non-hidden metabolic abnormalities, such as inflammation, insulin resistance, lipid abnormalities (dyslipidemia), oxidative stress, brain abnormalities, cognitive impairment or other disorders, and provides a measure of a subject's overall metabolic and brain health status. ## Claims ### Claim at position 1 1-49. (canceled) ### Claim 50 A method for determining the T2 and/or T1 health score of a subject comprising obtaining a NMR data set or spin relaxation curve for a sample with an NMR or MRI instrument tuned to measure a particular nucleus selected from 1H, 2H, 3H or 17O, analyzing the data or curve to extract T2 and/or T1 relaxation times for water or surrogates thereof and converting the water T2 and/or T1 values into a measure of the health status of the subject (the T2 and/or T1 health score). ### Claim 51 (depends on 50) The method according to claim 50, wherein the sample is a plasma sample, a serum sample, whole blood sample, a tissue sample or a subject, such as a human being. ### Claim 52 (depends on 50) The method according to claim 50, wherein the method comprises a step of partially suppressing the water signal, for example with a 180-degree inversion pulse followed by a delay or any other suitable method for partial suppression of the water signal prior to recording the relaxation curve. ### Claim 53 (depends on 52) The method according to claim 52, wherein the delay time is tuned to eliminate radiation damping while maximizing water signal intensity. ### Claim 54 (depends on 50) The method according to claim 50, wherein the step of analyzing the exponentially decaying or recovering NMR signal comprises acquiring the relaxation curve and subjecting the data to exponential analysis, for example transforming the data with an inverse Laplace transformation, or using any other suitable exponential analysis algorithm. ### Claim 55 (depends on 54) The method according to claim 54, wherein said exponential analysis comprises the analysis of one or more exponential terms, for example one to six exponential terms, two to four exponential terms or three exponential terms. ### Claim 56 (depends on 52) The method according to claim 52, wherein data acquisition begins about 1 to about 50 milliseconds after the start of pulse scheme that acquires the relaxation decay curve; about 16 to about 20 milliseconds after the start of the pulse scheme; or about 19 milliseconds after the start of the pulse scheme ### Claim 57 (depends on 50) The method according to claim 50, wherein said sample is scanned multiple times. ### Claim 58 (depends on 50) The method according to claim 50, wherein the step of converting the T2 and/or T1 values into a measure of the health status of the subject comprises comparing the T2 and/or T1 values obtained for the sample from the subject with T2 and/or T1 values obtained from a database, said database comprising T2 and/or T1 values obtained for a range of subjects, from those who are normal and healthy to those having varying degrees of inflammation, insulin resistance, lipid abnormalities, oxidative stress, brain or cognitive abnormalities and/or other disorders. ### Claim 59 (depends on 50) The method according to claim 50, said method comprising referring an individual subject with a plasma T2 value less than about 800 to a registered dietician, certified personal trainer, physician or other licensed health provider to improve health and well-being, and prevent the onset of diabetes, coronary artery disease, myocardial infarction, ischemic vascular disease, stroke, cognitive impairment, neurodegenerative diseases and dementia, including Alzheimer's disease, or any other diseases that arise from metabolic abnormalities such as chronic, low-grade inflammation, insulin resistance, lipid/lipoprotein abnormalities and/or oxidative stress and/or treating the subject with an appropriate treatment for inflammation, insulin resistance, lipid abnormalities, oxidative stress, brain or cognitive abnormalities and/or other disorders. ### Claim 60 An apparatus for health-screening a subject comprising: a NMR or MRI instrument or portable device tuned to measure a particular nucleus selected from 1H, 2H, 3H or 17O; one or more computer readable storage media; a processing system; a data store contained on the one or more computer readable storage media comprising: one or more reference T2 relaxation times for water and a reference T1 relaxation times for water, for one or more of a sample type, wherein the reference T2 and/or reference T1 values are associated with a health status; program instructions for a health screening service stored on the one or more computer readable storage media that direct the processing system to: acquire an NMR data set, relaxation decay or recovery signal, using the NMR instrument, from a sample of a particular sample type from the subject; analyze the NMR data set or relaxation curve to extract a T2 relaxation time for water and/or a T1 relaxation time for water, or a surrogate of T2 or T1, such as T2* or water peak