WO2017042635A1 - Système et procédé de détection et de surveillance de trouble de stress post-traumatique (tspt) au moyen de la spectroscopie par résonance magnétique (srm) - Google Patents

Système et procédé de détection et de surveillance de trouble de stress post-traumatique (tspt) au moyen de la spectroscopie par résonance magnétique (srm) Download PDF

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Publication number
WO2017042635A1
WO2017042635A1 PCT/IB2016/001440 IB2016001440W WO2017042635A1 WO 2017042635 A1 WO2017042635 A1 WO 2017042635A1 IB 2016001440 W IB2016001440 W IB 2016001440W WO 2017042635 A1 WO2017042635 A1 WO 2017042635A1
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WIPO (PCT)
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spectral data
ptsd
subject
stress disorder
traumatic stress
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PCT/IB2016/001440
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English (en)
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Carolyn E. Mountford
Scott QUADRELLI
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Translational Research Institute
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Priority to AU2016320637A priority Critical patent/AU2016320637A1/en
Priority to EP16843738.2A priority patent/EP3346919A4/fr
Publication of WO2017042635A1 publication Critical patent/WO2017042635A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/16—Devices for psychotechnics; Testing reaction times ; Devices for evaluating the psychological state
    • A61B5/165—Evaluating the state of mind, e.g. depression, anxiety
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/46—NMR spectroscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/46—NMR spectroscopy
    • G01R33/4633—Sequences for multi-dimensional NMR

Definitions

  • the present invention relates to a system and method for detecting and monitoring PTSD using spectral data obtained using magnetic resonance spectroscopy.
  • PTSD is an increasingly common disorder affecting especially military personnel.
  • the traditional ways of detecting the disorder are by clinical metrics of post-concussion symptom scale, balance error scoring stem and cognitive assessment.
  • Neuropsychological evaluation includes attention related skills, new learning and memory function and intellectual functioning. These detection methods are time consuming, involve some degree of subjectivity and thus possibly misdiagnosis, and are costly.
  • FAAH fatty-acid amide hydrolase
  • a system and method for diagnosing PTSD using spectral data obtained using magnetic resonance spectroscopy.
  • the method comprises acquiring spectral data of a region of the brain of a subject, comparing the acquired spectral data with reference spectral data from normal subjects, and determining whether selected molecules in the obtained spectral data are different relative to the reference spectral data, to indicate that the subject has PTSD.
  • the invention also provides a system for detecting PTSD, and for monitoring the subject and progress of treatment.
  • the selected molecules may be one or more of histidine, fucosylated glycans, lipids, ⁇ - Aminobutyric acid (GAB A), macro molecules (MM), glyceryphosphorylcholine (GPC), Phenylalanine (PE) and glutamate/glutamine.
  • GAB A ⁇ - Aminobutyric acid
  • MM macro molecules
  • GPC glyceryphosphorylcholine
  • PE Phenylalanine
  • glutamate/glutamine glutamate/glutamine
  • the invention provides an effective and relatively objective in vivo method and system for detecting PTSD, noninvasively, in a relatively fast and robust manner which also does not require any communication, counseling or therapy with the subject, thereby reducing the added stress and trauma attendant to the traditional ways of detecting PTSD which remind subjects of the very disorder for which they are seeking treatment.
  • Figure 1 is a three dimensional graph showing 2D COSY data from subjects known to have PTSD;
  • Figure 2 is a table showing the elevated levels of certain molecules from subjects known to have PTSD; and Figure 3 is a three dimensional graph showing levels of fucose in healthy controls (upper) and subjects with PTSD, wherein the fucose I and III are diminished in the PTSD subjects relative to the controls.
  • the present invention provides a method of detecting whether a subject has Post Traumatic Stress Disorder (PTSD) comprising the steps of: acquiring spectral data of the region of a brain of a subject; comparing the acquired spectral data with reference spectral data obtained from normal subjects who have not been diagnosed with PTSD; and determining whether selected molecules in the obtained spectral data differ in concentration relative to the reference spectral data to determine whether the subject has PTSD based on the comparison.
  • PTSD Post Traumatic Stress Disorder
  • the selected molecules may comprise at least one of histidine, fucosylated glycans, lipids, ⁇ - Aminobutyric acid (GAB A), macro molecules (MM), glyceryphosphorylcholine (GPC), Phenylalanine (PE) and glutamate/glutamine.
  • the acquired spectral data may be L-COSY 2D spectral data.
  • the method may further comprise repeating the steps of acquiring, comparing and determining while the subject is undergoing treatment for PTSD, to determine the progress of treatment.
  • the invention also provides a system for detecting whether a subject has Post Traumatic Stress Disorder (PTSD) comprising: a spectrometer acquiring spectral data of the region of a brain of a subject; a comparator for comparing the acquired spectral data with reference spectral data obtained from normal subjects who have not been diagnosed with PTSD; and a processor for determining whether selected molecules in the obtained spectral data differ in concentration relative to the reference spectral data to determine whether the subject has PTSD based on the comparison.
  • the selected molecules may comprise at least one of histidine, fucosylated glycans, lipids, ⁇ - Aminobutyric acid (GAB A), macro molecules (MM), glyceryphosphorylcholine (GPC),
  • the acquired spectral data may be COSY 2D spectral data.
  • the system may comprise a memory for storing spectral data obtained from a subject from at least two different time periods, and wherein the processor compares two differently obtained spectral data to determine whether the subject is responding favorably to treatment.
  • Subjects who have been diagnosed with PTSD using conventional psychological methods can be used to develop a reference database by having their brains scanned with an MR spectrometer separate or as part of a clinical MRI scanner of a magnetic resonance spectroscopy system.
  • the system can be a 3Tesla (3T) or higher MRI scanner using a 32 or 64 or greater channel head coil.
  • the pulse sequence used may be an L-COSY either ID or 2D. Further details on how to acquire such data may be found in Ramadan S. et al., In Vivo Two Dimensional MR Spectroscopy Compares the Biochemistry of the Human Brain and Glioblastoma, and Radiology, 2011.
  • the spectral data from normal subjects will comprise a reference database in which certain molecules will have certain reference concentrations.
  • Subjects known to have PTSD by conventional diagnostic methods have been found to have different concentration of certain molecules in their brain compared to normal subjects.
  • Figure 2 comprises a Table of concentrations of certain molecules of PTSD subjects and how they differ from controls who are normal subjects. The last column of the Table shows the % difference of the molecule concentrations of the PTSD subjects relative to normal control subjects. The changes include but are not limited to those in Table 1 plus the fucosylated glycerns including Fuel and Fuc 4.
  • a subject to be evaluated for possible PTSD will undergo magnetic resonance spectroscopy of the brain to obtain the molecular concentration or ratio of the molecules listed and possibly other telltale marker molecules.
  • a determination can be made on whether the suspected subject has PTSD in an efficient and robust manner.
  • the comparison may also be made using a classifier method developed from a database.
  • Figures 1 and 3 show three dimensional results of spectra from a subject diagnosed with PTSD, and showing different concentrations of certain molecules relative to normal controls.
  • Classifiers may be developed for automated diagnosis if desired, instead of or in addition to manual diagnosis.
  • Diffuse axonal injury (DAI) from PTSD can arise from at least 10 different types of measurable deregulation or damage.
  • 2D COSY provides specific DAI chemical changes providing a non-invasive and objective diagnosis more robust than conventional diagnosis methods.
  • the invention also includes treatment methods and monitoring to determine progress of subjects in treating the disorder.
  • Personalized treatment approaches can be employed, as the diagnosis method reveals the precise chemical imbalances that need correction. For example, if the diagnosis result indicates inflammation, the condition can be treated with anti-inflammatory medications or other treatment, and periodically monitored by testing the subject to determine the rate of recovery.
  • Targeted intervention will provide early response with benefit in long-term neuropsychological and neuropsychiatric outcomes.

