AU2018326834A1 - System and method for detecting and monitoring blast exposure using magnetic resonance spectroscopy (MRS) - Google Patents
System and method for detecting and monitoring blast exposure using magnetic resonance spectroscopy (MRS) Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
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- A61B5/0042—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the brain
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- A—HUMAN NECESSITIES
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- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
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- A61B5/4064—Evaluating the brain
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- A61B5/40—Detecting, measuring or recording for evaluating the nervous system
- A61B5/4076—Diagnosing or monitoring particular conditions of the nervous system
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- 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]
- G01R33/48—NMR imaging systems
- G01R33/483—NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
- G01R33/485—NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy based on chemical shift information [CSI] or spectroscopic imaging, e.g. to acquire the spatial distributions of metabolites
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
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- A61B5/48—Other medical applications
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- 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
- G01R33/4625—Processing of acquired signals, e.g. elimination of phase errors, baseline fitting, chemometric analysis
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- 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
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- 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]
- G01R33/48—NMR imaging systems
- G01R33/483—NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
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Abstract
A system and method identifies blast exposure by the use of magnetic resonance spectroscopy (MRS) to measure absolute and relative concentrations of metabolites in specific brain regions in the central nervous system or brain. The system and method can be used as a diagnostic tool for the assessment of blast exposure. These chemical changes in the brain of those people suffering from blast exposure are different from those suffering from head injury, chronic pain and other neurological conditions.
Description
SYSTEM AND METHOD FOR DETECTING AND MONITORING BLAST EXPOSURE USING
MAGNETIC RESONANCE SPECTROSCOPY (MRS)
BACKGROUND OF THE INVENTION
The present invention relates to a system and method for detecting and monitoring blast exposure using spectral data obtained using magnetic resonance spectroscopy.
Within this patent application are certain reference citations. These citations are incorporated herein by reference.
Blast exposure is an increasingly common disorder affecting especially military personnel. Blast exposure soldiers have not shown detectable structural brain abnormalities on MRI images, SWI or FLAIR.
SUMMARY OF THE INVENTION
It has been determined that the medical condition of blast exposure has neurological impact on a subject. Blast exposure has a distinctive neurological pattern, and the level of blast exposure is measureable using magnetic resonance spectroscopy (MRS).
In accordance with the present invention, a system and method are provided for diagnosing blast exposure using spectral data obtained using MRS. 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 blast exposure.
The invention also provides a system for detecting blast exposure, and for monitoring the subject and progress of treatment.
The selected molecules may be one or more of NAA, Phenylalanine (PE), total fructose, afucose, fucosylated glycans III, and Myo-Inos + Cr.
The invention provides an effective and relatively objective in vivo method and system for detecting blast exposure, noninvasively, in a relatively fast and robust manner which also does
WO 2019/043648
PCT/IB2018/056683 not require any communication, counseling or therapy with the subject, thereby reducing the added stress and trauma attendant to the traditional ways of detecting blast exposure which remind subjects of the very disorder for which they are seeking treatment.
Other advantages will be apparent from the following description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a graph showing the % difference in detected concentration of certain neurochemicals of blast exposed soldiers and police with post traumatic stress disorder (PTSD) compared to civilian control subjects;
Figure 2 is a graph showing the % difference in detected concentrations of certain neurochemicals of breachers and artillery exposed subjects, and subjects with repetitive head injuries, compared to civilian control subjects; and
Figure 3 is a block diagram of a system having a spectrometer, comparator and processor.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A preferred embodiment of the invention will be disclosed, but the invention will not be limited to this embodiment.
The present invention provides a method of detecting whether a subject has blast exposure 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 blast exposure; 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 blast exposure based on the comparison. The reference spectral data can be reference spectral data for subjects known to have blast exposure through other diagnosis, wherein the obtained spectral data is compared to the reference spectral data for known blast exposure subjects to see if a similarity exists.
WO 2019/043648
PCT/IB2018/056683
The selected molecules may comprise at least one of the neurochemicals described above.. 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 blast exposure, to determine the progress of treatment.
The invention also provides a system for detecting whether a subject has blast exposure 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 blast exposure; 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 blast exposure based on the comparison. The system may in the alternative compare the obtained spectral data with referenced spectral data for subjects known to have blast exposure through other diagnosis, to see if a similarity exists.
The selected molecules may comprise at least one of the neurochemicals described above. 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 blast exposure 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. 259(2): p. 540-9 and Mountford, C., et al. Six fucose-alpha(l-2) sugars and alpha-fucose
WO 2019/043648
PCT/IB2018/056683 assigned in the human brain using in vivo two-dimensional MRS. NMR Biomed, 2015. 28(3): p. 291-6.
The spectral data from normal subjects will comprise a reference database in which certain molecules will have certain reference concentrations. Subjects known to have blast exposure by conventional diagnostic methods have been found to have different concentration of certain molecules in their brain compared to normal or control subjects.
Figures 1 and 2 are graphs of concentrations of certain molecules of blast control subjects and how they differ from controls who are normal subjects.
» PhehylWftias by·* 22¾ s &05) * Tstst Fucose by «'Fiiesse: decreased by 37¾ • by 22¾ • fetyisAflsc+Qs’ eassgttfey 14¾ * Three stta unass^ued depressed fey 23. ?S arid 42%
These graphs show that the concentrations of selected neurochemicals of subjects having blast exposure differ significantly from those in normal or control subjects.