linewidth; identify the reference values for the particular sample type associated with the extracted T2 and/or T1 values or surrogate values and determine the health status associated with the reference values; and display a health score determined from the health status. ### Claim 61 (depends on 60) The apparatus according to claim 60, wherein the sample type is a whole blood sample, a serum sample, a plasma sample, a tissue sample or a subject, such as a human being. ### Claim 62 (depends on 60) The apparatus according to claim 60, wherein the NMR instrument is a wearable device or is a benchtop or portable time domain NMR instrument or is a NMR spectrometer or magnetic resonance imager. ### Claim 63 An apparatus comprising: one or more computer readable storage media; a processing system; program instructions stored on the one or more computer readable storage media that direct the processing system to: obtain an NMR data set or relaxation decay or recovery curve from a sample obtained from a subject, wherein the data set or relaxation curve was obtained using a NMR instrument tuned to measure a particular nucleus selected from 1H, 2H, 3H or 17O; analyze the NMR data set or relaxation decay curve to extract a T2 relaxation time for water and/or a T1 relaxation time for water or a surrogate of water T2 or T1, such as T2* or water peak linewidth; determine a health status value of the subject, wherein the health status is determined from water T1 and/or T2 values, or surrogates therefor, from the sample; and store the water T2 and/or T1 values, or surrogates therefor, in association with the health status in a data store contained on the one or more computer readable storage media. ### Claim 64 (depends on 50) A method of treating a subject with a plasma water T2 value less than about 800 and at risk for the development of hidden metabolic abnormalities selected from inflammation, insulin resistance, lipid abnormalities (dyslipidemia), oxidative stress, brain abnormalities or other disorders comprising obtaining a health score for a subject according to claim 50 and treating a subject having a health score lower than about 800 for said metabolic abnormality and/or referring said subject to a physician for further evaluation. ### Claim 65 (depends on 64) The method according to claim 64, wherein said hidden metabolic abnormality is low grade inflammation and said subject is further evaluated for treatment with one or more anti-inflammatory agents and/or treated with one or more anti-inflammatory agents. ### Claim 66 (depends on 65) The method according to claim 65, wherein said anti-inflammatory agent is selected from ibuprofen, naproxen, aspirin, celecoxib, sulindac, oxaprozin, salsalate, diflunisal, piroxicam, indomethacin, etodolac, meloxicam, nambumetone, ketorolac tromethamine, or corticosteroids selected from as beclomethasone, beclometasone, budesonide, flunisolide, fluticasone, tramcinolone, methylprednisone, prenisolone or prednisone. ### Claim 67 (depends on 64) The method according to claim 64, wherein said metabolic abnormality is insulin resistance and said subject is further evaluated and/or treated to improve insulin sensitivity, said treatment to improve insulin sensitivity being selected from the start or modification of an exercise and physical activity program, alteration of diet, or other modification of behavior so as to improve insulin sensitivity and reduce the likelihood of developing diabetes arising from insulin resistance. ### Claim 68 (depends on 64) The method according to claim 64, wherein the metabolic abnormality is dyslipidemia and said subject is referred to a physician for further diagnostic evaluation and/or treated with low dose aspirin, statins and/or other lipid-lowering agents. ### Claim 69 (depends on 68) The method according to claim 68, wherein the statin is selected from atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin or simcastatin. ### Claim 70 (depends on 64) The method according to claim 64, wherein the metabolic abnormality is oxidative stress and a subject is referred to a physician and/or registered dietician to receive nutritional advice and/or is evaluated and treated with anti-oxidants such as ascorbic acid (Vitamin C), vitamin E or other nutritional supplements, and/or evaluated and treated for any accompanying inflammation or insulin resistance. ### Claim 71 A method of referring an individual with a plasma water T2 value less than about 800 to a registered dietician, certified personal trainer, physician or other licensed health provider, with the goal to improve health and well-being, and prevent the onset of diabetes, coronary artery disease, myocardial infarction, ischemic vascular disease, stroke, cognitive impairment, neurodegenerative disease and dementia, including Alzheimer's disease, or any other diseases that arise from hidden metabolic abnormalities such as chronic, low-grade inflammation, insulin resistance, lipid/lipoprotein abnormalities, oxidative stress and/or brain abnormalities.