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  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Biophysics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • High Energy & Nuclear Physics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Psychiatry (AREA)
  • Social Psychology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Developmental Disabilities (AREA)
  • Educational Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un système et un procédé qui identifient un trouble de stress post-traumatique au moyen de la spectroscopie par résonance magnétique (SRM) afin de mesurer les concentrations absolues et relatives de métabolites dans des régions spécifiques du cerveau dans le système nerveux central ou le cerveau. Le système et le procédé peuvent être utilisés en tant qu'outil de diagnostic pour l'évaluation d'un TSPT. Ces changements chimiques dans le cerveau des personnes souffrant de TSPT sont différents de celles souffrant de lésion crânienne, douleur chronique et d'autres états neurologiques.
PCT/IB2016/001440 2015-09-10 2016-09-12 Système et procédé de détection et de surveillance de trouble de stress post-traumatique (tspt) au moyen de la spectroscopie par résonance magnétique (srm) WO2017042635A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2016320637A AU2016320637A1 (en) 2015-09-10 2016-09-12 System and method for detecting and monitoring Post Traumatic Stress Disorder (PTSD) using magnetic resonance spectroscopy (MRS)
EP16843738.2A EP3346919A4 (fr) 2015-09-10 2016-09-12 Système et procédé de détection et de surveillance de trouble de stress post-traumatique (tspt) au moyen de la spectroscopie par résonance magnétique (srm)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562216947P 2015-09-10 2015-09-10
US62/216,947 2015-09-10
US201562217484P 2015-09-11 2015-09-11
US62/217,484 2015-09-11

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WO2017042635A1 true WO2017042635A1 (fr) 2017-03-16

