# US 2014/0154185 A1 · Use of non-labeled sugars and detection by mri for assessing tissue perfusion and metabolism > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154185 A1 - Document ID: US20140154185A1 - Status: Published application - Kind: A1 - Application number: 13/994,600 - Filed: 2011-12-14 - Published: 2014-06-05 - Earliest claimed: 2010-12-14 - Assignees: The Johns Hopkins University - Inventors: Peter C. Van Zijl; Dmitri Artemov; Kannie Wai Yan Chan; Yoshinori Kato; Michael T. McMahon; Guanshu Liu - Web page: https://patentgrep.com/patent/US20140154185A1 ## CPC - A61K 49/10: Organic compounds - A61B 5/026: Measuring blood flow {(A61B3/1233, A61B3/1241 take precedence)} - 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 5/14539: {for measuring pH} - A61B 5/4866: {Evaluating metabolism (using breath test A61B5/083)} - A61B 5/74: {Details of notification to user or communication with user or patient; User input means} - A61M 5/142: Pressure infusion, e.g. using pumps - G01R 33/5605: {by transferring coherence or polarization from a spin species to another, e.g. creating magnetization transfer contrast [MTC], polarization transfer using nuclear Overhauser enhancement [NOE]} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12) ## Abstract A method for magnetic resonance (MR) imaging or spectroscopy on a MR scanner to detect tissue physiological parameters in one or more tissue areas in a human or non-human subject includes administering to the subject a contrast enhancing physiologically tolerable amount of a sugar that is non-labeled, subjecting the subject to an MR procedure capable of generating MR signals encoding at least one tissue area in the subject in which the sugar either passes or is taken up, detecting a temporal variation in the MR signals in the at least one tissue area after the administering the sugar, determining at least one tissue-related parameter from the temporal variation, and ascertaining whether the at least one tissue-related parameter is abnormal. ## Claims ### Claim 1 A method for magnetic resonance (MR) imaging or spectroscopy on a MR scanner to detect tissue physiological parameters in one or more tissue areas in a human or non-human subject, comprising: administering to said subject a contrast enhancing physiologically tolerable amount of a sugar that is non-labeled; subjecting said subject to an MR procedure capable of generating MR signals encoding at least one tissue area in said subject in which said sugar either passes or is taken up; detecting a temporal variation in said MR signals in said at least one tissue area after said administering said sugar; determining at least one tissue-related parameter from said temporal variation; and ascertaining whether said at least one tissue-related parameter is abnormal. ### Claim 2 (depends on 1) A method according to claim 1, wherein said at least one tissue-related parameter comprises at least one of a sugar uptake, a sugar metabolism or pass-through speed, a perfusion parameter, a blood volume, a pH, or a permeability parameter. ### Claim 3 (depends on 2) A method according to claim 2, wherein said abnormality comprises at least one of a cancer, a vascular disease, an ischemia, a tissue degeneration, a tissue inflammation, or an infection. ### Claim 4 (depends on 1) A method according to claim 1, wherein said at least one tissue area comprises one of a brain, an esophagus, a breast, a pancreas, a small intestine, a colon, a lung, a rectum, a liver, a kidney, a prostate, a uterus, a testicle, a muscle, a joint, a spine, or a bone. ### Claim 5 (depends on 1) A method according to claim 1, wherein said administering comprises an intravenous administration of a sugar solution. ### Claim 6 (depends on 5) A method according to claim 5, wherein said intravenous administration employs a bolus, an infusion of controllable adjustable rate, or combinations thereof. ### Claim 7 (depends on 5) A method according to claim 5, wherein said intravenous administration is through an external device or an embedded applicator. ### Claim 8 (depends on 1) A method according to claim 1, wherein said administering comprises an oral administration of ingestible sugar. ### Claim 9 (depends on 1) A method according to claim 1, wherein said sugar is at least one of a synthetic or naturally occurring sugar, including D-glucose or L-glucose, its polymers or any other biocompatible sugar containing one or more hydroxyl groups or other exchangeable groups and their isomers. ### Claim 10 (depends on 1) A method according to claim 1, wherein said MR procedure is adapted to detect proton exchange transfer in said at least one tissue area of said subject caused by said administering of said sugar. ### Claim 11 (depends on 10) A method according to claim 10, wherein said MR procedure comprises a MR imaging (MRI) or MR spectroscopy (MRS) technique capable of: providing a selective saturation or a frequency labeling of one or more exchangeable groups of a sugar molecule; and subsequently detecting water MR signals corresponding to said at least one of said exchangeable groups. ### Claim 12 (depends on 10) A method according to claim 10, wherein said MR procedure comprises a MR imaging (MRI) or MR spectroscopy (MRS) technique capable of measuring changes in water MR signal based on a changed water relaxation rate caused by said sugar having said one or more exchangeable groups. ### Claim 13 (depends on 11) A method