A subject to be evaluated for possible blast exposure will undergo magnetic resonance spectroscopy of the brain to obtain the molecular concentration or ration of the molecules listed and possibly other telltale marker molecules. By comparing the results with the reference molecule concentrations or ratios, a determination can be made on whether the suspected subject
WO 2019/043648
PCT/IB2018/056683 has blast exposure in an efficient and robust manner. The comparison may also be made using a classifier method developed from a database.
The changes may differ depending on the region of the brain being examined. Classifiers may be developed for automated diagnosis if desired, instead of or in addition to manual diagnosis.
Diffuse axonal injury (DAI) from blast exposure can arise from 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.
Although one embodiment has been described, the invention is not limited to this embodiment and variations may occur to those skilled in the art. The scope is limited only by way of the claims.
Claims (8)
1. A method of detecting whether a subject has blast exposure comprising the steps of: acquiring spectral data of the region of a brain of a subject;
comparing the acquired spectral data reference spectral data obtained from one of (i) normal subjects who have not been diagnosed with blast exposure, and (ii) subjects known to have blast exposure; and determining whether selected molecules in the obtained spectral data differ or are similar in concentration relative to the reference spectral data to determine whether the subject has blast exposure based on the comparison.
2. The method of claim 1, wherein the selected molecules comprise at least one of NAA, Phenylalanine (PE), total fructose, α-fucose, fucosylated glycans III, and Myo-Inos + Cr.
3. The method of claim 1, wherein the acquired spectral data is COSY 2D spectral data.
4. The method of claim 1, further comprising repeating the steps of acquiring, comparing and determining while the subject is undergoing treatment for blast exposure, to determine the progress of treatment.
5. A system for detecting whether a subject has blast exposure 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 one of: (i) normal subjects who have not been diagnosed with blast exposure, and (ii) subjects known to have blast exposure; and a processor for determining whether selected molecules in the obtained spectral data differ or are similar in concentration relative to the reference spectral data to determine whether the subject has PTSD based on the comparison.
WO 2019/043648
PCT/IB2018/056683
6. The system of claim 5, wherein the selected molecules comprise at least one of NAA, Phenylalanine (PE), total fructose, α-fucose, fucosylated glycans III, and Myo-Inos + Cr.
7. The system of claim 5, wherein the acquired spectral data is COSY 2D spectral data.
8. The system of claim 5, further comprising 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.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762553502P | 2017-09-01 | 2017-09-01 | |
| US62/553,502 | 2017-09-01 | ||
| PCT/IB2018/056683 WO2019043648A1 (en) | 2017-09-01 | 2018-08-31 | System and method for detecting and monitoring blast exposure using magnetic resonance spectroscopy (mrs) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2018326834A1 true AU2018326834A1 (en) | 2020-03-05 |
| AU2018326834A8 AU2018326834A8 (en) | 2022-02-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018326834A Pending AU2018326834A1 (en) | 2017-09-01 | 2018-08-31 | System and method for detecting and monitoring blast exposure using magnetic resonance spectroscopy (MRS) |
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| Country | Link |
|---|---|
| EP (1) | EP3675728A4 (en) |
| AU (1) | AU2018326834A1 (en) |
| WO (1) | WO2019043648A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3870031A4 (en) * | 2018-10-24 | 2022-07-27 | Datchem Pty Ltd | Method and system for monitoring the progress of treatment of an individual having acute pain, chronic pain, acute stress disorder, blast exposure or ptsd using spectral data of the brain |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1949123A2 (en) * | 2005-10-18 | 2008-07-30 | Cambridge Enterprise Limited | Methods and biomarkers for diagnosing and monitoring psychotic disorders |
| US20090247860A1 (en) * | 2007-10-25 | 2009-10-01 | Research Foundation Of State University Of New York | Spectral biomarker and algorithm for the identification and detection of neural stem and progenitor cells and their use in studying mammalian brains |
| EP2642919A4 (en) * | 2010-11-26 | 2014-10-08 | Brigham & Womens Hospital | Method for assessing repetitive head injuries with tow-dimensional magnetic resonance spectorscopy |
| WO2015171870A1 (en) * | 2014-05-07 | 2015-11-12 | University Of Utah Research Foundation | Diagnosis of affective disorders using magnetic resonance spectroscopy neuroimaging |
| US20160377639A1 (en) * | 2015-06-27 | 2016-12-29 | William Beaumont Hospital | Methods for detecting, diagnosing and treating traumatic brain injury |
| AU2016320637A1 (en) * | 2015-09-10 | 2018-04-26 | Translational Research Institute | System and method for detecting and monitoring Post Traumatic Stress Disorder (PTSD) using magnetic resonance spectroscopy (MRS) |
-
2018
- 2018-08-31 EP EP18851200.8A patent/EP3675728A4/en not_active Withdrawn
- 2018-08-31 WO PCT/IB2018/056683 patent/WO2019043648A1/en unknown
- 2018-08-31 AU AU2018326834A patent/AU2018326834A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2018326834A8 (en) | 2022-02-17 |
| EP3675728A4 (en) | 2021-05-19 |
| EP3675728A1 (en) | 2020-07-08 |
| WO2019043648A1 (en) | 2019-03-07 |
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