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AU (1) AU2016320637A1 (fr)
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019043648A1 (fr) * 2017-09-01 2019-03-07 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Système et procédé de détection et de surveillance de l'exposition au souffle à l'aide de spectroscopie par résonance magnétique (srm)
EP3598940A1 (fr) * 2018-07-25 2020-01-29 The Charles Stark Draper Laboratory, Inc. Procédé et système pour le diagnostic du trouble de stress post-traumatique (tspt) et du traumatisme cérébral léger (mtbi) à l'aide d'une spectroscopie par résonance magnétique
WO2020026150A1 (fr) * 2018-07-30 2020-02-06 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Procédé et système de détection et d'identification d'une réponse à un stress aigu suite à l'exposition à un traumatisme, de sa transition vers un trouble de stress post-traumatique, et de surveillance d'une thérapie ultérieure
WO2020084535A1 (fr) * 2018-10-24 2020-04-30 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Procédé et système de surveillance de la progression du traitement d'un individu présentant une douleur aiguë, une douleur chronique, un trouble de stress aigu, une exposition au souffle ou un ptsd à l'aide de données spectrales du cerveau
WO2020121175A1 (fr) * 2018-12-10 2020-06-18 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Système et méthode de détection et de surveillance de niveaux de douleur à l'aide de la spectroscopie par résonance magnétique (srm)
WO2020165870A1 (fr) * 2019-02-15 2020-08-20 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Système et procédé de traitement et de surveillance de trouble de stress post-traumatique (tspt)

Citations (1)

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WO2015027116A1 (fr) 2013-08-21 2015-02-26 The Regents Of The University Of California Motifs de métabolites pour le diagnostic et la prédiction de troubles affectant le cerveau et le système nerveux

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EP2642919A4 (fr) * 2010-11-26 2014-10-08 Brigham & Womens Hospital Procédé d'évaluation de lésions traumatiques de la tête répétitives à l'aide de spectroscopie de résonance magnétique bidimensionnelle

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Publication number Priority date Publication date Assignee Title
WO2015027116A1 (fr) 2013-08-21 2015-02-26 The Regents Of The University Of California Motifs de métabolites pour le diagnostic et la prédiction de troubles affectant le cerveau et le système nerveux

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HAM B-J ET AL.: "DECREASED N-ACETYL-ASPARTATE LEVELS IN ANTERIOR CINGULATE AND HIPPOCAMPUS IN SUBJECTS WITH POST-TRAUMATIC STRESS DISORDER: A PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDY", EUROPEAN JOURNAL OF NEUROSCIENCE, vol. 25, no. 1, 12 January 2007 (2007-01-12), pages 324 - 329, XP055518611 *
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YANG Z-Y ET AL.: "PROTON MAGNETIC RESONANCE SPECTROSCOPY REVEALED DIFFERENCES IN THE GLUTAMATE+GLUTAMINE/CREATINE RATIO OF THE ANTERIOR CINGULATE CORTEX BETWEEN HEALTHY AND PEDIATRIC POST-TRAUMATIC STRESS DISORDER PATIENTS DIAGNOSED AFTER 2008 WENCHUAN EARTHQUAKE", PSYCHIATRY AND CLINICAL NEUROSCIENCES, vol. 69, no. 12, 2015, pages 782 - 790, XP055518607 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019043648A1 (fr) * 2017-09-01 2019-03-07 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Système et procédé de détection et de surveillance de l'exposition au souffle à l'aide de spectroscopie par résonance magnétique (srm)
EP3598940A1 (fr) * 2018-07-25 2020-01-29 The Charles Stark Draper Laboratory, Inc. Procédé et système pour le diagnostic du trouble de stress post-traumatique (tspt) et du traumatisme cérébral léger (mtbi) à l'aide d'une spectroscopie par résonance magnétique
US11529054B2 (en) 2018-07-25 2022-12-20 The Charles Stark Draper Laboratory, Inc. Method and system for post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) diagnosis using magnetic resonance spectroscopy
WO2020026150A1 (fr) * 2018-07-30 2020-02-06 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Procédé et système de détection et d'identification d'une réponse à un stress aigu suite à l'exposition à un traumatisme, de sa transition vers un trouble de stress post-traumatique, et de surveillance d'une thérapie ultérieure
WO2020084535A1 (fr) * 2018-10-24 2020-04-30 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Procédé et système de surveillance de la progression du traitement d'un individu présentant une douleur aiguë, une douleur chronique, un trouble de stress aigu, une exposition au souffle ou un ptsd à l'aide de données spectrales du cerveau
WO2020121175A1 (fr) * 2018-12-10 2020-06-18 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Système et méthode de détection et de surveillance de niveaux de douleur à l'aide de la spectroscopie par résonance magnétique (srm)
WO2020165870A1 (fr) * 2019-02-15 2020-08-20 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust Système et procédé de traitement et de surveillance de trouble de stress post-traumatique (tspt)
US20200261012A1 (en) * 2019-02-15 2020-08-20 Translational Research Institute Pty Ltd As Trustee For Translational Research Institute Trust System and method for treating and monitoring post traumatic stress disorder (ptsd)

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EP3346919A1 (fr) 2018-07-18
AU2016320637A1 (en) 2018-04-26

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