according to claim 11, wherein the water MR signals are recorded with stock MRI or MRS sequences available on a MR scanner. ### Claim 14 (depends on 11) A method according to claim 11, wherein all of said exchangeable groups are utilized to enhance a detection sensitivity metric. ### Claim 15 (depends on 11) A method according to claim 11, wherein at least one of said exchangeable groups is utilized to sensitize said estimating one of said tissue-related parameters. ### Claim 16 (depends on 11) A method according to claim 11, wherein at least one of said exchangeable groups is utilized to enhance said detecting of said temporal variation in MR signals. ### Claim 17 (depends on 1) A method of claim 1, wherein said physiological parameters comprise at least one of a steady state metric or a dynamic metric. ### Claim 18 (depends on 1) A method of claim 1, wherein said ascertaining comprises a pharmacokinetics analysis to ascertain said tissue-related parameter. ### Claim 19 (depends on 18) A method of claim 18, wherein said determining further comprises measuring said subject's blood glucose level to form a blood input function and incorporating said input function into said pharmacokinetics analysis. ### Claim 20 A method for magnetic resonance (MR) imaging or spectroscopy on a MR scanner, comprising: generating a first recorded MR signal by observing a tissue area of a subject under observation in a magnet adapted to provide a characteristic main magnetic field with a corresponding characteristic water proton resonant frequency; generating a second recorded MR signal by repeating said observing at a later time when the subject's blood sugar level is elevated; detecting a difference between the second recorded MR signal and the first recorded MR signal; and subsequently ascertaining a physiological parameter associated with said tissue area of said subject under observation based on the detected difference. ### Claim 21 (depends on 20) A method according to claim 20, further comprising administering sugar to said subject to cause said subject's blood sugar level to become elevated. ### Claim 22 (depends on 21) A method according to claim 21, wherein said generating said first recorded MR signal is performed prior to said administering and said generating said second recorded MR signal is performed during said administering. ### Claim 23 (depends on 21) A method according to claim 21, wherein said generating said first recorded MR signal is performed during said administering and said generating said second recorded MR signal is performed after said administering has been stopped. ### Claim 24 (depends on 21) A method according to claim 21, further comprising generating a plurality of recorded MR signal prior to, during, and after said administering. ### Claim 25 (depends on 20) A method according to claim 20, wherein said physiologic parameters comprise at least one of a sugar uptake, a sugar metabolism or pass-through speed, a perfusion parameter, a blood volume, a pH, or a permeability parameter. ### Claim 26 (depends on 20) A method according to claim 20, wherein said MR scanner is adapted to provide a selective saturation or a frequency labeling of at least one exchangeable groups of a sugar molecule. ### Claim 27 (depends on 20) A method according to claim 20, wherein said MR scanner is adapted for measuring changes in water MR signal based on a changed water relaxation rate caused by said sugar having one or more exchangeable groups. ### Claim 28 (depends on 1) A method of claim 1, wherein said ascertaining comprises a pharmacokinetics analysis. ### Claim 29 (depends on 28) A method of claim 28, further comprising incorporating an input function into said pharmacokinetics analysis. ### Claim 30 (depends on 20) A computer-readable medium comprising software instructions, which software instructions when executed by a computer, causes the computer, in conjunction with said MR scanner, to implement the method of claim 20. ### Claim 31 A toolkit for imaging a subject in a MR system, comprising: a MR-compatible external device constructed to inject a biocompatible dose of sugar in said subject under observation in said MR system; and a sugar analyzer configured to measure blood glucose levels in said subject before, during, and after said dose of glucose is injected into said subject. ### Claim 32 (depends on 31) A toolkit of claim 31, wherein said external device comprises an infusion pump capable of being synchronized with data acquisition on said MR system. ### Claim 33 (depends on 32) A toolkit of claim 32, further comprising: a computing engine in communication with said MR system and said sugar analyzer, said computing engine programmed to: receive at least one of: measured data from said MR system or measured blood glucose levels from said sugar analyzer, said measured data comprising MR signal changes caused by an injection of said dose of sugar into said subject; compute a physiologic parameter based on at least one of: said measured data or said measured blood sugar levels, said physiologic parameter comprising: a perfusion parameter or a metabolism parameter; and output said physiologic parameter to a user. ### Claim 34 (depends on 31) A toolkit of claim 31, wherein said physiologic parameter comprises one of: a standard uptake value, a metabolic parameter, a permeability parameter, a tissue mean transit time, a tissue blood volume, a tissue blood flow, or a pH.